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Biomedical subjects

Xia Li

Publications and source records attributed to Xia Li.

At least 91 records · Page 5Linked to original sources

The beta-adrenergic blocker carvedilol restores L-type calcium current in a myocardial infarction model of rabbit.

BACKGROUND: Carvedilol, an antagonist of alpha1- and beta-adrenergic receptors, has shown efficacy in reducing all-cause death and arrhythmia death for ischemic heart disease and congestive heart failure in several large-scale trials. It has been found to prevent ventricular remodeling, and recently was reported to reverse down-regulation of Na+ channel in a chronic heart failure model. This study was conducted to investigate whether carvedilol could reverse the ion remodeling in a myocardial infarction model of rabbit. METHODS: After the procedure of coronary ligation, animals were randomized to placebo or carvedilol treatment (5 mg/kg). Action potentials, L-type calcium current (Ica L) and the effect of isoproterenol stimulation on Ica L were measured using whole-cell patch method. Evaluation of the expression of calcium channel subunits was carried out by RT-PCR and Western blot. RESULTS: The results indicate that mean peak Ica L densities (pA/pF) at +10 mV was reduced in postinfarction myocytes (5.33 +/- 0.45, n = 25) compared to sham myocytes (6.52 +/- 0.21, n = 20). Treatment of myocardial infarction rabbits with carvedilol could restore it partially (5.91 +/- 0.39, n = 20, P < 0.05). However, steady-state activation parameters were similar in three groups. With stimulation by isoproterenol (1 micromol/L) Ica L increased in all three groups, but the increase was smaller in postinfarction myocytes. mRNA levels of calcium channel subunit CaA1 gene was decreased but CaB2a, CaB2b and CaB3 mRNA levels did not change after MI. Corresponding change in CaA1 protein was also observed. CONCLUSIONS: The results demonstrate that carvedilol restores Ica L density and reverse the downregulation of CaA1 postinfarction.

Action Potentials↗

No relationship between sequence variation in protein coding regions of the Tas1r3 gene and saccharin preference in rats.

Nearly all mammalian species like sweet-tasting foods and drinks, but there are differences in the degree of 'sweet tooth' both between species and among individuals of the same species. Some individual differences can be explained by genetic variability. Polymorphisms in a sweet taste receptor (Tas1r3) account for a large fraction of the differences in consumption of sweet solutions among inbred mouse strains. We wondered whether mice and rats share the same Tas1r3 alleles, and whether this gene might explain the large difference in saccharin preference among rats. We conducted three experiments to test this. We examined DNA sequence differences in the Tas1r3 gene among rats that differed in their consumption of saccharin in two-bottle choice tests. The animals tested were from an outbred strain (Sprague-Dawley; experiment 1), selectively bred to be high- or low-saccharin consumers (HiS and LoS; experiment 2), or from inbred strains with established differences in saccharin preference (FH/Wjd and ACI; experiment 3). Although there was considerable variation in saccharin preference among the rats there was no variation in the protein-coding regions of the Tas1r3 gene. DNA variants in intronic regions were detected in 1 (of 12) outbred rat with lower-than-average saccharin preference and in the ACI inbred strain, which also has a lower saccharin preference than the FH/Wjd inbred partner strain. Possible effects of these intronic nucleotide variants on Tas1r3 gene expression or the presence of T1R3 protein in taste papillae were evaluated in the ACI and FH/Wjd strains. Based upon the results of these studies, we conclude that polymorphisms in the protein-coding regions of the sweet receptor gene Tas1r3 are uncommon and do not account for individual differences in saccharin preference for these strains of rats. DNA variants in intron 4 and 5 are more common but appear to be innocuous.

Animals↗

NMR characterization of the Escherichia coli nitrogen regulatory protein IIANtr in solution and interaction with its partner protein, NPr.

