Correlation of epicardial adipose tissue and inflammatory indices in patients with STEMI and implications for atrial arrhythmias.

BACKGROUND: Epicardial adipose tissue(EAT) is associated with inflammation in previous studies but is unknown in patients with ST-segment elevation myocardial infarction(STEMI).This study investigated the correlation between epicardial fat and inflammatory cells obtained by cardiac magnetic resonance (CMR) and the effect on atrial arrhythmias in patients with STEMI. METHODS: This was a single-center, retrospective study. We consecutively selected patients who all completed CMR after Percutaneous Coronary Intervention (PCI) from January 2019 to December 2022 and then had regular follow-ups at 1, 3, 6, 9, and 12 months. The enrolled patients were grouped according to the presence or absence of atrial arrhythmia and divided into atrial and non-atrial arrhythmia groups. RESULTS: White blood cell, neutrophil, lymphocyte, C-reactive protein, EATV, LVES, LVED were higher in the atrial arrhythmia group than in the non-atrial arrhythmia group, and LVEF was lower than that in the non-atrial arrhythmia group (p < 0.05); EATV was significantly positively correlated with each inflammatory indices (white blood cell: r = 0.415 p < 0.001, neutrophil:r = 0.386 p < 0.001, lymphocyte:r = 0.354 p < 0.001, C-reactive protein:r = 0.414 p < 0.001); one-way logistic regression analysis showed that risk factors for atrial arrhythmias were age, heart rate, white blood cell, neutrophil, lymphocyte, C-reactive protein, EATV, LVES, LVED; multifactorial logistic regression analysis showed that neutrophil, lymphocyte, C-reactive protein, EATV, and LVES were independent risk factors for atrial arrhythmias; ROC analysis showed that the area under the curve (AUC) for neutrophil was 0.862; the AUC for lymphocyte was 1.95; and the AUC for C-reactive protein was 0.862. reactive protein was 0.852; AUC for LVES was 0.683; and AUC for EATV was 0.869. CONCLUSION: In patients with STEMI, EAT was significantly and positively correlated with inflammatory indices; neutrophil, lymphocyte, C-reactive protein, EATV, and LVES were independent risk factors for atrial arrhythmias and had good predictive value.

Assessment of TUFT1 and Rac1-GTP levels in triple-negative breast cancer patients: clinical and pathological correlations.

OBJECTIVE: The primary goal of this study was to investigate the expressions of TUFT1 (Tuftelin) and Rac1-GTP in the cancerous tissues of individuals with triple-negative breast cancer (TNBC). Additionally, we aimed to explore the correlation between TUFT1 and Rac1-GTP expressions and examine the associations of TUFT1 and Rac1-GTP expressions with the clinical and pathological indicators of the patients. METHODS: Ninety-six patients diagnosed with TNBC, scheduled for surgery between May 2022 and November 2022, were enrolled in this study. Cancerous tissue specimens were collected from these patients, and immunohistochemistry was employed to evaluate the levels of TUFT1 and Rac1-GTP expressions in the cancerous tissues. Subsequent to data collection, a comprehensive analysis was conducted to examine the correlation between TUFT1 and Rac1-GTP expressions. Furthermore, we sought to assess the associations of TUFT1 and Rac1-GTP expressions with the clinical and pathological indicators of the patients. RESULTS: The TUFT1 protein was expressed in both the membrane and cytoplasm of TNBC cancer cells, with notably higher expression observed in the cytoplasm. Rac1-GTP was primarily expressed in the cytoplasm. There was a positive correlation between the levels of TUFT1 and Rac1-GTP expressions (χ2 = 9.816, P < 0.05). The levels of TUFT1 and Rac1-GTP protein expressions showed no correlation with patient age (χ2 = 2.590, 2.565, P > 0.05); however, they demonstrated a positive correlation with tumor size (χ2 = 5.592,5.118), histological grading (χ2 = 6.730, 5.443), and lymph node metastasis (χ2 = 8.221, 5.180) (all with a significance level of P < 0.05). CONCLUSION: A significant correlation was identified between the levels of TUFT1 and Rac1-GTP expressions in the cancerous tissues of patients with TNBC, suggesting a close association with the progression of TNBC. The two molecules play significant roles in facilitating an early diagnosis and treatment of TNBC.

