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Cedar Rapids IA 52403
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miRNA-200a/c as potential biomarker in epithelial ovarian cancer (EOC): evidence based on miRNA meta-signature and clinical investigations. - Oncotarget
Extensive effort has been put on miRNA expression signatures in epithelial ovarian cancer (EOC). Unfortunately, consistent conclusion rarely yielded from diverse studies, mainly due to the high inter-lab variability and small sample sizes. To overcome above limitations, an integrated analysis of miRNA expression signature was performed by employing Robust Rank Aggregation (RRA) method. Diagnostic analysis, Kaplan-Meier survival curves and pathway enrichment analysis were used to investigate the clinical values and biological functions of meta-signature miRNAs. A total of 519 EOC and 248 noncancerous samples were included. Seven mostly dysregulated miRNAs were identified by RRA method and two miRNAs (miR-200a-3p and miR-200c-3p) remained statistically significant after Bonferroni-correction. Diagnostic meta-analysis showed reliable diagnostic capacity of miR-200a-3p (with a pooled sensitivity of 0.84 and specificity of 0.83) and miR-200c-3p (with a pooled sensitivity of 0.75 and specificity of 0.66) for EOC. Pathway enrichment analysis and expression correlation analysis suggested miR-200a/c might contribute EOC progression by affecting cellular adhesion process. Kaplan-Meier survival analysis based on two independent cohorts revealed a strong association between miR-200a/c and overall survival in EOC patients. miR-200a/c was identified as the mostly dysregulated miRNAs in EOC and might be novel diagnostic and prognostic biomarkers for patients with EOC.
A Double-Negative Feedback Interaction between MicroRNA-29b and DNMT3A/3B Contributes to Ovarian Cancer Progression. - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Epigenetic abnormalities are increasingly observed in multiple malignancies, including epithelial ovarian cancer (EOC), and their effects can be significantly counteracted by tumor-suppressor microRNAs, namely epi-miRNAs. Here, we investigated the role of miR-29b, a well-established epi-miRNA, in the DNA methylation regulation of EOC cells.The correlation between miR-29b and DNMT3A/3B expression was evaluated by RT-qPCR, western blotting and immunohistochemical analysis. The functional roles of miR-29b and DNMT3A/3B were tested by anti-miRs and microRNA precursors. A luciferase reporter assay was employed to detect the direct binding of miR-29b to DNMT3A/3B 3' UTRs. Co-IP was utilized for investigating Id-1 binding activity.miR-29b was negatively correlated with DNMT3A/3B expression at the cellular/histological levels. miR-29b silencing was correlated with increased DNMT3A/3B levels, whereasmiR-29b over-expression caused DNMT3A/3B down-regulation. Luciferase reporter assays confirmed that the miR-29b-mediated downregulation of DNMT3A/3Boccurred through the direct targeting of theirmRNAs'3'-UTRs,whereasBGS assays found that DNMT3A/3B knockdown increased miR-29b expression via CpG island promoter hypomethylation, thus suggesting a crucial crosstalk betweenmiR-29b and DNMT3A/3B via a double-negative feedback loop. Co-IP assay confirmed direct binding between DNMT3A and Id-1.Taken together, our study sheds light on a novel epigenetic circuitry regulating EOC progression and may provide novel options for miR-29b-based epi-therapeutic approaches for future EOC treatment.Â© 2016 The Author(s) Published by S. Karger AG, Basel.
Molecular Insights into the Potential Toxicological Interaction of 2-Mercaptothiazoline with the Antioxidant Enzyme-Catalase. - International journal of molecular sciences
2-mercaptothiazoline (2-MT) is widely used in many industrial fields, but its residue is potentially harmful to the environment. In this study, to evaluate the biological toxicity of 2-MT at protein level, the interaction between 2-MT and the pivotal antioxidant enzyme-catalase (CAT) was investigated using multiple spectroscopic techniques and molecular modeling. The results indicated that the CAT fluorescence quenching caused by 2-MT should be dominated by a static quenching mechanism through formation of a 2-MT/CAT complex. Furthermore, the identifications of the binding constant, binding forces, and the number of binding sites demonstrated that 2-MT could spontaneously interact with CAT at one binding site mainly via Van der Waals' forces and hydrogen bonding. Based on the molecular docking simulation and conformation dynamic characterization, it was found that 2-MT could bind into the junctional region of CAT subdomains and that the binding site was close to enzyme active sites, which induced secondary structural and micro-environmental changes in CAT. The experiments on 2-MT toxicity verified that 2-MT significantly inhibited CAT activity via its molecular interaction, where 2-MT concentration and exposure time both affected the inhibitory action. Therefore, the present investigation provides useful information for understanding the toxicological mechanism of 2-MT at the molecular level.