The solution form of IIA(Ntr) from Escherichia coli and its interaction with its partner protein, NPr, were characterized by nuclear magnetic resonance (NMR) spectroscopy. The diffusion coefficient of the protein (1.13 x 10(-6) cm/sec) falls between that of HPr (approximately 9 kDa) and the N-terminal domain of E. coli enzyme I (approximately 30 kDa), indicating that the functional form of IIA(Ntr) is a monomer (approximately 18 kDa) in solution. Thus, the dimeric structure of the protein found in the crystal is an artifact of crystal packing. The residual dipolar coupling data of IIA(Ntr) (covering residues 11-155) measured in the absence and presence of a 4% polyethyleneglycol-hexanol liquid crystal alignment medium fit well to the coordinates of both molecule A and molecule B of the dimeric crystal structure, indicating that the 3D structures in solution and in the crystal are indeed similar for that protein region. However, only molecule A possesses an N-terminal helix identical to that derived from chemical shifts of IIA(Ntr) in solution. Further, the (15)N heteronuclear nuclear Overhauser effect (NOE) data also support molecule A as the representative structure in solution, with the terminal residues 1-8 and 158-163 more mobile. Chemical shift mapping identified the surface on IIA(Ntr) for NPr binding. Residues Gly61, Asp115, Ser125, Thr156, and nearby regions of IIA(Ntr) are more perturbed and participate in interaction with NPr. The active-site His73 of IIA(Ntr) for phosphoryl transfer was found in the Ndelta1-H tautomeric state. This work lays the foundation for future structure and function studies of the signal transducing proteins from this nitrogen pathway.

Carrier Proteins↗

Dehydration anorexia is attenuated in oxytocin-deficient mice.

Evidence in rats suggests that central oxytocin (OT) signaling pathways contribute to suppression of food intake during dehydration (i.e., dehydration anorexia). The present study examined water deprivation-induced dehydration anorexia in wild-type and OT -/- mice. Mice were deprived of food alone (fasted, euhydrated) or were deprived of both food and water (fasted, dehydrated) for 18 h overnight. Fasted wild-type mice consumed significantly less chow during a 60-min refeeding period when dehydrated compared with their intake when euhydrated. Conversely, fasting-induced food intake was slightly but not significantly suppressed by dehydration in OT -/- mice, evidence for attenuated dehydration anorexia. In a separate experiment, mice were deprived of water (but not food) overnight for 18 h; then they were anesthetized and perfused with fixative for immunocytochemical analysis of central Fos expression. Fos was elevated similarly in osmo- and volume-sensitive regions of the basal forebrain and hypothalamus in wild-type and OT -/- mice after water deprivation. OT-positive neurons expressed Fos in dehydrated wild-type mice, and vasopressin-positive neurons were activated to a similar extent in wild-type and OT -/- mice. Conversely, significantly fewer neurons within the hindbrain dorsal vagal complex were activated in OT -/- mice after water deprivation compared with activation in wild-type mice. These findings support the view that OT-containing projections from the hypothalamus to the hindbrain are necessary for the full expression of compensatory behavioral and physiological responses to dehydration.

Animals↗

[Proliferation of type II collagen specific T cell response and antibody formation in rheumatoid arthritis and their relations to HLA-DR4].

OBJECTIVE: To investigate the proliferation of type II collagen specific T cell response and antibody formation in rheumatoid arthritis (RA) and their relations to HLA-DR4 subtype. METHODS: Peripheral blood mononuclear cells and serum were obtained from 62 RA patients, 14 males and 48 females, aged 43 +/- 29. CII263-272 decapeptide and the peripheral blood mononuclear cells (PBMCs) from 62 RA patients were co-incubated for 5 approximately 7 days. MTT method was used to examine the T cell proliferation. The serum antibodies specific to CII 263-272 were examined by ELISA. HLA-DR typing was detected in 40 patients by SSP-PCR. RESULTS: Positive T cell response challenged by CII 263-272 decapeptide was observed in 38 (61.3%) RA patients. The positive rate of CII 263-272 antibody was 66.7% in the T cell response positive group, significantly higher than that of the T cell response negative group (34.6%, P < 0.05). The T cell response rate of the CII 263-272 antibody positive group was 69.7%, significant higher than that of the negative group (42.1%, P < 0.05). In all patients, the stimulation index (SI) of T cell proliferation to CII263-272 peptide was positively correlated with the level of antibody (r = 0.68, P < 0.01). HLA-DR4 allele was detected in 16 out of the 40 patients. Positive T cell response and presence of antibody to CII 263-272 were not associated with HLA-DR4 phenotype. CONCLUSION: The formation of CII antibody may be related to B cell activation mediated by CII specific T cell.

Adolescent↗

[Diagnostic role of SOX13 antibody in latent autoimmune diabetes of adults].