Instant mucus dressing of PEO reinforced by chitosan nanofiber scaffold for open wound healing.

Dressings seamlessly attached to the open wound bed are necessary for fully unleashing the dressing healing ability, as leaving the voids beneath the dressing poses infection hazards. The present study prepared an instant mucus dressing (IMD) of polyethylene oxide (PEO) reinforced by chitosan (CS) nanofiber scaffold, which formed by immersing PEO/CS nanofiber mat in water. The PEO/CS nanofiber mat were fabricated by the solution blow spinning (SBS) method using PEO and CS mixed solutions. Attenuated total reflection Fourier transform infrared spectroscopy (FTIR-ATR), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and differential scan calorimetry (DSC) analyses indicate that PEO macromolecules formed the most of nanofiber shell due to their lower surface tension while CS macromolecules stayed mainly inside the fiber as the core. When such a PEO/CS nanofiber mat was immersed in water, PEO swelled to form mucus dressing reinforced by CS inside the nanofiber, which was fluidic and able to fully fill the voids on the wound. In vivo rat experiment verified that the dressing significantly accelerated the open wound healing through seamlessly attaching of mucus to the open wound and providing moist environment. The dressings exhibit good platelets and whole blood cells adhesion properties, excellent hemostasis function and no cytotoxicity. This instant mucus dressing provided a new perspective for manufacturing high performance open wound dressings.

Left atrial strain associated with interatrial block in patients with ST-segment elevation myocardial infarction.

Both interatrial block (IAB) and left atrium (LA) strain are associated with atrial arrhythmias in ST-segment elevation myocardial infarction (STEMI) patients, but the relationship between IAB and LA strain has not yet been reported. This study was to investigate the correlation between LA strain and IAB in STEMI patients. This is a single-center retrospective clinical observational study. The STEMI patients with primary percutaneous coronary intervention (pPCI) were enrolled, and all patients completed cardiac magnetic resonance (CMR). A standard 12-lead electrocardiogram (ECG) was recorded on the same day as CMR. IAB was measured by p duration on ECG at follow-up. 302 patients were enrolled, including 91 (30.1%) with IAB. The reservoir strain, conduit strain and booster strain were included in model 1, model 2 and model 3, respectively. In model 1, age (OR 1.025; 95%CI 1.003-1.047; p = 0.026), hypertension (OR 2.188; 95%CI 1.288-3.719; p = 0.004), and reservoir strain (OR 0.947; 95%CI 0.920-0.974; p < 0.001) were independent factors for IAB. In model 2, age (OR 1.031; 95%CI 1.009-1.053; p = 0.006), hypertension (OR 2.058; 95%CI 1.202-3.522; p = 0.008), RCA lesions (OR 1.797; 95%CI 1.036-3.113; p = 0.037), and conduit strain (OR 0.910; 95%CI 0.868-0.953; p < 0.001) were independent factors for IAB. In model 3, age (OR 1.022; 95%CI 1.001-1.045; p = 0.044), hypertension (OR 2.239; 95%CI 1.329-3.773; p = 0.002), and booster strain (OR 0.948; 95%CI 0.908-0.991; p = 0.019) were independent factors for IAB. With the lowest AIC and BIC values, model 2 was the best-fit model. LA strain associated with IAB in STEMI patients. The model including conduit strain was the best-fit one.

Coronary Angiography-Derived Index of Microcirculatory Resistance Associated With New-Onset Atrial Fibrillation in Patients With STEMI.

