Search

Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are characteristic of AML. Zinc finger protein 382 (ZNF382) has been suggested to be a tumor suppressor gene possibly regulated by promoter hypermethylation in various types of human cancer. However, ZNF382 expression and methylation status in pediatric AML is unknown. In the present study, ZNF382 transcription levels were evaluated by quantitative reverse-transcription PCR. Methylation status was investigated by methylation-specific (MSP) PCR and bisulfate genomic sequencing (BGS). The prognostic significance of ZNF382 expression and promoter methylation was assessed in 105 cases of pediatric AML. The array data suggested that the ZNF382 promoter was hypermethylated in the AML cases examined. MSP PCR and BGS analysis revealed that ZNF382 was hypermethylated in leukemia cell lines. Furthermore, treatment with 5-aza-2'-deoxycytidine (5-Aza) upregulated ZNF382 expression in the selected leukemia cell lines. The aberrant methylation of ZNF382 was observed in 10% (2/20) of the control samples compared with 26.7% (28/105) of the AML samples. ZNF382 expression was significantly decreased in the 105 AML patients compared with the controls. Patients with ZNF382 methylation showed lower ZNF382 transcript levels compared with patients exhibiting no methylation. There were no significant differences in clinical characteristics or cytogenetic analysis between the patients with or without ZNF382 methylation. ZNF382 methylation correlated with minimal residual disease (MRD). Kaplan-Meier survival analysis revealed similar survival times in the samples with ZNF382 methylation, and multivariate analysis revealed that ZNF382 methylation was not an independent prognostic factor in pediatric AML. The epigenetic inactivation of ZNF382 by promoter hypermethylation can be observed in AML cell lines and pediatric AML samples. Therefore, our study suggests that ZNF382 may be considered a putative tumor suppressor gene in pediatric AML. However, further studies focusing on the mechanisms responsible for ZNF382 downregulation in pediatric leukemia are required.

Background: Acute myeloid leukemia (AML) is the second most common form of leukemia in children. Aberrant DNA methylation patterns are a characteristic feature in various tumors, including AML. Metallothionein III (MT3) is a tumor suppresser reported to show promoter hypermethylated in various cancers. However, the expression and molecular function of MT3 in pediatric AML is unclear. Methods: Eleven human leukemia cell lines and 41 pediatric AML samples and 20 NBM/ITP (Norma bone marrow/ Idiopathic thrombocytopenic purpura) control samples were analyzed. Transcription levels of MT3 were evaluated by semi-quantitative and real-time PCR. MT3 methylation status was determined by methylation specific PCR (MSP) and bisulfite genomic sequencing (BSG). The molecular mechanism of MT3 was investigated by apoptosis assays and PCR array analysis. Results: The MT3 promoter was hypermethylated in leukemia cell lines. More CpG’s methylated of MT3 was observed 39.0% pediatric AML samples compared to 10.0% NBM controls. Transcription of MT3 was also significantly decreased in AML samples compared to NBM/ITP controls (P< 0.001); patients with methylated MT3 exhibited lower levels of MT3 expression compared to those with unmethylated MT3 (P = 0.049). After transfection with MT3 lentivirus, proliferation was significantly inhibited in AML cells in a dose-dependent manner (P< 0.05). Annexin V assay showed that apoptosis was significantly upregulated MT3-overexpressing AML cells compared to controls. Real-time PCR array analysis revealed 34 dysregulated genes that may be implicated in MT3 overexpression and apoptosis in AML, including FOXO1. Conclusion: MT3 may be a putative tumor suppressor gene in pediatric AML. Epigenetic inactivation of MT3 via promoter hypermethylation was observed in both AML cell lines and pediatric AML samples. Overexpression of MT3 may inhibit proliferation and induce apoptosis in AML cells. FOXO1 was dysregulated in MT3-overexpressing cells, offering an insight into the mechanism of MT3-induced apoptosis. However, further research is required to determine the underlying molecular details.