OBJECTIVE: To explore the diagnostic role of SOX13 antibody in latent autoimmune diabetes of adults (LADA). METHODS: Sera of 328 patients with slow-onset diabetes and 120 sex and age-matched healthy controls underwent radiochemical test to detect the positive rates of SOX13-Ab, glutamic acid decarboxylace antibody (GAD-Ab) and carboxypeptidase H antibody (CPH-Ab). According to the GAD-Ab and CPH-Ab status the patients were divided into autoimmune (GAD-Ab and/or CPH-Ab positive, n = 130) and non-autoimmune (GAD-Ab and CPH-Ab negative, n = 198) diabetic subgroups. Then according to SOX13-Ab, GAD-Ab and CPH-Ab status, the diabetic patients were divided into 4 groups: SOX13-Ab positive, GAD-Ab positive, CPH-Ab positive, and antibody-negative group to compare their clinical characteristics. The effect of SOX13-Ab on islet beta-cell function was evaluated by comparison of C-peptide among the four subgroups. RESULTS: The positive rates of SOX13-Ab in the slow-onset diabetic patients (10.4%), autoimmune subgroup patients (13.1%), and non-autoimmune subgroup patients (8.6%) were all higher than that in the healthy controls (2.5%, all P < 0.05). Thirteen patients were positive for both SOX13-Ab and CPH-Ab (13/328, 4.0%), but only 2 were positive for both SOX13-Ab and GAD-Ab (2/328, 0.6%). The highest prevalence of SOX13-Ab was observed in the patients with the duration of disease ranging from 16 to 20 years. There were no differences in the clinical parameters between the SOX13-Ab positive and antibody-negative diabetic patients. CONCLUSION: SOX13-Ab testing helps improve the sensitivity of screening for LADA. SOX13-Ab positive patients tend to have a longer course of disease and varied clinical manifestations.

Adolescent↗

Dimeric hexakis(4-methylbenzoato)bis(1,10-phenanthroline)didysprosium(III).

The title compound, [Dy2(C8H7O2)6(C12H8N2)2], forms binuclear complexes, viz. di-mu-4-methylbenzoato-kappa4O:O'-bis[bis(4-methylbenzoato-kappa2O,O')(1,10-phenanthroline-kappa2N,N')dysprosium(III)] tetra-mu-4-methylbenzoato-kappa8O:O'-bis[(4-methylbenzoato-kappa2O,O')(1,10-phenanthroline-kappa2N,N')dysprosium(III)]. There are two independent binuclear complexes in the asymmetric unit, both of which are centrosymmetric. In one, the Dy(III) ions are linked by two bridging 4-methylbenzoate groups, while in the other, the Dy(III) ions are linked by four bridging 4-methylbenzoate groups. The remaining 4-methylbenzoate groups and 1,10-phenanthroline units coordinate to just one metal ion in bidentate modes.

Journal Article↗

A robust hybrid between genetic algorithm and support vector machine for extracting an optimal feature gene subset.

Development of a robust and efficient approach for extracting useful information from microarray data continues to be a significant and challenging task. Microarray data are characterized by a high dimension, high signal-to-noise ratio, and high correlations between genes, but with a relatively small sample size. Current methods for dimensional reduction can further be improved for the scenario of the presence of a single (or a few) high influential gene(s) in which its effect in the feature subset would prohibit inclusion of other important genes. We have formalized a robust gene selection approach based on a hybrid between genetic algorithm and support vector machine. The major goal of this hybridization was to exploit fully their respective merits (e.g., robustness to the size of solution space and capability of handling a very large dimension of feature genes) for identification of key feature genes (or molecular signatures) for a complex biological phenotype. We have applied the approach to the microarray data of diffuse large B cell lymphoma to demonstrate its behaviors and properties for mining the high-dimension data of genome-wide gene expression profiles. The resulting classifier(s) (the optimal gene subset(s)) has achieved the highest accuracy (99%) for prediction of independent microarray samples in comparisons with marginal filters and a hybrid between genetic algorithm and K nearest neighbors.

Algorithms↗

Disruption of the cellulose synthase gene, AtCesA8/IRX1, enhances drought and osmotic stress tolerance in Arabidopsis.