BACKGROUND: Coronary angiography-derived index of microcirculatory resistance (caIMR) can effectively assess coronary microvascular dysfunction in patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to explore the role of caIMR in the occurrence of new-onset atrial fibrillation (NOAF) in patients with STEMI. METHODS: This was a single-centre retrospective clinical observational study. Patients diagnosed with STEMI from September 2019 to December 2022 were included. caIMR was calculated using computational flow and pressure simulations. During admission, suspicious heart rhythm was recorded by electrocardiographic (ECG) monitoring, and NOAF was confirmed by an immediate 12-lead ECG. RESULTS: A total of 739 patients were enrolled, including 57 (7.7) with NOAF. caIMR was significantly correlated with microvascular obstruction (R = 0.604; P < 0.001) and infarct size (R = 0.514; P < 0.001). After adjusting for potential confounding factors, the results showed that caIMR (odds ratio 1.058, 95% confidence interval 1.035-1.083; P < 0.001) was an independent risk factor for NOAF in patients with STEMI. Receiver operating characteristic analysis showed that the area under the curve of caIMR for predicting NOAF was 0.716. Compared with the caIMR < 27.35 U group, the caIMR ≥ 27.35 U group had higher high-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide levels. When caIMR was added to the model, the reclassification and discriminant abilities improved significantly. CONCLUSIONS: Higher caIMR was an independent risk factor for NOAF in patients with STEMI. The caIMR had high specificity and sensitivity for predicting NOAF in patients with STEMI. The integration of caIMR into clinical risk factors showed significantly increased predictability for NOAF in patients with STEMI.

Prognostic significance of long non coding maternally expressed gene 3 in pediatric acute myeloid leukemia.

ABSTRACT: The purpose of this study was to evaluate the correlation of long non-coding RNA maternally expressed gene 3 (Lnc-MEG3) with disease features, treatment response, and survival in pediatric acute myeloid leukemia (AML) patients.Among 92 de novo pediatric AML patients (before treatment and after 1 course of induction) and 40 controls, bone marrow mononuclear cells were obtained. Then, Lnc-MEG3 expression was determined by reverse transcription quantitative polymerase chain reaction. After 1 course of standard induction therapy of pediatric AML patients, complete remission (CR) was assessed. Furthermore, event-free survival (EFS) and overall survival (OS) were determined according to follow-up data.Lnc-MEG3 was reduced in pediatric AML patients compared with controls. In pediatric AML patients, Lnc-MEG3 was correlated with French-American-Britain subtypes and lower Chinese Medical Association risk stratification, while it was not associated with cytogenetic features, FLT3-ITD mutation, CEBPA mutation, NPM1 mutation, WT1 mutation, or National Comprehensive Cancer Network risk stratification. After 1 course of treatment, Lnc-MEG3 exhibited an up-regulation trend. Furthermore, Lnc-MEG3 was of no difference before treatment between patients with and without CR, while elevated Lnc-MEG3 and change of Lnc-MEG3 after 1 course of treatment were associated with increased CR rate. Additionally, increased Lnc-MEG3 expression before treatment was associated with longer EFS but not OS, while enhanced Lnc-MEG3 expression after 1 course of treatment was correlated with both prolonged EFS and OS.Lnc-MEG3 may have clinical significance as a biomarker for assisting with disease management, treatment optimization, and prognosis improvement in pediatric AML patients.

IncRNA MVIH correlates with disease features, predicts treatment response and survival in pediatric acute myeloid leukemia.

OBJECTIVE: Long non-coding RNA microvascular invasion in hepatocellular carcinoma (lnc-MVIH) is correlated with unfavorable prognosis in several malignancies, while limitedly studied in pediatric acute myeloid leukemia (AML). This study aimed to investigate the correlation of lnc-MVIH with disease features, response to induction therapy, and survival in pediatric AML patients. METHODS: A total of 129 de novo pediatric AML patients who were retrospectively analyzed and 60 children with non-malignant hematological diseases who underwent bone marrow examination were reviewed as controls. Bone marrow mononuclear cells (BMMCs) were isolated from all participants to detect lnc-MVIH expression by reverse transcription-quantitative polymerase chain reaction. The complete remission status after 1 course of induction therapy, event-free survival, and overall survival of pediatric AML patients were recorded. RESULTS: Lnc-MVIH was upregulated in pediatric AML patients compared with controls (p < 0.001). In pediatric AML patients, lnc-MVIH was correlated with increased bone marrow blasts, less inv(16) or t(16;16) abnormity, and higher Chinese Medical Association (CMA) risk stratification (all p < 0.05), whereas its correlation with National Comprehensive Cancer Network (NCCN) risk stratification was not statistically significant (p = 0.098). As for prognosis, lnc-MVIH high expression patients presented with lower complete response rate to 1 course of induction therapy (61.5% vs. 79.7%, p = 0.024), shorter event-free survival (median 12.0 months vs. 22.0 months, p = 0.006), and overall survival (median 28.0 months vs. 42.0 months, p = 0.043) compared with lnc-MVIH low expression patients. CONCLUSION: Lnc-MVIH correlates with poor treatment response and unfavorable survival in pediatric AML.

