Concomitant hypermethylation of multiple genes in non-small cell lung cancer (NSCLC)

Primary lung cancer remains the leading cause of cancer death worldwide. Promoter hypermethylation is a major inactivation mechanism of tumor-related genes, and increasingly appears to play an important role in carcinogenesis. In the present study, we used quantitative methylation-specific PCR (Q-MSP) assays to analyze promoter hypermethylation of nine genes in a large cohort of well-characterized non-small cell lung cancer (NSCLC) and explore their associations with the clinicopathological features of tumor. We found that there were significant differences in methylation levels for six of nine gene promoters between cancerous and noncancerous lung tissues. More importantly, with 100% diagnostic specificity, high sensitivity, ranging from 44.9% to 84.1%, was found for each of the nine genes. Interestingly, promoter hypermethylation of most genes was closely associated with histologic type, which was more frequent in squamous cell carcinomas (SCC) than in adenocarcinomas (ADC). In addition, highly frequent concomitant methylation of multiple genes was found in NSCLC, particularly in SCC. Our data showed that multiple genes were aberrantly methylated in lung tumorigenesis, and that they were closely associated with certain clinicopathological features of NSCLC, particularly of the histologic type, suggesting that these hypermethylated genes could be potential biomarkers in early detection of NSCLC in high-risk individuals, as well as in evaluating the prognosis of NSCLC patients. (Folia Histochemica et Cytobiologica 2011, Vol. 49, No. 1, 132–141

Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC)

<p>Abstract</p> <p>Background</p> <p>Lung cancer is the leading cause of cancer-related death worldwide. Genetic and epigenetic alterations have been identified frequently in lung cancer, such as promoter methylation, gene mutations and genomic amplification. However, the interaction between genetic and epigenetic events and their significance in lung tumorigenesis remains poorly understood.</p> <p>Methods</p> <p>We determined the promoter methylation of 6 genes and <it>PIK3CA </it>amplification using quantitative methylation-specific PCR (Q-MSP) and real-time quantitative PCR, respectively, and explore the association of promoter methylation with <it>PIK3CA </it>amplification in a large cohort of clinically well-characterized non-small cell lung cancer (NSCLC).</p> <p>Results</p> <p>Highly frequent promoter methylation was observed in NSCLC. With 100% diagnostic specificity, excellent sensitivity, ranging from 45.8 to 84.1%, was found for each of the 6 genes. The promoter methylation was associated with histologic type. Methylation of <it>CALCA, CDH1, DAPK1</it>, and <it>EVX2 </it>was more common in squamous cell carcinomas (SCC) compared to adenocarcinomas (ADC). Conversely, there was a trend toward a higher frequency of <it>RASSF1A </it>methylation in ADC than SCC. In addition, <it>PIK3CA </it>amplification was frequently found in NSCLC, and was associated with certain clinicopathologic features, such as smoking history, histologic type and pleural indentation. Importantly, aberrant promoter methylation of certain genes was significantly associated with <it>PIK3CA </it>amplification.</p> <p>Conclusions</p> <p>Our data showed highly frequent promoter methylation and <it>PIK3CA </it>amplification in Chinese NSCLC population, and first demonstrated the associations of gene methylation with <it>PIK3CA </it>amplification, suggesting that these epigenetic events may be a consequence of overactivation of PI3K/Akt pathway.</p

Preparation, Characterization, and Application of Magnetic Fe-SBA-15 Mesoporous Silica Molecular Sieves

Magnetic Fe-SBA-15 mesoporous silica molecular sieves were prepared, characterized, and used for magnetic separation. Wet impregnation, drying, and calcination steps led to iron inclusion within the mesopores. Iron oxide was reduced to the metal form with hydrogen, and the magnetic Fe-SBA-15 was obtained. Fourier-transform infrared spectroscopy confirmed the preparation process from the oxide to metal forms. The structure of magnetic materials was confirmed by Mössbauer spectra. Powder X-ray diffraction data indicated that the structure of Fe-SBA-15 retained the host SBA-15 structure. Brunauer-Emmett-Teller analysis revealed a decrease in surface area and pore size, indicating Fe-SBA-15 coating on the inner surfaces. Scanning electron micrographs confirmed the decrease in size for modified SBA-15 particles. From scanning electron micrographs, it was found that the size of the modified SBA-15 particles decreased. Transmission electron micrographs also confirmed that modified SBA-15 retained the structure of the parent SBA-15 silica. Fe-SBA-15 exhibited strong magnetic properties, with a magnetization value of 8.8 emu g−1. The iron content in Fe-SBA-15 was determined by atom adsorption spectroscopy. Fe-SBA-15 was successfully used for the magnetic separation of three aromatic compounds in water. Our results suggest wide applicability of Fe-SBA-15 magnetic materials for the rapid and efficient separation of various compounds

The Drosophila caspase Ice is important for many apoptotic cell deaths and for spermatid individualization, a nonapoptotic process