Two allelic Arabidopsis mutants, leaf wilting 2-1 and leaf wilting 2-2 (lew2-1 and lew2-2 ), were isolated in a screen for plants with altered drought stress responses. The mutants were more tolerant to drought stress as well as to NaCl, mannitol and other osmotic stresses. lew2 mutant plants accumulated more abscisic acid (ABA), proline and soluble sugars than the wild type. The expression of a stress-inducible marker gene RD29A, a proline synthesis-related gene P5CS (pyrroline-5-carboxylate synthase) and an ABA synthesis-related gene SDR1 (alcohol dehydrogenase/reductase) was higher in lew2 than in the wild type. Map-based cloning revealed that the lew2 mutants are new alleles of the AtCesA8/IRX1 gene which encodes a subunit of a cellulose synthesis complex. Our results suggest that cellulose synthesis is important for drought and osmotic stress responses including drought induction of gene expression.

Abscisic Acid↗

Irinotecan pharmacokinetic and pharmacogenomic alterations induced by methylselenocysteine in human head and neck xenograft tumors.

The combination of methylselenocysteine and irinotecan (CPT-11) is synergistic against FaDu and A253 xenografts. Methylselenocysteine/CPT-11 increased tumor cure rate to 100% in FaDu and to 60% in A253. In this study, the effect of methylselenocysteine on pharmacokinetic and pharmacogenetic profiles of genes relevant to CPT-11 metabolic pathway was evaluated to identify possible mechanisms associated with the observed combinational synergy. Nude mice bearing tumors (FaDu and A253) were treated with methylselenocysteine, CPT-11, and a combination of methylselenocysteine/CPT-11. Samples were collected and analyzed for plasma and intratumor concentration of CPT-11 and 7-ethyl-10-hydroxyl-camptothecin (SN-38) by high-performance liquid chromatography. The intratumor relative expression of genes related to the CPT-11 metabolic pathway was measured by real-time PCR. After methylselenocysteine treatment, the intratumor area under the concentration-time curve of SN-38 increased to a significantly higher level in A253 than in FaDu and was associated with increased expression of CES1 in both tumors. Methylselenocysteine/CPT-11 treatment, compared with CPT-11 alone, resulted in a significant decrease in levels of ABCC1 and DRG1 in FaDu tumors and an increase in levels of CYP3A5 and TNFSF6 in A253 tumors. No statistically significant changes induced by methylselenocysteine/CPT-11 were observed in the levels of other investigated variables. In conclusion, the significant increase in the cure rate after methylselenocysteine/CPT-11 could be related to increased drug delivery into both tumors (CES1), reduced resistance to SN-38 (ABCC1 and DRG1) in FaDu, and induced Fas ligand apoptosis (TNFSF6) in A253. No correlation was observed between cure rate and other investigated variables (transporters, degradation enzymes, DNA repair, and cell survival/death genes) in either tumor.

Animals↗

[Effect of Endotoxin on the expression of peroxisome proliferator-activated receptor alpha in the development of nonalcoholic steatohepatitis in rats].

OBJECTIVE: To study the effect of endotoxin on the expression of peroxisome proliferator-activated receptor alpha (PPARa) in the development of nonalcoholic steatohepatitis in rats. METHODS: A model of nonalcoholic steatohepatitis (NASH) was developed with Wistar rats fed a chow containing 20% maize oil for 14 weeks. The endotoxin group rats were intraperitoneally injected with lipopolysaccharide (LPS, 1 g/L, 3.0 ml/kg) once 4 hours before the end of the experiment. The concentrations of lipids, endotoxin, tumor necrosis factor-a, malondialdehyde, free fatty acid in plasma and hepatic tissues were determined and the degree of hepatocytic steatosis was studied. The expression of PPARa mRNA in hepatic tissues was measured using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The expression of PPARa mRNA in the hepatic tissue of the LPS group was downregulated markedly in comparison to that of the control group. The level of free fatty acid and endotoxin by secreting tumor necrosis factor-a increased and triglyceride accumulated in the liver caused malondialdehyde content to increase, then lipid peroxidation process enhanced and ALT activity increased. Thus, hepatic injury and inflammatory reaction could be accelerated. CONCLUSION: Endotoxemia can enhance hepatocellular steatosis and lead to NASH due to its downregulating the expression of PPARa mRNA.

Animals↗

[Construction of cblN/Zap and its down-regulating effect on TCRzeta protein in Jurkat cells].