Snail, a potent repressor of E-cadherin expression, plays a key role in epithelial-to-mesenchymal transition (EMT) in epithelial cancer. Recently, EMT and stemness programs are found linked together. In the current study, the expression of Snail and its contribution to cancer stem cell (CSC) marker expression, invasiveness, self-renewal, clonogenicity, and tumorigenicity of pancreatic cancer cells were studied. Our results showed that Snail was highly expressed in CSC(high) cell line Panc-1. Stable, short hairpin RNA (shRNA)-mediated Snail knockdown decreased invasion in Panc-1 cells, in line with increased E-cadherin expression and its translocation from the nucleus to the membrane. Snail silencing in Panc-1 also inhibited CSC marker ALDH expression, together with decreased sphere and colony forming capacity, which was highly consistent with the expression of stem cell associated transcription factors like Sox2 and Oct4. In mouse xenograft models, knockdown of Snail led to a reduced number of tumor-bearing mice and a reduced average size of tumors, which had a stronger membrane staining of E-cadherin and lighter staining of Oct4. Collectively, these findings implicate Snail is required for the maintenance of stem cell-like phenotype in pancreatic cancer, and inhibition of Snail could be an efficient strategy to treat pancreatic cancer by targeting CSCs.

Purpose Cardiopulmonary bypass (CPB) during pediatric cardiac surgery often elicits a systemic inflammatory response followed by a compromised immune response, which has been attributed to the morbidity of postoperative infection; however, the underlying mechanism(s) has not yet been fully elucidated. We hypothesized that CPB inhibits the activation of Toll-like receptor (TLR) signal transduction pathways, thereby causing an immunosuppressive state after pediatric cardiac surgery. Methods We examined 20 children with congenital heart disease undergoing pediatric cardiac surgery. Results Cardiopulmonary bypass differentially affected lipopolysaccharide (LPS)- or bacterial lipoprotein (BLP)–stimulated ex vivo production of proinflammatory and anti-inflammatory cytokines, with significantly diminished tumor necrosis factor α , interleukin (IL) 1 β , IL-6, and IL-8, but substantially enhanced IL-10 production. Consistent with the reduced inflammatory response, CPB strongly inhibited LPS- or BLP-activated TLR signal transduction pathways in monocytes with down-regulated expression of CD14, TLR4, and TLR2 and with suppressed phosphorylation of nuclear factor κ B p65, p38, and extracellular signal-regulated kinase 1/2. Conclusions These results indicate that CPB during pediatric cardiac surgery causes substantially reduced production of inflammatory cytokines in response to bacterial component LPS or BLP stimulation, which is associated with CPB-induced suppression of TLR-mediated signal transduction pathways. This reduced inflammatory response after CPB in children with congenital heart disease may predispose them to an increased risk of postoperative infection.

B7-H3, a new member of the B7 superfamily, plays a key role in the regulation of T cell-mediated immune responses. Our previous work showed that B7-H3 strongly augmented both LPS- and bacterial lipoprotein-induced NF-κB activation and inflammatory response, and soluble B7-H3 was elevated in CSF and plasma of patients with bacterial meningitis. MMP-9 has been implicated in blood–brain barrier disruption, inflammation, and vasculitis during the pathogenesis of bacterial meningitis. In this study, we report that in a murine model of pneumococcal meningitis, B7-H3 treatment enhances inflammatory response in the meninges, upregulates MMP-9 expression in cerebral parenchyma, and deteriorates clinical disease status indicated by weight loss and impaired movement ability. In vitro results showed that B7-H3 augmented MMP-9 secretion from Streptococcus pneumoniae-stimulated microglia cells. Thus, our data indicate that B7-H3 contributes to the development of pneumococcal meningitis by exaggerating inflammatory responses and upregulating MMP-9 activity in CNS, which ultimately lead to neuronal injury.

For the optimal slip ratio, this paper adopted intelligent control technology to realize automobile Anti-lock control system. First, the two dimensional fuzzy Anti-lock Braking System(ABS) controller was designed, followed by design of the fuzzy neural network ABS controller. Finally the genetic algorithm was adopted to optimize the weights and thresholds of fuzzy neural network. Simulation results show a good anti-lock braking effect can be obtained by adopting the compound intelligent control technology.

In this paper, prediction model for ultimate vertical bearing capacity of cast-in-situ single pile has been designed on RBF neural network, and data has been trained and simulated by Matlab neural network tool box. It shows that the model is feasible and the prediction result is desirable.

As new media, ceramic-corrosion-cell fillers (Cathode Ceramic-corrosion-cell Fillers – CCF, and Anode Ceramic-corrosion-cell Fillers – ACF) employed in electrobath were investigated for cyclohexanone industry wastewater treatment. 60.0 wt% of dried sewage sludge and 40.0 wt% of clay, 40.0 wt% of scrap iron and 60.0 wt% of clay were utilized as raw materials for the preparation of raw CCF and ACF, respectively. The raw CCF and ACF were respectively sintered at 400 °C for 20 min in anoxic conditions. The physical properties (bulk density, grain density and water absorption), structural and morphological characters and toxic metal leaching contents were tested. The influences of pH, hydraulic retention time (HRT) and the media height on removal of COD Cr and cyclohexanone were studied. The results showed that the bulk density and grain density of CCF and ACF were 869.0 kg m −3 and 936.3 kg m −3 , 1245.0 kg m −3 and 1420.0 kg m −3 , respectively. The contents of toxic metal (Cu, Zn, Cd, Pb, Cr, Ba, Ni and As) were all below the detection limit. When pH of 3–4, HRT of 6 h and the media height of 60 cm were applied, about 90% of COD cr and cyclohexanone were removed.