Caspase family proteases play important roles in the regulation of apoptotic cell death. Initiator caspases are activated in response to death stimuli, and they transduce and amplify these signals by cleaving and thereby activating effector caspases. In Drosophila, the initiator caspase Nc (previously Dronc) cleaves and activates two short-prodomain caspases, Dcp-1 and Ice (previously Drice), suggesting these as candidate effectors of Nc killing activity. dcp-1-null mutants are healthy and possess few defects in normally occurring cell death. To explore roles for Ice in cell death, we generated and characterized an Ice null mutant. Animals lacking Ice show a number of defects in cell death, including those that occur during embryonic development, as well as during formation of adult eyes, arista and wings. Ice mutants exhibit subtle defects in the destruction of larval tissues, and do not prevent destruction of salivary glands during metamorphosis. Cells from Ice animals are also markedly resistant to several stresses, including X-irradiation and inhibition of protein synthesis. Mutations in Ice also suppress cell death that is induced by expression of Rpr, Wrinkled (previously Hid) and Grim. These observations demonstrate that Ice plays an important non-redundant role as a cell death effector. Finally, we demonstrate that Ice participates in, but is not absolutely required for, the non-apoptotic process of spermatid differentiation

Preparation and Characterization of an Amphipathic Magnetic Nanosphere

The amphipathic magnetic nanospheres were synthesized using C(8) and polyethylene glycol as ligands. Their morphology, structure, and composition were characterized by transmission electron microscope, Fourier transform infrared, and elementary analysis. The prepared materials presented uniform sphere with size distribution about 200 nm. The magnetic characteristics of magnetic nanomaterials were measured by vibrating sample magnetometer. The target products had a saturation magnetization value of 50 emu g(−1) and superparamagnetism. The adsorption capability was also studied by static tests, and the material was applied to enrich benzenesulfonamide from calf serum. The results exhibited that the C(8)-PEG phase owned better adsorption capability, biocompatible property, and dispersivity in aqueous samples

High frequency volatility co-movements in cryptocurrency markets

Through the application of Diagonal BEKK and Asymmetric Diagonal BEKK methodologies to intra-day data for eight cryptocurrencies, this paper investigates not only conditional volatility dynamics of major cryptocurrencies, but also their volatility co-movements. We first provide evidence that all conditional variances are significantly affected by both previous squared errors and past conditional volatility. It is also shown that both methodologies indicate that cryptocurrency investors pay the most attention to news relating to Neo and the least attention to news relating to Dash, while shocks in OmiseGo persist the least and shocks in Bitcoin persist the most, although all of the considered cryptocurrencies possess high levels of persistence of volatility over time. We also demonstrate that the conditional covariances are significantly affected by both cross-products of past error terms and past conditional covariances, suggesting strong interdependencies between cryptocurrencies. It is also demonstrated that the Asymmetric Diagonal BEKK model is a superior choice of methodology, with our results suggesting significant asymmetric effects of positive and negative shocks in the conditional volatility of the price returns of all of our investigated cryptocurrencies, while the conditional covariances capture asymmetric effects of good and bad news accordingly. Finally, it is shown that time-varying conditional correlations exist, with our selected cryptocurrencies being strongly positively correlated, further highlighting interdependencies within cryptocurrency markets

Alteration and clinical potential in gut microbiota in patients with cerebral small vessel disease

BackgroundCerebral small vessel disease (CSVD) is a cluster of microvascular disorders with unclear pathological mechanisms. The microbiota-gut-brain axis is an essential regulatory mechanism between gut microbes and their host. Therefore, the compositional and functional gut microbiota alterations lead to cerebrovascular disease pathogenesis. The current study aims to determine the alteration and clinical value of the gut microbiota in CSVD patients.MethodsSixty-four CSVD patients and 18 matched healthy controls (HCs) were included in our study. All the participants underwent neuropsychological tests, and the multi-modal magnetic resonance imaging depicted the changes in brain structure and function. Plasma samples were collected, and the fecal samples were analyzed with 16S rRNA gene sequencing.ResultsBased on the alpha diversity analysis, the CSVD group had significantly decreased Shannon and enhanced Simpson compared to the HC group. At the genus level, there was a significant increase in the relative abundances of Parasutterella, Anaeroglobus, Megasphaera, Akkermansia, Collinsella, and Veillonella in the CSVD group. Moreover, these genera with significant differences in CSVD patients revealed significant correlations with cognitive assessments, plasma levels of the blood-brain barrier-/inflammation-related indexes, and structural/functional magnetic resonance imaging changes. Functional prediction demonstrated that lipoic acid metabolism was significantly higher in CSVD patients than HCs. Additionally, a composite biomarker depending on six gut microbiota at the genus level displayed an area under the curve of 0.834 to distinguish CSVD patients from HCs using the least absolute shrinkage and selection operator (LASSO) algorithm.ConclusionThe evident changes in gut microbiota composition in CSVD patients were correlated with clinical features and pathological changes of CSVD. Combining these gut microbiota using the LASSO algorithm helped identify CSVD accurately