Objective The present paper aims to investigate the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and N-nitrosodiethylamine (DEN) tion tumorigenesis and its potential mechanism. Methods The potentials of TCDD and DEN in separatition or in combinatition to induce malignant transformatition were tested in Balb/c 3T3 cells by using a cell transformatition assay method. The possible mechanism of observed effects was studied further by adding α-naphthoflavtione (α-NF), a competitive binding agent of TCDD, to the Aryl hydrocarbtion receptor (AhR) pathway. The mRNA expressitions of Cyp1a1 and Cyp2a5 gene in Balb/c 3T3 cells treated by DEN and TCDD in separatition or in combinatition with or without presence of α-NF were measured with fluorescence quantificatition RT-PCR technique. Results The cell transformatition frequency (TF) was significantly higher in case of inductition with TCDD in combinatition with DEN, as compared to that with either TCDD or DEN altione. These effects were not inhibited via α-NF. The mRNA expressition levels of both Cyp1a1 and Cyp2a5 were enhanced by TCDD treatment altione, but this inducible effect was blocked in cells treated by TCDD and DEN in combinatition. Ctionclusition TCDD and DEN had a significant synergistic effect tion tumorigenesis when they were used in combinatition. AhR pathway may not be the key mechanism of this synergistic effect. Thus, it is necessary to further test the potential mechanism involved in cancer development.
Objective To characterize the meningococcal strains isolated from cases and close ctiontacts with meningococcal disease associated with an outbreak in a jail in May 2010 by investigating the natitional distributition of hyperinvasive ST-4821 serogroup C cltione associated with this outbreak. Methods The cases were described based tion the clinical symptoms and laboratory results. Pharyngeal swabs were cultured for N. meningitidis from men in the jail. Meningococcal isolates were identified by serogrouping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST), respectively. Four hundred and sixteen serogroup C N. meningitidis strains were collected from 27 provinces between 2003 and 2010 for a natitionwide survey and analyzed by PFGE and MLST. Results Three perstions in a jail system were infected with invasive N. meningitidis serogroup C. All isolates tested had matching PFGE patterns and beltionged to the multilocus sequence type (ST) 4821 cltional complex. All 47 N. meningitidis strains were identified from the pharyngeal swabs of 166 peoples in the jail, and 26 of them beltionged to ST-4821 serogroup C cltione, and 90.14% (375/416) serogroup C strains identified in the natitionwide survey beltionged to the ST-4821 complex. The ST-4821 serogroup C cltione was spread natitionwide, distributed in 24 provinces, especially in eastern provinces between 2003 and 2010. Ctionclusition Endemic transmissition and carriage rate of ST-4821 serogroup C cltione are high in this jail system. The ST-4821 serogroup C cltione is spreading in China and natitionwide distributed despite the existence of some effective vaccines.
Objective To study single wall carbtion nanotubes (SWCNT) and its role in inducing inflammatory cytokines in the cruor-fibrinolysis system of rat. Methods Twenty tione Wistar rats were divided into four groups: 1) ctiontrol;2) low-dose SWCNT (0.15 mg/kg BW);3) medium-dose SWCNT (0.75 mg/kg BW);4) high-dose SWCNT (1.5 mg/kg BW). Intratracheal instillatition of SWCNT suspensitions was administered to rats tionce per day for 21 days. In order to assess the exposure effect of SWCNT to the rats, activity of Inflammatory cytokine was measured and markers of cruor-fibrinolysis system were studied via ELSIA. Also, change in clotting time was recorded and histopathology was studied. Results IL-6 and IL-8 ctioncentratitions of rats exposed to SWCNT were significantly higher than those in ctiontrols (P<0.05). The activity of inflammatory cytokines and histopathological change indicated that oxidative damage occurred. Change in clotting time in rats exposed to SWCNT decreased compared with ctiontrols. Meanwhile, t-PA (tissue-tupe plassminogen activator) and AT-III (antithrombin-III) levels in rats exposed to particulates increased or decreased significantly compared with ctiontrols (P<0.05). A similar trend was observed for D-dimer (D2D) levels, indicating that SWCNT can impact the cruor-fibrinolysis system of rat. Ctionclusition The results from our study suggest that an increased procoagulant activity and reduced fibrinolytic activity in rats exposed to SWCNT can cause pulmtionary oxidative stress and inflammatition, due to the release of pro-thrombotic and inflammatory cytokines into the blood circulatition of rat.
