OBJECTIVETo investigate synergistically killing effect of histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) combined with imatinib on human chronic myeloid leukemia (CML) cell line.

METHODSK562 cells were co-treated with SAHA and imatinib. Cell growth was measured by MTT assay. Apoptosis was determined using Hoechst staining apoptosis detection kit and flow cytometric analysis. Activation of Caspase pathway, expression of Bcr-Abl and its downstream target genes, and expression of anti-apoptotic proteins were detected by Western blot.

RESULTSSAHA synergized the cytotoxicity of imatinib against leukemia K562 cells, concomitantly with increased apoptosis and enhanced activation of Caspase-3, -8 and PRAP. The combination therapy resulted in significantly lower levels of Bcr-Abl,phosphorylated Bcr-Abl compared to treatment with either SAHA or imatinib alone. Furthermore,the co-treatment resulted in down-regulation of anti-apoptotic protein Mcl-1 expression. Also,marked down-regulated expression of JAK2,STAT5,and phosphorylated STAT5 was detected in the combination therapy.

CONCLUSIONCombining HDAC inhibitor SAHA with imatinib can kill CML cells synergistically by inhibiting cell growth and inducing apoptosis, which is associated with activation of Caspase pathway and regulation of anti-apoptotic proteins.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Benzamides ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Drug Synergism ; Fusion Proteins, bcr-abl ; metabolism ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Hydroxamic Acids ; pharmacology ; Imatinib Mesylate ; Intracellular Signaling Peptides and Proteins ; metabolism ; Janus Kinase 2 ; metabolism ; K562 Cells ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology ; STAT5 Transcription Factor ; metabolism

Objective To observe whether the expression of interferon-regulatory factor genes are re- lated to systemic lupus erythematosus (SLE).Methods The clinical data of 45 SLE patients and 37 normal controls were collected.Total RNA of peripheral blood was extracted and transcripted into cDNA.Sybr green dye based real-time quantitative PCR method was used to compare the expression (indicated as-??Ct value) of IRFI,IRF4,IRF8 in patients with SLE and those in the controls.Results The levels of IRF1,IRF4 and IRF8 mRNA were-3.90?0.19,-8.04?0.25 and 3.60?0.15 respectively in normal controls.In SLE patients, IRF4 mRNA expression was -8.82?0.18,higher than that in normal (P=0.011).But IRF8 mRNA expression was 3.09?0.13,lower than that in normal (P=0.012).Conclusion Abnormal IRF mRNA expression is found in the peripheral blood of SLE patients.IRFs may play roles in the pathogenesis of SLE by affecting the differen- tiation of Th cells.

OBJECTIVETo investigate the distribution characteristics of the single nucleotide polymorphisms (SNPs) in the promoter region of the toll-like receptor 9 gene (TLR9) in Chinese Han children from Zhejiang province, and their associations with asthma susceptibility and phenotypes.

METHODSA case-control study was conducted. A total of 312 asthmatic children aged between 1.9 and 11.6 and 339 age matched healthy controls were enrolled in this study from April 2007 to November 2008. The -1486 C/T in rs187084 and -1237 C/T in rs5743836 loci of the TLR9 gene were genotyped by direct DNA sequencing of the PCR products. Serum levels of IFN gamma, IL-12 and IL-4 were detected by enzyme linked immunosorbent assay.Serum levels of total IgE were detected by chemiluminescence, and serum levels of antigen specific IgE antibodies were detected by fluoroenzymeimmunoassay.

RESULTS(1) The -1486 C/T polymorphism was identified in both groups. The genotype frequencies of TT, TC and CC at -1486 C/T were 41.0%, 44.3%, 14.7% in the healthy controls, and 38.8%, 48.4%, 12.8% in the asthmatic children. The -1237 C/T polymorphism was not detected in the population. (2) There were no statistically significant differences in the allele and genotype frequencies at the -1486 C/T locus between the two groups (P;>0.05). (3) Serum levels of IFN gamma and IL-4 differed significantly among the three genotypes at the -1486 C/T locus in asthmatic children (P<0.01). The CC genotype had the lowest levels of serum IFN gamma and the highest levels of serum IL-4 among the three genotypes. There were no significant differences in these cytokines among the healthy controls (P>0.05). No statistical differences of serum IL-12 were found among the three genotypes in the two groups (P>0.05). (4) There were no significant differences of total IgE (log-transformed) among the three genotypes in the asthmatic children (P>0.05).

CONCLUSIONThe -1237 C/T polymorphism of TLR9 gene was not detected in Chinese Han children in this study. The -1486 C/T polymorphism was associated with the levels of serum IFN gamma and IL-4 in children with asthma. However, there were no correlations between the -1486C/T polymorphism and serum IL-12 levels, total IgE levels or asthmatic susceptibility.