Facile one-pot synthesis of highly monodisperse nickel microspheres with raised nickel dots and their adsorption performance for heavy metal ions. - Dalton transactions (Cambridge, England : 2003)
This report describes the facile solvothermal synthesis of highly monodispersed nickel microspheres with surfaces uniformly covered by nickel dots. Synthesis parameters including reaction times and reagent concentrations significantly influence the microspheric particle characteristics. The novelty of the synthetic method in this work is twofold: first, the controlled synthesis of Ni metallic microspheres using ethylene glycol as the precursor of a reductant and urea as the origin of OH(-) has never been reported. Second, there are few studies on the construction of Ni microspheres covered by uniform Ni dots using a one-step solvothermal method. Importantly, the as-prepared Ni microspheres show an improved ability to remove Cd(2+) ions even at high concentrations in water and a unique adsorption isotherm having an increasing adsorption capacity for Cd(2+) ions. The presence of Ni dots was considered to play an important role in the onset of the adsorption process. We believe that this work opens up new and possibly exciting opportunities in the field of adsorption of heavy metal ions.
The Association of Maternal Body Composition and Dietary Intake with the Risk of Gestational Diabetes Mellitus during the Second Trimester in a Cohort of Chinese Pregnant Women. - Biomedical and environmental sciences : BES
To investigate the association of maternal body composition and dietary intake with the risk of gestational diabetes mellitus (GDM).A total 154 GDM subjects and 981 controls were enrolled in a prospective cohort study in 11 hospitals from May 20, 2012 to December 31, 2013. Bioelectrical impedance analysis and dietary surveys were used to determine body composition and to evaluate the intake of nutrients in subjects at 21-24 weeks' gestation (WG). Logistic regression analysis was applied to explore the relationships of maternal body composition and dietary intake with the risk of GDM morbidity.Age, pre-pregnant body weight (BW), and body mass index (BMI) were associated with increased risk of GDM. Fat mass (FM), fat mass percentage (FMP), extracellular water (ECW), BMI, BW, energy, protein, fat, and carbohydrates at 21-24 WG were associated with an increased risk of GDM. In contrast, fat free mass (FFM), muscular mass (MM), and intracellular water (ICW) were associated with a decreased risk of GDM.Maternal body composition and dietary intake during the second trimester of pregnancy were associated with the risk of GDM morbidity.Copyright Â© 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.
Prognostic value of natriuretic peptides in severe trauma patients with multiple organ dysfunction syndrome. - Experimental and therapeutic medicine
The aim of the present study was to evaluate the prognostic values of the N-terminal peptide of pro-atrial natriuretic peptide (NT-proANP) and the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) in severe trauma patients developing multiple organ dysfunction syndrome (MODS). Out of the 126 severe trauma patients that were admitted to the Emergency Intensive Care Unit of the General Hospital of Shenyang Military Region between January 2009 and December 2011, 26 patients with multiple injuries and an injury severity score (ISS) of >16 points were included in the study. The MODS score was calculated on admission as well as 24, 48 and 72 h after the injury. Patients were divided into two groups: Group A consisted of patients with minor signs of organ dysfunction (MODS score, â‰¤4 points) and group B of patients with major organ dysfunction (MODS score, >4 points). Venous blood (5 ml) was extracted from the patients on admission and 6, 12, 24, 48 and 72 h after the injury. The Elecsys proBNPÂ® and proANPÂ® assays were used to determine the NT-proBNP and NT-proANP levels, respectively. The changes in the levels of C-reactive protein, white blood cells and neutrophils were detected and analyzed on admission. Acute physiology and chronic health evaluation II scores and ISSs were collected 72 h after the injury. The hemodynamic monitoring of cardiac index (CI) was performed using The Pulse index Continuous Cardiac Output system. The serum NT-proANP and NT-proBNP concentrations were elevated in all 26 patients. Upon admission, the serum NT-proANP and NT-proBNP values were 637.3Â±8.9 and 137.3Â±8.9 pmol/l, respectively, in group A and 1,185.0Â±7.2 and 185.0Â±7.2 pmol/l, respectively, in group B. The NT-proANP and NT-proBNP levels in group A were significantly lower than those in group B at all subsequent time-points (P<0.001). By contrast, the CI in group A was significantly higher than that in group B at all time-points (P<0.001). An inverse correlation was observed between the NT-proANP or NT-proBNP concentration and CI at 24, 48 and 72 h after the injury (r=-0.679 and -0.772, respectively; P<0.001). In conclusion, the serum NT-proANP and NT-proBNP concentrations following multiple injuries have been found to be significantly correlated with the clinical signs of MODS, and a distinct correlation has been observed between the levels of serums NT-proANP and NT-proBNP and decreased CI. The data of this pilot study suggest that NT-proANP and NT-proBNP levels may be of value in the diagnosis of post-traumatic cardiac impairment.
