Involvement of microRNA families in cancer

Collecting representative sets of cancer microRNAs (miRs) from the literature we show that their corresponding families are enriched in sets of highly interacting miR families. Targeting cancer genes on a statistically significant level, such cancer miR families strongly intervene with signaling pathways that harbor numerous cancer genes. Clustering miR family-specific profiles of pathway intervention, we found that different miR families share similar interaction patterns. Resembling corresponding patterns of cancer miRs families, such interaction patterns may indicate a miR family’s potential role in cancer. As we find that the number of targeted cancer genes is a naïve proxy for a cancer miR family, we design a simple method to predict candidate miR families based on gene-specific interaction profiles. Assessing the impact of miR families to distinguish between (non-)cancer genes, we predict a set of 84 potential candidate families, including 75% of initially collected cancer miR families. Further confirming their relevance, predicted cancer miR families are significantly indicated in increasing, non-random numbers of tumor types.     

Effects of garlic extract consumption on blood lipid and oxidant/antioxidant parameters in humans with high blood cholesterol

Effects of garlic extract supplementation on blood lipid profile and oxidant/antioxidant status were investigated in volunteer subjects with high blood cholesterol. A total of 23 volunteer subjects with high blood cholesterol (>5.98 mmol/L) participated in the study. Of them, 13 patients were evaluated as a hypertensive group and the others a normotensive group. Before (first sample) and after (second sample) garlic extract consumption for 4 months, routine blood analyses including lipid parameters and liver and kidney function tests were performed. Additionally, blood oxidant (malondialdehyde [MDA], oxidation resistance [OR]), and antioxidant (antioxidant potential [AOP], nonenzymatic superoxide radical scavenger activity [NSSA]) parameters were measured. Serum total cholesterol, low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterols, and triglyceride levels were found to be significantly lowered, but HDL high-density lipoprotein cholesterol level increased after the extract use. The total:HDL cholesterol ratio was also found to be significantly decreased after the extract use. There were no meaningful differences with regard to other routine biochemical parameters. Additionally, blood AOP, OR, and NSSA values were found increased and MDA level decreased in the second samples relative to the first ones. Systolic and diastolic blood pressure values were also found to be significantly lowered after extract supplementation in the hypertensive group, but no similar changes were observed in the normotensive group. We conclude that garlic extract supplementation improves blood lipid profile, strengthens blood antioxidant potential, and causes significant reductions in systolic and diastolic blood pressures. It also leads to a decrease in the level of oxidation product (MDA) in the blood samples, which demonstrates reduced oxidation reactions in the body.     

G-Cimp Status Prediction Of Glioblastoma Samples Using mRNA Expression Data

Glioblastoma Multiforme (GBM) is a tumor with high mortality and no known cure. The dramatic molecular and clinical heterogeneity seen in this tumor has led to attempts to define genetically similar subgroups of GBM with the hope of developing tumor specific therapies targeted to the unique biology within each of these subgroups. Recently, a subset of relatively favorable prognosis GBMs has been identified. These glioma CpG island methylator phenotype, or G-CIMP tumors, have distinct genomic copy number aberrations, DNA methylation patterns, and (mRNA) expression profiles compared to other GBMs. While the standard method for identifying G-CIMP tumors is based on genome-wide DNA methylation data, such data is often not available compared to the more widely available gene expression data. In this study, we have developed and evaluated a method to predict the G-CIMP status of GBM samples based solely on gene expression data.     

Preparation and <Emphasis Type="Italic">In Vitro</Emphasis>/<Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Microparticle Formulations Containing Meloxicam

In this study, we have formulated chitosan-coated sodium alginate microparticles containing meloxicam (MLX) and aimed to investigate the correlation between in vitro release and in vivo absorbed percentages of meloxicam. The microparticle formulations were prepared by orifice ionic gelation method with two different sodium alginate concentrations, as 1% and 2% (w/v), in order to provide different release rates. Additionally, an oral solution containing 15 mg of meloxicam was administered as the reference solution for evaluation of in vitro/in vivo correlation (ivivc). Following in vitro characterization, plasma levels of MLX and pharmacokinetic parameters [elimination half-life (t _1/2), maximum plasma concentration (C _max), time for C _max (t _max)] after oral administration to New Zealand rabbits were determined. Area under plasma concentration–time curve (AUC_0–∞) was calculated by using trapezoidal method. A linear regression was investigated between released% (in vitro) and absorbed% (in vivo) with a model-independent deconvolution approach. As a result, increase in sodium alginate content lengthened in vitro release time and in vivo t _max value. In addition, for ivivc, linear regression equations with r ² values of 0.8563 and 0.9402 were obtained for microparticles containing 1% and 2% (w/v) sodium alginate, respectively. Lower prediction error for 2% sodium alginate formulations (7.419 ± 4.068) compared to 1% sodium alginate formulations (9.458 ± 5.106) indicated a more precise ivivc for 2% sodium alginate formulation.     

Superoxide dismutase–mimicking activities of dinuclear Cu(II) complexes with ligands containing a tetrathioether-tetraamino moiety

The superoxide scavenging activities of copper(II) complexes with the ligands, 6,6′-methylene-bis(5′-amino-3′,4′-benzo-2′-thiapentyl)-1,11-diamino-2,3:9,10-dibenzo-4,8-dithiaundecane (H₄L), and 6,6′-bis(5′-amino-3′,4′-benzo-2′-thiapentyl)-1,11-diamino-2,3:9,10-dibenzo-4,8-dithiaundecane (H₄L′), were investigated by xanthine–xanthine oxidase (X/XO) assays using nitroblue tetrazolium (NBT) as indicator molecule, and the results were compared with respect to the particular type of anion (ClO·4, Cl^·, NO·3) on the apical site of the copper(II) complexes. All of the complexes inhibited the reduction of NBT by superoxide radicals, with the [Cu₂(L′)](ClO₄)₂ complex exhibiting the highest scavenging activity against superoxide radicals among the complexes examined. The catalytic efficiency of the complexes for dismutation of superoxide radicals depends on the particular anion liganded to Cu(II) ion in the complexes, and the order of potency was observed to be ClO₄ > Cl > NO·3 in phosphate buffer at pH 7.40. The Cu(II)-H₄L′ complexes had the lowest IC₅₀ and catalytic rate constant values indicating that the distorted geometry of the Cu(II)-H₄L′ complexes influence their catalytic activities for dismutation of superoxide radicals more efficiently. The difference in the activities of the complexes toward superoxide radicals can also be attributed to the nature of the anions on the apical site of the copper(II) complexes and the superoxide dismutase-like activity. © 1997 John Wiley & Sons, Inc. J Biochem Toxicol 12: 53–59, 1998     

Mechanism of K+/Na+ selectivity in potassium channels from the perspective of the non-selective bacterial channel NaK

Studies of the non-selective NaK channel as a model system provided detailed structural and functional insights into different factors that modulate selective ion conductance. The combination of structural and functional studies of WT- and mutant forms of NaK channel show that apparent conservation of the multiple binding sites in the canonical selectivity filter of K-channel is essential component of the observed robust Na (+) discrimination.