Effect of Steel Slag Aggregate on Pavement and Flame-Retardant Performance of Warm-Mixed Flame-Retardant Asphalt Concrete.

With the rapid development of tunnel construction, tunnel safety and the shortage of high-quality aggregates have concerned researchers so that this issue has become a research hot spot in the past few years. In the present study, we intended to prepare warm-mixed flame-retardant asphalt concrete using steel slag aggregate and evaluate its pavement and flame retardant performance. In this regard, the chemical composition and microstructure of the steel slag were studied using X-ray fluorescence analysis (XRF) and scanning electron microscopy (SEM). Then diverse pavement performances, including the dynamic stability, immersion Marshall, freeze-thaw splitting strength and low-temperature bending, were investigated for the warm-mixed flame-retardant asphalt concrete with steel slag aggregate. Moreover, a creative method of the flame spray gun combustion test was proposed to characterize the combustion degree and evaluate the flame-retardant performance of the asphalt concrete with steel slag. The experimental results show that the high-temperature and moisture stability performance are improved due to the addition of steel slag, however, the low-temperature performance is reduced for the warm-mixed flame-retardant asphalt concrete while it is still higher than the requirement value of the Chinese specification (GB/T 30596-2014). Meanwhile, the ignition temperature is increased and the ignition time is delayed for warm-mixed flame-retardant asphalt concrete because of the addition of steel slag. It is concluded that asphalt concrete with steel slag has excellent flame-retardant performance so that it is an appropriate choice for tunnel pavement.

Effect of Diethylene Glycol on the Inkjet Printability of Reactive Dye Solution for Cotton Fabrics.

Digital inkjet printing technology plays an increasingly important role in textile printing. The printing printability of reactive dye inks is the key to improving the quality of printed fabrics. In this study, an eco-friendly and simple method to improve the inkjet printability of reactive dye solutions was proposed. The influence of diethylene glycol on the surface tension, rheology, and dye molecule aggregation properties for three reactive dye solutions was investigated. The jetting performance of dye solutions was explored by observing droplet formation. Moreover, the color performance of printed cotton fabrics, including reactive dye solution penetration, colorimetric values, and color strength, was evaluated. Addition of diethylene glycol could change the aggregation of dye molecules by hydrophobic forces and hydrogen bonds. Diethylene glycol could inhibit formation of satellite droplets by changing the viscosity and surface tension of solutions, which made the pattern printed on cotton fabrics show regular edge sharpness. Furthermore, the dye solutions containing 10% DEG not only satisfied various properties of reactive dye inks but also had the highest color strength and the deepest and brightest colors.

Green and Efficient Inkjet Printing of Cotton Fabrics Using Reactive Dye@Copolymer Nanospheres.

Digital inkjet printing of textiles possesses great advantages like high efficiency and flexible production, but the challenges like the risk of causing serious environmental problems due to the large usage of dyes and chemicals still remain a matter of concern. In response to this problem, herein, a novel kind of reactive dye@copolymer nanosphere was prepared through the adsorption of C. I. Reactive Red 218 dyes (RR218) onto cationic poly(styrene-butyl acrylate-vinylbenzyl trimethylammonium chloride) (PSBV) nanospheres and applied in inkjet printing on woven cotton fabric. Results show that the prepared RR218@PSBV nanospheres possessed homogeneous size and good stability for ink preparation. In comparison with the original RR218 solution, the color depth of RR218@PSBV-printed fabric increased by 1.4 times and the dye residues in the printing effluent were reduced by about 45%. Meanwhile, the consumptions of sodium carbonate and urea in conventional inkjet printing were reduced by about 3.3 and 22.8 mg/cm2, respectively, and the printing process was simplified with 30% energy saving. Furthermore, the mechanism of the color enhancement by nanospheres was revealed by the calculation of absorption and scattering coefficients based on the Kubelka-Munk function. This work provides a potential application of dye@polymer nanospheres to promote the optimization of the textile inkjet printing technique and alleviates the environmental impact of conventional textile coloration.