Asthma ; blood ; genetics ; Case-Control Studies ; Child ; China ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Toll-Like Receptor 9 ; genetics

Objective To evaluate the solute clearance characteristics of REXEEDTM series dialyzers during high-flux dialysis, and explore the care characteristics. Methods A randomized crossover study of 3×3 Latin square was designed based on different dialyzers. Eighteen patients with regular hemodialysis underwent dialysis with REXEEDTM-15AC dialyzer, REXEEDTM-15UC dialyzer and controlled APS-15U dialyzer, respectively. Blood samples were obtained from the blood flow entrance and exit of dialyzers, levels of urea nitrogen, creatinine, phosphate and β2-microglobulin were detected, and solute clearance rates were calculated. Before and after the third dialysis with each dialyzer, blood samples were obtained to measure the levels of urea nitrogen and creatinine, and the rates of decrease were calculated. The vital signs of each patient were intensively observed, and the venous pressure and transmembrane pressure were monitored from the dialyzers. Results The urea nitrogen clearance rates of REXEEDTM-15AC dialyzer and REXEEDTM-15UC dialyzer were significantly higher than that of APS-15U dialyzer (P<0.05). The creatinine clearance rate of REXEEDTM-15AC dialyzer was significantly higher than that of APS-15U dialyzer(P<0.05). There was no significant difference in the rate of decrease in blood urea nitrogen among different dialyzers of the same patient(>65 % for all patients). The vital signs were stable with no adverse events during dialysis, and there was no abnormal findings in laboratory security parameters. Conclusion REXEEDTM series dialyzers are effective and safe for clinical application. Great importance should be attached to the complaints from patients during dialysis. For those with less ultrafiltration, fluid as well as uhrafiltration should be supplemented to increase the transmembrane pressure.

AIMTo observe the effect of phenolic alkaloids of Menispermum dauricum (PAMD) on the hemodynamics, coronary circulation and oxygen metabolism of the myocardium in anesthetized dogs.

METHODSIn this study, the changes of LVSP, LVEDP and +/- dp/dtmax, the flow of coronary artery and myocardial energy metabolism were measured in anesthetized dog with PAMD or NS.

RESULTSIn the anesthetized dogs, compared with pre-treatment status, PAMD at 3.5 and 7.0 mg.kg-1 caused decreases in the left ventricular systolic pressure(LVSP), +/- dp/dtmax, heart rate, the rate of oxygen utilization, the coronary and general peripheral resistance. It was found to increase myocardial oxygen and coronary flow. There were no significant change in the left ventricular end diastolic pressure (LVEDP).

CONCLUSIONPAMD can ameliorate hemodynamics, coronary circulation and myocardial metabolism.

Alkaloids ; isolation & purification ; pharmacology ; Animals ; Blood Pressure ; drug effects ; Cardiac Output ; drug effects ; Coronary Circulation ; drug effects ; Dogs ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Heart Rate ; drug effects ; Male ; Menispermum ; chemistry ; Oxygen Consumption ; drug effects ; Plants, Medicinal ; chemistry ; Random Allocation ; Vascular Resistance ; drug effects

OBJECTIVETo study the central pharmacological effect of the water and chloroform-extract compounds from C. chinese in mice.

METHODThe independent activity test and the hypnotic synergism test by sub-threshold hypnotic dosage of pentobarbital were employed to evaluate the central pharmacological effect of the extract-compounds, and the minimal neurotoxicity was evaluated by the rotorod test.

RESULTthe extract-compounds exhibited significant dose-related inhibition effect of the spontaneous motor activity in mice after intraperitoneal administration. And the two extract-compounds promoted the hypnotic effect by sub-threshold hypnotic dosage administration of pentobarbital, and produced ED50 value of 2.36 g kg (-1) and 0.75 g kg(-1), respectively. Also, both extract-compounds showed no neurotoxicity in the experiment.

CONCLUSIONThe extract compounds from C. chinese showed inhibitional effect on CNS.

Animals ; Central Nervous System ; drug effects ; physiology ; Chloroform ; Cynanchum ; chemistry ; Dose-Response Relationship, Drug ; Drug Synergism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; toxicity ; Female ; Hypnotics and Sedatives ; isolation & purification ; pharmacology ; Male ; Mice ; Mice, Inbred ICR ; Motor Activity ; drug effects ; Pentobarbital ; pharmacology ; Plants, Medicinal ; chemistry ; Random Allocation ; Sleep ; drug effects ; Water

OBJECTIVETo investigate the expressions of telomerase reverse transcriptase (TRT) and vascular endothelial growth factor (VEGF) and their correlation in prostate cancer (PCa).

METHODSTRT and VEGF expressions were assayed in 30 cases of PCa and 30 cases of benign prostatic hyperplasia (BPH) by means of immunohistochemistry (SP) combined with computer assisted image analysis.

RESULTSThe expression of TRT was detected in 19 of the 30 cases of PCa and 5 of 30 cases of BPH, and that of VEGF in 23 of the 30 PCa and 14 of the 30 BPH patients. TRT and VEGF expressions were significantly higher in cancer tissues than in BPH (P < 0.05). A significant correlation was observed between TRT and VEGF expressions (r = 0.8333, P < 0.05).

