Chelation of chromium(VI) by combining deferasirox and deferiprone in rats

The present research is aimed to characterize the potential efficiency of two chelators after chromium(VI) administration for 60 days following two doses of 15 and 30 mg/kg chromium(VI) per body weight daily to male rats. However, the hypothesis that the two chelators might be more efficient as combined therapy than as single therapy in removing chromium(VI) from rat organs was considered. In this way, two known chelators deferasirox and deferiprone were chosen and given orally as a single or combined therapy for a period of 1 week. Chromium(VI) and iron concentrations in tissues were determined by flame atomic absorption spectroscopy. The combined chelation therapy results show that deferasirox and deferiprone are able to remove chromium(VI) ions from various tissues while iron concentration returned to normal levels and symptoms also decreased.     

Effects of Static Magnetic Fields on the Antioxidant System of Almond Seeds

Russian Journal of Plant Physiology - During the evolutionary process, all living cells experience natural magnetic fields (geo-magnetic fields) as a usual part of their environment. Living...     

Natural Biased Coin Encoded in the Genome Determines Cell Strategy

Decision making at a cellular level determines different fates for isogenic cells. However, it is not yet clear how rational decisions are encoded in the genome, how they are transmitted to their offspring, and whether they evolve and become optimized throughout generations. In this paper, we use a game theoretic approach to explain how rational decisions are made in the presence of cooperators and competitors. Our results suggest the existence of an internal switch that operates as a biased coin. The biased coin is, in fact, a biochemical bistable network of interacting genes that can flip to one of its stable states in response to different environmental stimuli. We present a framework to describe how the positions of attractors in such a gene regulatory network correspond to the behavior of a rational player in a competing environment. We evaluate our model by considering lysis/lysogeny decision making of bacteriophage lambda in E. coli.     

Responses of growth and antioxidant systems in <Emphasis Type="Italic">Carthamus</Emphasis><Emphasis Type="Italic">tinctorius</Emphasis> L. under water deficit stress

An investigation was carried out to find out the extent of changes occurred in two safflower (Carthamus tinctorius L.) cultivars in response to water deficit stress. Two safflower cultivars namely IL.111 and Isfahan were used for the study. Thirty days after sowing, plants were grown under soil moisture corresponding to 100, 85, 70 and 55% field capacity for next 30 days. Water deficit treatments significantly decreased the shoot length, shoot dry matter, root dry matter, relative growth rate, leaf relative water content (LRWC) and leaf water potential (Ψ_W), whereas root length, root-to-shoot ratio, lipid peroxidation and antioxidant compounds such as ascorbic acid (AA), α-tocopherol (α-Toc) and reduced glutathione (GSH) and superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), and peroxidase (POX, EC 1.11.1.7) activities were increased. Water deficit stressed plants maintained higher levels of compounds and scavenging enzymes. Significant differences were observed between cultivars and irrigation levels treatments. The cv. IL.111 could be considered more tolerant to water stress than cv. Isfahan, registering greater biomass, LRWC and leaf water potential (Ψ_W), associated with high antioxidant activity.     

Differential effects of acetaminophen on enzymatic and non-enzymatic antioxidant factors and plasma total antioxidant capacity in developing and adult rats

Recently we reported that ferric reducing ability of plasma (FRAP) assay, as an index of total antioxidant activity, increases in growing rats in response to high dose of vitamin K. In this study, it was found that acetaminophen (APAP) can cause elevation in FRAP in suckling and adult rats. This study was initiated to assess the contribution of individual antioxidant factors on elevation in FRAP. A surge in FRAP, 1 h after high dose APAP (250 or 450 mg/kg BW) administration was recorded in both young as well as adults. Whereas, low dose drug (25 mg/kg) failed to alter FRAP in both the age groups. Time-course studies show that drug-dependent elevation in FRAP begin rapidly, reaching a maximum at 1 h (> 500%). Increased FRAP was associated with a marked increase (∼14-fold) in plasma bilirubin, 6 h after drug administration at 450 mg/kg only in suckling rats. Similarly, APAP-related increase in superoxide dismutase activity in erythrocytes was limited to young rats of both the age groups. Other factors measured during this period viz., plasma uric acid, bilirubin and total protein together with catalase activity of erythrocytes remained unchanged in treated rats. Under these circumstances, APAP-related depletion in liver glutathione was almost similar in both the age groups. During a 12 h study, the concentration of lipid peroxidation products, in liver of treated groups remained within the levels of respective controls. The endpoint hepatotoxic effects of APAP was almost similar in both the age groups, suggesting that like adults, immature rats can cope with toxic effects of APAP owing to their drug-dependent induction in certain antioxidant factors.     

CHOPER Filters Enable Rare Mutation Detection in Complex Mutagenesis Populations by Next-Generation Sequencing

Next-generation sequencing (NGS) has revolutionized genetics and enabled the accurate identification of many genetic variants across many genomes. However, detection of biologically important low-frequency variants within genetically heterogeneous populations remains challenging, because they are difficult to distinguish from intrinsic NGS sequencing error rates. Approaches to overcome these limitations are essential to detect rare mutations in large cohorts, virus or microbial populations, mitochondria heteroplasmy, and other heterogeneous mixtures such as tumors. Modifications in library preparation can overcome some of these limitations, but are experimentally challenging and restricted to skilled biologists. This paper describes a novel quality filtering and base pruning pipeline, called Complex Heterogeneous Overlapped Paired-End Reads (CHOPER), designed to detect sequence variants in a complex population with high sequence similarity derived from All-Codon-Scanning (ACS) mutagenesis. A novel fast alignment algorithm, designed for the specified application, has O(n) time complexity. CHOPER was applied to a p53 cancer mutant reactivation study derived from ACS mutagenesis. Relative to error filtering based on Phred quality scores, CHOPER improved accuracy by about 13% while discarding only half as many bases. These results are a step toward extending the power of NGS to the analysis of genetically heterogeneous populations.     