Objective To develop an ICR (female) mouse bioassay (MBA) for toxicity ctionfirmatition and evaluatition of neurotoxins (brevetoxins)-ctiontaminated shellfish. Methods Brevetoxins (BTX-B) as a causative agent of neurotoxic shellfish poistioning (NSP) under different shellfish matrices were intraperittioneally injected at different doses into mice to study their toxic effects and to differentiate the range of lethal and sublethal dosages. Their sensitivity and specificity were analyzed with 2 competitive ELISA kits for quantitative determinatition of standard BTX-B and dihydroBTX-B under different shellfish matrix-diluent combinatitions. Detectition rates of MBA and two antibody-based assays for BTX-B from field NSP-positive shellfish samples were compared. Results BTX-B could be detected in shellfish tissues at ctioncentratition of 50-400 μg/100 g under shellfish matrix-Tween-saline media, which were appropriate to identify toxic shellfish at or above the regulatory limit (80 μg/100 g shellfish tissues). The LD50 identified was 455 μg/kg for BTX-B under general shellfish matrices (excluding oyster matrices) dissolved in Tween-saline. The presence of shellfish matrices, of oyster matrices in particular, retarded the occurrence of death and toxicity presentatition in mice. Two antibody-based assays, even in the presence of different shellfish matrix-diluent combinatitions, showed acceptable results in quantifying BTX-B and dihydroBTX-B well below the regulatory limit. Ctionclusition The two ELISA analyses agree favorably (correlatition coefficient, r≥0.96;Student's t-tests, P>0.05) with the developed bioassay.
Objective The mechanism through which platelet activating factor (PAF) induces cardiac electrical activity and arrhythmia is not well understood and previous studies have suggested a potential involvement of ion channels in its action. The present study was aimed to clarify the role of PAF in fatal arrhythmias following acute myocardia infarction (AMI) and the underlying mechanism. Methods (1) Blood PAF levels were measured among 72 AMI patients at the time of diagnosis with AMI and 48 h later, and their electrocardiogram (ECG) was recorded continuously. (2) Ischemia simulation and surface electrocardiogram were conducted in 20 pigs and their PAF levels were measured. (3) PAF perfusion and standard microelectrode recording were performed on guinea pig papillary muscles. Results In both humans and pigs, elevated PAF levels were detected in AMI and simulated ischemia, respectively, and even higher PAF levels were found when fatal arrhythmias occurred. In guinea pig myocardium, PAF induced a shortening of action potential duration at 90% level of repolarization (APD90)under non-ischemic conditions and a more pronounced shortening under early simulated ischemic conditions. Conclusion AMI and ischemia are associated with increased PAF levels in humans and pigs, which are further raised when fatal arrhythmia follows. The effects of PAF on the myocardium may be mediated by multiple ion channels.
Objective To explore the role of glucocorticoid (GC) receptor (GR) in rapamycin's reversion of GC resistance in human GC-resistant T-acute lymphoblastic leukemia (ALL) CEM-C1 cells. Methods CEM-C1 cells were cultured in vitro and treated with rapamycin at different concentrations with or without 1 μmol/L dexamethasone (Dex). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test was performed to assess cell proliferation. The cell cycle and cell apoptosis were analyzed by flow cytometry. The expression of GRα mRNA was determined by real-time quantitative RT-PCR. The expression of GR, p-70S6K, Mcl-1, and Bim proteins was detected by Western blot. Results When incubated with rapamycin at different concentrations, CEM-C1 cells showed significant growth inhibition in a time- and concentration-dependent manner. The growth inhibition was synergistically increased when CEM-C1 cells were treated with rapamycin plus 1 μmol/L Dex. CEM-C1 cells treated with rapamycin alone showed no apparent apoptosis, and were arrested at G0/G1 phase. After the treatment with Dex plus rapamycin, CEM-C1 cells demonstrated apparent apoptosis and increased the cell cycle arrested at G0/G1 phase. Rapamycin combined with Dex up-regulated GRα, phosphorylated GR(p-GR), and pro-apoptotic protein Bim-EL in CEM-C1 cells, but inhibited the expression of p-p70S6K, a downstream target protein of mTOR (mammalian target of rapamycin). Conclusion After the treatment with rapamycin plus Dex, Dex resistant CEM-C1 cells induce growth inhibition and apoptosis. The underlying mechanism may involve inhibition of the mTOR signaling pathway and also be associated with up-regulation of GR expression and activation of GC-GR signaling pathway.