AIM: To construct the chimeric cblN/Zap molecule, and to observe its effect on TCRzeta protein in pcDNA3.1(+)-cblN/Zab transfected Jurkat cells. METHODS: Total RNA of Jurkat cells were isolated and reversely transcribed into cDNA, which were used as templates to amplify Zap SH2 by PCR. cblN gene tagged with 24 bp flag was amplified by PCR using pEFHAcbl plasmid encoding human cbl as templates. BamH I and EcoR V restriction enzyme digestion sites were introduced into flank SH2 in pcDNA3.1(+) cblN by overlapping extension PCR. Then pcDNA3.1(+)-cblN/Zap was obtained by replacing SH2 of cblN with ZapSH2. After confirmation by enzyme digestion and sequencing, the recombined vector was stably transfected into Jurkat cells with lipofectin. The expression of flag-cblN/Zap was detected by RT-PCR and Western blot, and its effect on TCRzeta protein was analyzed by Western blot. RESULTS: Restriction enzyme digestion analysis of the pcDNA3.1(+)-cblN/Zap recombinant vector showed that the expected fragments were produced and confirmed by sequencing. pcDNA3.1(+)-cblN/Zap was stably transfected into Jurkat cells and the expression of flag-cblN/Zap in the stable clones was confirmed by both RT-PCR and Western blot. The expressed cblN/Zap down-regulated TCRzeta protein in Jurkat cells. CONCLUSION: Chimeric cblN/Zap is able to down-regulate TCRzeta in Jurkat cells.

Animals↗

[Microvessel density and expressions of survivin and vascular endothelial growth factor in non-small cell lung cancer and their correlations to clinicopathologic features].

BACKGROUND & OBJECTIVE: Survivin, an anti-apoptosis gene, expresses in most tumors, and takes part in tumor angiogenesis. This study was to investigate microvessel density (MVD) and expressions of Survivin and vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC), and explore their correlations to clinicopathologic features of NSCLC. METHODS: MVD and expressions of Survivin and VEGF in 96 specimens of NSCLC tissues, 31 specimens of tumor adjacent tissues, and 20 specimens of benign lesions were detected by SP immunohistochemistry; their interrelations and correlations to clinicopathologic features of NSCLC were analyzed. RESULTS: Positive rate of Survivin was significantly higher in NSCLC than in adjacent tissues and benign lesions (69.8% vs. 16.1% and 0, P<0.05); its expression was related with differentiation and TNM stage of NSCLC. Positive rate of VEGF was significantly higher in NSCLC than in adjacent tissues and benign lesions (72.9% vs. 45.2% and 25.0%, P<0.05); its expression was related with lymph node metastasis and TNM stage of NSCLC. MVD was significantly higher in NSCLC than in adjacent tissues and benign lesions (24.44+/-7.79 vs. 19.37+/-5.26 and 11.83+/-6.25, P<0.05), and was related with lymph node metastasis and TNM stage of NSCLC. Survivin expression was positively correlated with VEGF expression and MVD. CONCLUSION: Survivin is overexpressed in NSCLC, which relates with differentiation and TNM stage of NSCLC and takes part in angiogenesis.

Adult↗

[Research on pattern classification methods using gene expression data].

One of the applications of cDNA microarrays is to recognize the class and subclass of diseases such as cancers on the basis of statistical pattern classification methods using gene expression data. In this paper, we apply 2000 genes expression dataset provided by Affymatrix Company: 40 samples of intestine cancer tissue and 22 samples of normal tissue. We compare the performance of four pattern classification methods based on different feature selection methods. These pattern classification methods include: Fisher linear discriminate, Logit nonlinear discriminate, the least distance and K-nearest neighbor classifier. The results show firstly that four pattern classifiers based on the feature selection methods of t-test and classification tree all have better performance than those based on the stochastic feature selection methods, secondly that K-nearest neighbor classifier has the best performance, thirdly that both the least distance classifier and K-nearest neighbor classifier have better generalization, fourthly that four classifiers are less sensitive to the composition of samples.

Gene Expression↗

[Experimental testing of micro biochemical analytical system].

A micro biochemical analytical system based on a micro fiber spectrometer is introduced. Experiment was carried out to calibrate and test the analysis system. In the experiment, the absorption spectra of Fe2+ -ferroin solution bodies with different concentrations were obtained. The working curve shows a fine linearity of the analysis system. The authors also compared the experimental results obtained from 722-spectrometer and those from our analysis system. It was shown that their system can meet the requirement of practical use. This system also has many advantages, such as real-time whole spectrum analyzing and small volume, and is an ideal instrument for biochemical analysis.

Chemistry Techniques, Analytical↗