CONCLUSIONThe expression of TRT or VEGF might be a malignant phenotype in PCa. The expression of TRT is significantly correlated with that of VEGF, but the mechanisms are yet to be further studied.

Animals ; Humans ; Immunohistochemistry ; Male ; Prostatic Hyperplasia ; metabolism ; pathology ; Prostatic Neoplasms ; metabolism ; pathology ; Rabbits ; Telomerase ; biosynthesis ; Vascular Endothelial Growth Factor A ; biosynthesis

Objective To study the effect ofmethylprednisolone (MP) on the expression of heatshock protein 70 (HSP70) following the injury of spinal cord (SC1) in rats. Methods 125 SD rots wererandomly divided into 5 groups: the simple operation group (n=30), the MP control group (n=30), theinjury group (n=30), the MP treatment group (n=30) and the normal control group (n=5). Specimen of thespinal cord were collected at 2, 6, 12, 24, 48, 72 h after SCI, respectively. Their pathomorphology wasobserved and HSP70 expression was detected by immunohistochemistry. Results After treatment ofMP, the secondary injury was lightened, according to the HE staining of the specimen.lmmunohistochemistry revealed that there were no HSP70 expression in the normal control group and theMP control group, that there was a little HSP70 in the simple operation group, and that there was a lot ofHSP70 in the injury group 2 h after injury, and the expression peaked at 24 h and maintained to 72 h afterinjury. The expression was significantly increased and the peak of expression was in advance in the MPtreatment group as compared with injury group, and it was also found in neuropil of white substance ofspinal cord. Conclusion High-dose NIP can obviously increase the expression of HSP70 in injuredspinal cord, and has the peak time of expression in advance, and enlarge the scope of expression. It maybe one of the mechanism to protect the spinal cord that MP guide myeloid tissue to overexpress HSP70after spinal cord injury.

[Objective]To investigate the characteristics of immunophenotypes in hepatocellular carcinoma(HCC) before liver transplantation.[Methods]The immunophenotypes of T-,B- cells,monocytes,dendritic cells(DC)and NK-cells in peripheral blood from 6 HCC patient who were ready to have liver transplantation and 6 healthy volunteers were analyzed by multicolor flow cytometry.[Results]In the patients,the proportions of CD4+PD-1+T cells,Treg cell (CD4+CD25+CD39+T cells),CD19+B cells,Plasmablasts(CD27highCD38highIgD-IgM-),classical monocytes(CD14high CD16-)and mature NK-cells(CD3-CD56high)were all higher than those in the healthy controls(all P<0.05).However, marginal zone B cell(CD27+IgD+),Non-switched B cells(CD27+CD38dimIgM+),intermediate monocytes(CD14high CD16+)and immature NK-cells(CD3-CD56+)were lower than those in the healthy controls(all P<0.05). And there wasn't any obvious difference in quantity being observed among other cell types.[Conclusion]There was difference in the immunophenotypes of immune cells in peripheral blood between HCC patients before liver transplantation and healthy people.And this finding exerts important effects on monitoring the immune status of the patients after liver transplantation and guiding the administrations of immunosuppressors.

OBJECTIVEBased on the 2002 WHO health survey data, to explore the latent relationship among self-reported health level, the actual level of health, the social demographic characteristics and the risk factors, and to analyze the influence of the various surveillance indicators on self-reported health and the degree that the self-reported health explained the actual level of health.

METHODSField tests for various components of the World health survey were conducted in nine countries during 2002, including India, Brazil, Burkina, Hungary, Nepal, Russia, Spain, Tunisia, and Vietnam (29 971). The survey questionnaire included a self-assessment component and anchoring vignette component. The self-assessment component data was adjusted and eliminated the affect of "cut-point bias" by using the anchoring vignette component data, and then was used to build the structural equation model on the relationship among self-reported health level, actual health level, social demographic characteristics and the risk factors.

RESULTSIn the final structural equation model, "the actual level of health" = 0.80 × "the self-reported health level" + (-0.04) × "the social demographic characteristics" + (-0.08) × "the risk factors" (R(2) = 0.66), and "the self-reported health level" = (-0.70) × "the social demographic characteristics" + 0.10 × "the risk factors" (R(2) = 0.55). The standardized total effect of self-reported health to the actual level of health was 0.80, and that of the social demographic characteristics to the self-reported health and the actual level of health were -0.70 and -0.60, respectively. And the 16 items of self-reported health consisted of 8 dimensions; and sorted by the power of impact to the actual health level, they were mobility, pain and discomfort, sleep, cognition, feelings, self-care ability, visual capacity and interpersonal activities.

CONCLUSIONThere were significant linear correlation relationship between the actual level of health and the self-reported health, as well as between the self-reported health and the social demographic characteristics. And the self-reported 16 items used by the 2002 WHO health survey played an important role in the health evaluation of population.

Demography ; Health Status ; Health Surveys ; Humans ; Models, Statistical ; Risk Factors ; Self Report ; Surveys and Questionnaires ; World Health Organization