Eco-dyeing with biocolourant based on natural compounds.

Biomass pigments have been regarded as promising alternatives to conventional synthetic dyestuffs for the development of sustainable and clean dyeing. This investigation focused on in situ dyeing of fabrics with biopigments derived from tea polyphenols via non-enzymatic browning reaction. The average particle size of dyed residual liquor with natural tea polyphenol was 717.0 nm (ranging from 615.5 to 811.2 nm), and the Integ value of dyed wool fabrics was the greatest compared to those of counterparts. In addition, the Integ values of dyed fabrics with residual liquor were much bigger than those with the first reaction solutions when dyed by identical dyeing liquor. As a result, the dyeing process could be carried out many times because the concentration of the residual liquor was relatively superior. All dyed fabrics acquired admirable rubbing as well as washing fastness, and the relevant dyeing mechanism has been analysed in the paper.

Preparation of Biocolorant and Eco-Dyeing Derived from Polyphenols Based on Laccase-Catalyzed Oxidative Polymerization.

Natural products have been believed to be a promising source to obtain ecological dyes and pigments. Plant polyphenol is a kind of significant natural compound, and tea provides a rich source of polyphenols. In this study, biocolorant derived from phenolic compounds was generated based on laccase-catalyzed oxidative polymerization, and eco-dyeing of silk and wool fabrics with pigments derived from tea was investigated under the influence of pH variation. This work demonstrated that the dyeing property was better under acidic conditions compared to alkalinity, and fixation rate was the best when pH value was 3. Furthermore, breaking strength of dyed fabrics sharply reduced under the condition of pH 11. Eventually, the dyeing method was an eco-friendly process, which was based on bioconversion, and no mordant was added during the process of dyeing.

Inkjet Printable and Self-Curable Disperse Dyes/P(St-BA-MAA) Nanosphere Inks for Both Hydrophilic and Hydrophobic Fabrics.

Low-water-soluble disperse dyes possess a broad color gamut and good durability, but they need chemical or physical modification before being used in inks and can only be applied to several kinds of hydrophobic fabrics. In this work, disperse dyes/P(St-BA-MAA) nanospheres (known as DPN) absorbed by sodium nitrilotriacetate (known as NTA@DPN) were prepared and applied into ink formulations, which exhibited high dye fixation, long-term stability and self-curable ability without addition of any binder. Transmission electron microscopy (TEM) images showed the nanospheres have homogeneous core-shell spherical shape and the average diameter increased by 20.6 nm after coloration. X-ray diffraction (XRD), Fourier transform infrared spectrum (FTIR), and differential scanning calorimetry (DSC) measurements illustrated the interaction between dyes and nanospheres and indicated that the colored nanospheres contained both dye molecules and crystalline dyes. The Zeta potential and particle size measurements demonstrated that the dispersion stability was improved when sodium nitrilotriacetate (NTA) was absorbed onto DPN. The rheological behavior of the NTA@DPN inks was Newtonian and desired droplet formation was achieved at the viscosity of 4.23 mPa·s. Both hydrophilic cotton and hydrophobic polyester fabrics were cationic modified before used, which had an excellent image quality and desired rubbing fastness after inkjet printing. Scanning electron microscope (SEM) images showed NTA@DPN formed stable deposits on the surface of modified fibers and could self-cure to form continuous film coating on the fiber surface after being baked at 150 °C without addition of any binder.

Visible light-induced cyclization reactions for the synthesis of 1,2,4-triazolines and 1,2,4-triazoles.

A novel method for concisely synthesizing 1,2,4-triazolines via [3+2] cyclization under visible light is reported. These compounds can be easily converted into 1,2,4-triazoles under basic or photoredox conditions. The application of the 1,2,4-triazoles was also investigated via mild operations.

pH-Mediated Antibacterial Dyeing of Cotton with Prodigiosins Nanomicelles Produced by Microbial Fermentation.

