Preparation, Characterization and Antibacterial Properties of Silver-Chitosan Nanocomposites Using Different Molecular Weight Grades of Chitosan

Purpose: To study the effect of chitosan molecular weight on the physicochemical and antibacterial properties of silver-chitosan nanoparticles.Methods: A series of silver-chitosan nanoparticles of different sizes were produced using various molecular weight (MW) grades of chitosan by an aqueous chemical reduction method. The nanoparticles were characterized by ultraviolet-visible absorption spectroscopy (UV-Vis), scanningelectron microscopy (SEM), differential scanning calorimetry (DSC), dynamic light scattering (DLS) and laser Doppler electrophoresis (LDE). The antibacterial properties of the nanoparticles were also evaluated by agar diffusion method.Results: The size of the silver-chitosan nanoparticles, ranging from 21.9 to 175.3 nm, was influenced by chitosan MW as well as by other process conditions. Although, the nanoparticles were not stable in liquid form, they however showed good stability in the solid state due to their low zeta potential. SEM images indicate that the nanoparticles were spherical. The antibacterial activity of the nanoparticles against Staphylococcus aureus increased with decrease in particle size owing to increase in surfacearea. The smallest particle size (21.9 nm) was obtained by using high chitosan MW at 4 °C and a stirring speed of 800 rpm.Conclusion: Chitosan is an effective agent for the preparation of silver nanoparticles. The size of the nanoparticles can be modulated by varying both chitosan MW and process conditions such as temperature and stirring speed

Deletion of the Mitochondrial Superoxide Dismutase sod-2 Extends Lifespan in Caenorhabditis elegans

The oxidative stress theory of aging postulates that aging results from the accumulation of molecular damage caused by reactive oxygen species (ROS) generated during normal metabolism. Superoxide dismutases (SODs) counteract this process by detoxifying superoxide. It has previously been shown that elimination of either cytoplasmic or mitochondrial SOD in yeast, flies, and mice results in decreased lifespan. In this experiment, we examine the effect of eliminating each of the five individual sod genes present in Caenorhabditis elegans. In contrast to what is observed in other model organisms, none of the sod deletion mutants shows decreased lifespan compared to wild-type worms, despite a clear increase in sensitivity to paraquat- and juglone-induced oxidative stress. In fact, even mutants lacking combinations of two or three sod genes survive at least as long as wild-type worms. Examination of gene expression in these mutants reveals mild compensatory up-regulation of other sod genes. Interestingly, we find that sod-2 mutants are long-lived despite a significant increase in oxidatively damaged proteins. Testing the effect of sod-2 deletion on known pathways of lifespan extension reveals a clear interaction with genes that affect mitochondrial function: sod-2 deletion markedly increases lifespan in clk-1 worms while clearly decreasing the lifespan of isp-1 worms. Combined with the mitochondrial localization of SOD-2 and the fact that sod-2 mutant worms exhibit phenotypes that are characteristic of long-lived mitochondrial mutants—including slow development, low brood size, and slow defecation—this suggests that deletion of sod-2 extends lifespan through a similar mechanism. This conclusion is supported by our demonstration of decreased oxygen consumption in sod-2 mutant worms. Overall, we show that increased oxidative stress caused by deletion of sod genes does not result in decreased lifespan in C. elegans and that deletion of sod-2 extends worm lifespan by altering mitochondrial function

Genome-Wide Association Analysis of Oxidative Stress Resistance in Drosophila melanogaster

Background: Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress. Methods and Findings: We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genomewide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs) associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67–79 % and 56–66 % of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis. Conclusions: We identified novel candidate genes associated with variation in resistance to oxidative stress that hav

Quantitative and Molecular Genetic Analyses of Mutations Increasing Drosophila Life Span