MicroRNA-29B (mir-29b) regulates the Warburg effect in ovarian cancer by targeting AKT2 and AKT3. - Oncotarget
Epithelial ovarian cancer (EOC) is the most lethal and aggressive gynecological malignancy, and abnormal cellular metabolism significantly contributes to cancer onset and progression. Here, we report that miR-29b negatively regulates AKT2/AKT3 expression, causing HK2/PKM2 downregulation and leading to a decreased Warburg effect and slowed ovarian cancer progression. Compared to normal ovaries, ovaries with epithelial cancer exhibited lower miR-29b expression at both cellular/histological levels. Glucose consumption and lactate production experiments confirmed miR-29b's regulation of EOC metabolism. A luciferase reporter assay confirmed the direct binding of miR-29b to AKT2/AKT3 3' UTRs. miR-29b silencing correlated with increased expression of AKT2/3, pAKT2/3, HK2, and PKM2. Pyruvic acid and NAD+/NADH levels also changed when miR-29b expression was suppressed; this effect could be blocked by specific AKT inhibitors, suggesting the miR-29b-AKT axis regulates the Warburg effect in ovarian cancer. In xenograft mouse models, miR-29b inhibited tumor formation in vivo. In vivo imaging also demonstrated that miR-29b agomir inhibited the relative uptake of 18F-FDG in the xenograft tumors, suggesting that miR-29b over-expression could negatively modulate tumor glucose metabolism in vivo. Taken together, our study suggests that miR-29b regulates the Warburg effect in EOC via AKT2/AKT3 and may provide novel options for future treatments for EOC.
Construction of Cu3Mo2O9 nanoplates with excellent lithium storage properties based on a pH-dependent dimensional change. - Dalton transactions (Cambridge, England : 2003)
One-, two- and three-dimensional nanostructures of copper molybdenum oxide hydroxide were successfully constructed by a simple approach through a pH-dependent dimensional transformation of ammonium copper molybdate. Thin nanoplates of copper molybdate, which were obtained by sintering the two-dimensional nanobelts of copper molybdenum oxide hydroxide, exhibited remarkably high reversible lithium storage capacity, good rate capability and excellent cycling stability.
Systematic Genome-wide Screening and Prediction of microRNAs in EBOV During the 2014 Ebolavirus Outbreak. - Scientific reports
Recently, several thousand people have been killed by the Ebolavirus disease (EVD) in West Africa, yet no current antiviral medications and treatments are available. Systematic investigation of ebolavirus whole genomes during the 2014 outbreak may shed light on the underlying mechanisms of EVD development. Here, using the genome-wide screening in ebolavirus genome sequences, we predicted four putative viral microRNA precursors (pre-miRNAs) and seven putative mature microRNAs (miRNAs). Combing bioinformatics analysis and prediction of the potential ebolavirus miRNA target genes, we suggest that two ebolavirus coding possible miRNAs may be silence and down-regulate the target genes NFKBIE and RIPK1, which are the central mediator of the pathways related with host cell defense mechanism. Additionally, the ebolavirus exploits the miRNAs to inhibit the NF-kB and TNF factors to evade the host defense mechanisms that limit replication by killing infected cells, or to conversely trigger apoptosis as a mechanism to increase virus spreading. This is the first study to use the genome-wide scanning to predict microRNAs in the 2014 outbreak EVD and then to apply systematic bioinformatics to analyze their target genes. We revealed a potential mechanism of miRNAs in ebolavirus infection and possible therapeutic targets for Ebola viral infection treatment.
Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone. - Nature
A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 Ã— 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 Ã— 10(-3) to 1.41 Ã— 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics.
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1201 3Rd Ave Se Cedar Rapids, IA 52403
202 10Th Street Se
202 10Th St Se Suite 225
1030 5Th Ave Se Suite 1400
701 10Th St Se J Edward Lundy Pavilion 4Th Floor