This study developed a novel pH-mediated antimicrobial dyeing process of cotton with prodigiosins nanomicelles produced by microbial fermentation. The average diameter of the pigment nanomicelles was 223.8 nm (range of 92.4⁻510.2 nm), and the pigment concentration was 76.46 mg/L. It was found that the superior dyeing effect of cotton fabric was achieved by adjusting the dye bath pH. When the pH was three, dyed cotton under 90 °C for 60 min exhibited the greatest color strength with good rubbing, washing and perspiration color fastness. By the breaking strength test and XRD analysis, it was concluded that the cotton dyed under the optimum condition almost suffered no damage. In addition, due to the presence of prodigiosins, dyed cotton fabric under the optimal process showed outstanding bacteriostatic rates of 99.2% and 85.5% against Staphylococcus aureus and Escherichia coli, respectively. This research provided an eco-friendly and widely-applicable approach for antimicrobial intracellular pigments with the property of pH-sensitive solubility in water to endow cellulose fabric with color and antibacterial activity.

Fluorescent Nanocomposite for Visualizing Cross-Talk between MicroRNA-21 and Hydrogen Peroxide in Ischemia-Reperfusion Injury in Live Cells and In Vivo.

MicroRNAs (miRNAs) and reactive oxygen species (ROS) are concurrently implicated in heart ischemia-reperfusion (IR) injury. There may exist mutual cross-talk between miRNAs and ROS in cardiac IR injury process. In this study, we developed a novel crown-like silica@polydopamine-DNA-CeO2 nanocomposite by assembly of silica@polydopamine-DNA1 nanoparticles decorated with satellite CeO2-DNA2 nanoparticles for detecting and imaging of microRNA-21 (miR-21) and hydrogen peroxide (H2O2) in simulated IR injury in living cells and in vivo. The miRNA-21 was found to be regulated by H2O2 via PI3K/AKT signaling pathway for the first time in H9C2 cells in simulated ischemia-reperfusion injury. H2O2 and miRNA-21 are overproduced during mimicked heart ischemia-reperfusion injury, suggesting that they are closely related to reperfusion injury. All these results reveal that there is definite cross-talk between miR-21 and H2O2 in IR injury. The current method can provide a promising strategy to further explore the interplaying roles between ROS and miRNAs in other pathological processes.

[Association between CYP1A1*2A polymorphism and susceptibility to childhood acute lymphoblastic leukemia: a Meta analysis].

OBJECTIVE: To explore the association between CYP1A1*2A polymorphism and susceptibility to childhood acute lymphoblastic leukemia (ALL) through a Meta analysis. METHODS: Inclusion and exclusion criteria were formulated and English and Chinese databases (PubMed, OVID Database, CBM, CNKI, and Wanfang Data) were searched comprehensively. The studies (from January 1999 to April 2015) related to the association between CYP1A1*2A polymorphism and susceptibility to childhood ALL were collected. STATA 12.0 Software was applied to perform the Meta analysis for the articles included. RESULTS: A total of 12 articles were included for analysis (11 English articles and 1 Chinese article), which involved 3 355 cases in total. The results of the Meta analysis showed a significant association between CYP1A1*2A polymorphism and susceptibility to childhood ALL (allele model: OR=1.31, 95% CI: 1.07-1.61; dominant model: OR=1.33, 95% CI: 1.13-1.56; codominant model: OR=1.30, 95% CI: 1.10-1.54). According to the results of a subgroup analysis based on ethnic origin, an increased risk of childhood ALL was observed in both Asian subgroup (dominant model: OR=1.57, 95% CI: 1.19-2.08; codominant model: OR=1.61, 95% CI: 1.20-2.17) and the Caucasian subgroup (allele model: OR=1.31, 95% CI: 1.04-1.63; dominant model: OR=1.22, 95% CI: 1.00-1.49). CONCLUSIONS: CYP1A1*2A polymorphism may be associated with the genetic susceptibility to childhood ALL.

Quantitative nuclear proteomics identifies that miR-137-mediated EZH2 reduction regulates resveratrol-induced apoptosis of neuroblastoma cells.