Understanding the genetic and environmental factors that affect variation in life span and senescence is of major interest for human health and evolutionary biology. Multiple mechanisms affect longevity, many of which are conserved across species, but the genetic networks underlying each mechanism and cross-talk between networks are unknown. We report the results of a screen for mutations affecting Drosophila life span. One third of the 1,332 homozygous P–element insertion lines assessed had quantitative effects on life span; mutations reducing life span were twice as common as mutations increasing life span. We confirmed 58 mutations with increased longevity, only one of which is in a gene previously associated with life span. The effects of the mutations increasing life span were highly sex-specific, with a trend towards opposite effects in males and females. Mutations in the same gene were associated with both increased and decreased life span, depending on the location and orientation of the P–element insertion, and genetic background. We observed substantial—and sex-specific—epistasis among a sample of ten mutations with increased life span. All mutations increasing life span had at least one deleterious pleiotropic effect on stress resistance or general health, with different patterns of pleiotropy for males and females. Whole-genome transcript profiles of seven of the mutant lines and the wild type revealed 4,488 differentially expressed transcripts, 553 of which were common to four or more of the mutant lines, which include genes previously associated with life span and novel genes implicated by this study. Therefore longevity has a large mutational target size; genes affecting life span have variable allelic effects; alleles affecting life span exhibit antagonistic pleiotropy and form epistatic networks; and sex-specific mutational effects are ubiquitous. Comparison of transcript profiles of long-lived mutations and the control line reveals a transcriptional signature of increased life span

Role of Nrf2 Dysfunction in Uremia-Associated Intestinal Inflammation and Epithelial Barrier Disruption

Aims: To study the expression profile of inflammatory and tight junction proteins in the colon from CKD rats compared to healthy controls, and demonstrate the role of Nrf2 (transcription factor nuclear factor erythroid 2-related factor 2) using a potent Nrf2 activator

Preparation, Characterization and Antibacterial Properties of Silver-Chitosan Nanocomposites Using Different Molecular Weight Grades of Chitosan

Purpose: To study the effect of chitosan molecular weight on the physicochemical and antibacterial properties of silver-chitosan nanoparticles. Methods: A series of silver-chitosan nanoparticles of different sizes were produced using various molecular weight (MW) grades of chitosan by an aqueous chemical reduction method. The nanoparticles were characterized by ultraviolet-visible absorption spectroscopy (UV-Vis), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), dynamic light scattering (DLS) and laser Doppler electrophoresis (LDE). The antibacterial properties of the nanoparticles were also evaluated by agar diffusion method. Results: The size of the silver-chitosan nanoparticles, ranging from 21.9 to 175.3 nm, was influenced by chitosan MW as well as by other process conditions. Although, the nanoparticles were not stable in liquid form, they however showed good stability in the solid state due to their low zeta potential. SEM images indicate that the nanoparticles were spherical. The antibacterial activity of the nanoparticles against Staphylococcus aureus increased with decrease in particle size owing to increase in surface area. The smallest particle size (21.9 nm) was obtained by using high chitosan MW at 4 °C and a stirring speed of 800 rpm. Conclusion: Chitosan is an effective agent for the preparation of silver nanoparticles. The size of the nanoparticles can be modulated by varying both chitosan MW and process conditions such as temperature and stirring speed

Idiotypic vaccination with a murine anti-dsDNA antibody: phase I study in patients with nonactive systemic lupus erythematosus with nephritis

OBJECTIVE: To determine the safety and immunogenicity of an idiotypic anti-dsDNA vaccine in patients with nonactive systemic lupus erythematosus (SLE) and stable lupus nephritis. METHODS: Patients with SLE with a history of nephritis were randomized for vaccination with the murine anti-dsDNA monoclonal antibody (Mab) 3E10 in a dose ranging, double blind, placebo controlled study (phase I). RESULTS: Of the 9 patients injected with Mab 3E10, 5 showed a human anti-mouse antibody (HAMA) response, in large part antiidiotypic, which developed within the first 3 months in 3 strong HAMA responders, and more than one year after immunization in an initially weak HAMA responder. All but one nonresponder were receiving low dose prednisone. No adverse events, in particular no evidence of lupus flares, and no untoward laboratory findings were reported over a followup of 2 years. CONCLUSION: In patients with stable lupus nephritis, immunization with Mab 3E10 appears safe and can generate a significant antiidiotypic response. Idiotypic vaccination may be an approach to specific immunotherapy of autoimmune lupus nephritis