Forecasting model of the rate of rock burst acoustic emission time series has been established by BP neural network, and it is combined with the catastrophe theory to determine whether the rock burst. And then the experimental data recorded are used for examining the model. The results show that the degree of prediction accuracy is high, and it proves that the prediction model of rock burst is feasible.

Several cell-based therapies for peripheral arterial disease (PAD) have been studied in multiple clinical trials; however, the outcome of this treatment remains controversial. The aim of this study was to perform a meta-analysis of the clinical trials on stem cell-based therapy after PAD. We searched for clinical trials that investigated the effect of stem cell-based therapy on patients with PAD and were published between January 2000 and October 2014. The outcomes of interest comprised all-cause mortality, amputation rate, ulcer healing, and ankle-brachial index (ABI). In addition, pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the safety and efficacy of the stem cell-based therapies for PAD. Thirteen studies were retrieved from 261 citations for the analysis, and in total, 527 patients (mean age: 64.2 years; median follow up: 6 months) were included in the analysis. After synthesizing data, the meta-analysis showed significant improvement in the amputation rate (OR=0.33, 95%CI=0.22-0.51; P

Myeloid-derived suppressor cells (MDSC) potently inhibit antitumor immune responses, and thereby promoti tumor progression and metastasis. However, the nature of human tumor-infiltrating MDSC remains poorly characterized. Here, we find B7-H3 is exclusively expressed on a subset of intratumoral CD14+HLA-DR−/low MDSC but absent from adjacent normal lung tissues of patients with non-small cell lung carcinoma (NSCLC). Cytokine analysis revealed that B7-H3+CD14+HLA-DR−/low MDSC (B7-H3+MDSC) produced higher levels of IL-10 and TNFα but lower levels of IL-1β and IL-6 when compared with B7-H3−CD14+HLA-DR−/low myeloid-derived suppressor cells (B7-H3−MDSC). In a murine lung cancer model, B7-H3+MDSCs were found only in the tumor microenvironment and their frequencies increased during tumor progression. Clinical data analysis indicated that a higher frequency of B7-H3+MDSCs was associated with reduced recurrence-free survival in patients with NSCLC. Taken together, we identify a novel subset of MDSCs within the tumor microenvironment that fosters tumor progression.

Objective: To explore the prehospital first-aid mode of acute cardiovascular events, management and patient prognosis. Methods: 378 patients with acute cardiovascular diseases were continuously registered at the emergency department. The patients were divided into two groups according to the different ways of prehospital care, one group included 194 patients who received first-aid care after calling ‘120’, another was a self-aid group consisting of 184 patients whom were taken to hospital by their relatives. The proportion of subjects had higher than high school education level and better knowledge for cardiovascular disease in first-aid group was higher than self-aid group (51.3 vs 28.6%, 81.0 vs 58.7%, both Pb0.05). Firstaid group received a variety of prehospital treatment, but self-aid group not. At hospital two groups were treated according to our standard procedure, then registered, and a questionnaire was taken. All patients were followed up at the end of first and third months. Results: The major cardiovascular events was myocardial infarction (58.8%) among 378 patients, there were statistically significant differences between twogroups in self-aid response time, first disposal time and prehospital rescuing time, respectively [(31.5±5.4) min vs (87.6±8.5) min, (46.1±6.9) min vs (153.9±13.4) min, (61.5±80) min vs (1539±13.4) min, all Pb0.01], but no difference in-hospital rescuing time [(29.5±5.1)min vs (32.7±4.6)min, PN0.05]. Mortality rate was lower in first-aid group than self-aid group at the end of first and thirdmonths (2.6 vs 7.6%, 4.6 vs 9.2%, both Pb0.05). Conclusion:A perfect prehospital emergency management and process can significantly reduce initial disposal time and out-hospital rescuing time of cardiovascular events, and improved the prognosis. The educational level and health knowledge of patients and their families are related to the treatment mode.