Neuroblastoma is the most common pediatric extracranial solid tumor with a broad spectrum of clinical behavior and poor prognosis. Despite intensive multimodal therapy, ongoing clinical trials, and basic science investigations, neuroblastoma remains a complex medical challenge with a long-term survival rate less than 40%. In our study, we found that resveratrol (3, 5, 4'-trihydroxystilbene, RSV), a naturally occurring phytoalexin, possesses an anticancer activity through blocking cell growth and inducing apoptosis in neuroblastoma cell line Neuro-2a (N-2a) cells. Using stable isotope labeling with amino acids in cell culture (SILAC) and quantitative proteomic analysis, we found that 395 proteins were up-regulated and 302 proteins were down-regulated in the nucleus of N-2a cells treated with RSV. Among these, the polycomb protein histone methyltransferase EZH2 was reduced significantly, which is aberrantly overexpressed in neuroblastoma and crucial to maintain the malignant phenotype of neuroblastoma by epigenetic repression of multiple tumor suppressor genes. EZH2 reduction further led to decreased H3K27me3 level and reactivation of neuroblastoma tumor suppressor genes CLU and NGFR. Disruption EZH2 expression by RNA interference-mediated knockdown or pharmacologic inhibition with DZNep triggered cellular apoptosis in N-2a cells. We found that the up-regulation of miR-137 level was responsible for reduced EZH2 level in tumor suppression induced by RSV. Inhibition of miR-137 expression rescued the cellular apoptosis phenotypes, EZH2 reduction, and CLU and NGFR reactivation, associated with RSV treatment. Taken together, our findings present for the first time, an epigenetic mechanism involving miR-137-mediated EZH2 repression in RSV-induced apoptosis and tumor suppression of neuroblastoma, which would provide a key potential therapeutic target in neuroblastoma treatment.

[Correlations between 6-mercaptopurine treatment-related adverse reactions in children with acute lymphoblastic leukemia and polymorphisms of thiopurine methyltransferase gene].

OBJECTIVE: To explore 6-mercaptopurine (6-MP) treatment-related adverse reactions in children with acute lymphoblastic leukemia (ALL), and to assess the association between the polymorphisms of thiopurine methyltransferase (TPMT) gene and these 6-MP related toxicities. METHODS: Total RNA was extracted from bone marrow samples of 46 children with ALL and was then reversed to cDNA. TPMT(*)1S and (*)3C were screened by denaturing gradient gel electrophoresis (DGGE) combining with DNA sequencing. Drug toxicities were classified according to national cancer institute-common toxicity criteria version 3.0 (NCI CTC 3.0). The relationship between TPMT gene polymorphisms and the adverse reactions of 6-MP treatment was analyzed. RESULTS: During the maintenance treatment period, 22% (10/46) of children discontinued 6-MP treatment because of serious adverse reactions. Two children with TPMT(*)3C genotypes presented severe adverse reactions, including 1 child with homozygotic mutation who had 6-MP dose-related myelosuppression and hepatotoxicity. The main side effects of 6-MP were myelosuppression, hepatotoxicity and gastrointestinal reaction. And there were no significant differences between TPMT(*)1S genotypes and severe myelosuppression or hepatotoxicity caused by 6-MP (P>0.05). CONCLUSIONS: TPMT(*)3C may correlate with severe adverse reactions caused by 6-MP.

Distinguishing transgenic from non-transgenic Arabidopsis plants by (1)H NMR-based metabolic fingerprinting.

We have recently reported the construction of an nuclear magnetic resonance (NMR)-based metabonomics study platform, Automics. To examine the application of Automics in transgenic plants, we performed metabolic fingerprinting analysis, i.e., (1)H NMR spectroscopy and multivariate analysis, on wild-type and transgenic Arabidopsis. We found that it was possible to distinguish wild-type from four transgenic plants by PLS-DA following application of orthogonal signal correction (OSC). Scores plot following OSC clearly demonstrates significant variation between the transgenic and non-transgenic groups, suggesting that the metabolic changes among wild-type and transgenic lines are possibly associated with transgenic event. We also found that the major contributing metabolites were some specific amino acids (i.e., threonine and alanine), which could correspond to the insertion of the selective marker BAR gene in the transgenic plants. Our data suggests that NMR-based metabonomics is an efficient method to distinguish fingerprinting difference between wild-type and transgenic plants, and can potentially be applied in the bio-safety assessment of transgenic plants.