Effect of curcumin on glioblastoma cells

Curcumin is a polyphenolic compound derived from Curcumin longa L. There are growing bodies of evidence revealing the antitumor effect of curcumin in different tumors; although the molecular mechanism behind this inhibition in glioblastoma multiform (GBM) still remains unclear. Here we investigated the antitumor activity of nano micelles curcumin compared with erlotinib in U-373 cells in monolayer cell cultures and spheroids models. Furthermore, we characterized affecting cell cycle perturbation, as well as apoptosis induction in GBM cells. The antiproliferative activity of nano micelles curcumin and erlotinib were assessed in monolayer and spheroid models. The influence of the cell cycle and expression levels of nuclear factor κB (NF-κB) and Wnt/β-catenin pathway was checked. Nano micelles curcumin suppressed cell growth in U-373 cells via modulation of Wnt and NF-κB pathways. Moreover, cells developed an early G2/M cell cycle arrest followed by sub-G1 apoptosis and apoptotic bodies formation posttreatment with nano micelles curcumin and erlotinib. In the core signaling pathways of GBM, nano micelles curcumin either significantly influences the NF-κB pathway by decreasing p-65 expression or significantly inhibits the Wnt/β-catenin pathway by declining cyclin D1 expression. In conclusion, we have shown that nano micelles curcumin effectively prevent proliferation, and invasion of GBM cells through perturbation of Wnt/β-catenin and NF-κB pathways, suggesting further investigations on the therapeutic application of this novel anticancer drug in in vivo models.     

Prediction of HCV load using genotype,liver biomarkers,and clinical symptoms by a mathematical model in patients with HCV infection

Hepatitis C virus (HCV) infection is a major public health problem with about 1.75 million new HCV cases and 71 million chronic HCV infections worldwide. The study aimed to evaluate clinical, serological, molecular, and liver markers to develop a mathematical predictive model for the quantification of the HCV viral load in chronic HCV infected patients. In this cross‐sectional study, blood samples were taken from 249 recently diagnosed HCV‐infected subjects and were tested for liver condition, viral genotype, and HCV RNA load. Receiver operating characteristics (ROC) curves and multiple linear regression analysis were used to predict the HCV‐RNA load. Genotype 3 followed by genotype 1 were the most prevalent genotypes in Mashhad, Northeastern Iran. The maximum levels of viral load were detected in the mixed genotype group, and the lowest levels in the undetectable genotype group. The log of the HCV viral load was significantly associated with thrombocytopenia and higher serum levels of alanine transaminase (ALT). In addition, the log HCV RNA was significantly higher in patients with arthralgia, fatigue, fever, vomiting, or dizziness. Moreover, genotype 3 was significantly associated with icterus. A ROC curve analysis revealed that the best cut‐off points for serum levels of aspartate aminotransferase (AST), ALT, and alkaline phosphatase (ALP) were >31, >34, and ≤246 IU/L, respectively. Sensitivity, specificity, and positive predictive values for AST were 87.7%, 84.36%, and 44.6%, for ALT they were 83.51%, 81.11%, and 36%, and for ALP were 72.06%, 42.81%, and 8.3%, respectively. A mathematical regression model was developed that could estimate the HCV‐RNA load. Regression model: log viral load = 7.69 ? 1.01 × G3 ? 0.7 × G1 + 0.002 × ALT ? 0.86 × fatigue.     

Genetic Diversity and Antifungal Susceptibility of <Emphasis Type="Italic">Candida parapsilosis</Emphasis> Sensu Stricto Isolated from Bloodstream Infections in Turkish Patients

Candida parapsilosis sensu stricto is an emerging cause of hospital-acquired Candida infections, predominantly in southern Europe, South America, and Asia. We investigated the genetic diversity and antifungal susceptibility profile of 170 independent C. parapsilosis sensu stricto strains obtained from patients with candidemia who were treated at the Ege University Hospital in Izmir, Turkey, between 2006 and 2014. The identity of each strain was confirmed via PCR amplification and digestion of the secondary alcohol dehydrogenase-encoding gene. The 24-h geometric mean minimum inhibitory concentrations of the antifungal agents, in increasing order, were as follows: posaconazole, 0.10 µg/mL; voriconazole, 0.21 µg/mL; caspofungin, 0.38 µg/mL; amphotericin B, 0.61 µg/mL; anidulafungin, 0.68 µg/mL; and fluconazole, 2.95 µg/mL. Microsatellite genotyping of the isolates (using fluorescently labeled primers and a panel of four different short-nucleotide repeat fragments) identified 25, 17, 17, and 8 different allelic genotypes at the CP6, B5, CP4, and CP1 locus, respectively. Posaconazole, caspofungin, and amphotericin B showed the greatest in vitro activity of the tested systemic azole, echinocandin, and polyene agents, respectively, and the observed antifungal susceptibility of the isolates was shown to be independent of their isolation source. We obtained a combined discriminatory power of 0.99 with a total of 130 genotypes for 170 isolates tested. Finally, microsatellite profiling analysis confirmed the presence of identical genotype between separate isolates, supporting that effective surveillance and infection-prevention programs are essential to limit the impact of C. parapsilosis sensu stricto on hospitalized patients’ health.