Single Plant Derived Nanotechnology for Synergistic Antibacterial Therapies.

Multiple new approaches to tackle multidrug resistant infections are urgently needed and under evaluation. One nanotechnology-based approach to delivering new relevant therapeutics involves silicon accumulator plants serving as a viable silicon source in green routes for the fabrication of the nanoscale drug delivery carrier porous silicon (pSi). If the selected plant leaf components contain medicinally-active species as well, then a single substance can provide not only the nanoscale high surface area drug delivery carrier, but the drug itself.

Endogenous reactive oxygen species cause astrocyte defects and neuronal dysfunctions in the hippocampus: a new model for aging brain.

The etiology of astrocyte dysfunction is not well understood even though neuronal defects have been extensively studied in a variety of neuronal degenerative diseases. Astrocyte defects could be triggered by the oxidative stress that occurs during physiological aging. Here, we provide evidence that intracellular or mitochondrial reactive oxygen species (ROS) at physiological levels can cause hippocampal (neuronal) dysfunctions.

Infertility and recurrent miscarriage with complex II deficiency-dependent mitochondrial oxidative stress in animal models.

Oxidative stress is associated with some forms of both male and female infertility. However, there is insufficient knowledge of the influence of oxidative stress on the maintenance of a viable pregnancy, including pregnancy complications and fetal development. There are a number of animal models for understanding age-dependent decrease of reproductive ability and diabetic embryopathy, especially abnormal spermatogenesis, oogenesis and embryogenesis with mitochondrial dysfunctions.

Ethyl methanesulfonate induces mutations in Caenorhabditis elegans embryos at a high frequency.

Mutagenesis protocols typically call for exposure of late-stage larvae or adults to a mutagen with the intention of inducing mutations in a robust germ line. Instead, ca. 16,000 CB665 [unc-58(e665)] one- to four-cell embryos of the nematode Caenorhabditis elegans were hand selected and exposed to ethyl methanesulfonate (EMS) for 50min.

Efficient marker-free recovery of custom genetic modifications with CRISPR/Cas9 in Caenorhabditis elegans.

Facilitated by recent advances using CRISPR/Cas9, genome editing technologies now permit custom genetic modifications in a wide variety of organisms. Ideally, modified animals could be both efficiently made and easily identified with minimal initial screening and without introducing exogenous sequence at the locus of interest or marker mutations elsewhere. To this end, we describe a coconversion strategy, using CRISPR/Cas9 in which screening for a dominant phenotypic oligonucleotide-templated conversion event at one locus can be used to enrich for custom modifications at another unlinked locus.

Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion.

Historical data in the 1950s suggests that 7%, 11%, 33%, and 87% of couples were infertile by ages 30, 35, 40 and 45, respectively. Up to 22.3% of infertile couples have unexplained infertility.

Model animals for the study of oxidative stress from complex II.

Mitochondria play a role of energy production and produce intracellular reactive oxygen species (ROS), especially superoxide anion (O2(-)) as a byproduct of energy metabolism at the same time. O2(-) is converted from oxygen and is overproduced by excessive electron leakage from the mitochondrial respiratory chain. It is well known that mitochondrial complexes I and III in the electron transport system are the major endogenous ROS sources.

Mitochondrial superoxide anion overproduction in Tet-mev-1 transgenic mice accelerates age-dependent corneal cell dysfunctions.

Purpose: The Tet-mev-1 mouse expressing a mitochondrial complex-II mutated SDHC(V69E) gene controlled by a tetracycline (Tet)-On/Off system can overproduce O(2)(·-) and is a versatile whole-animal model for studying mitochondrial oxidative stress. Here we report a series of age-dependent variations in corneal epithelium, endothelium, and parenchymal cells of the Tet-mev-1 mice relative to wild-type C57BL/6j mice.

Methods: Measurements of (1) mitochondrial electron transport enzyme activities; (2) O(2)(·-) production; (3) carbonylated protein, and 8-hydroxydeoxyguanosine (8-OHdG) levels as markers of oxidative stress; (4) pathologic analyses under optical and electron microscopy; (5) hematoxylin-eosin or toluidine-blue staining; and (6) immunohistochemistry with an anti-β-catenin antibody were performed in the eye, especially the cornea.

A mutation in a mitochondrial dehydrogenase/reductase gene causes an increased sensitivity to oxidative stress and mitochondrial defects in the nematode Caenorhabditis elegans.

rad-8 is an interesting mutant that shows increased sensitivities to UV radiation and reactive oxygen species in the nematode Caenorhabditis elegans. In this study, we have characterized rad-8 and have found that rad-8 showed several phenotypes of mitochondrial dysfunction such as a decreased activity of the respiratory chain, increased generation of superoxide anions, increased oxidative damage, increased apoptosis, and abnormal mitochondrial structure. Our genetic analysis has also indicated that rad-8 has a causative mutation in the F56H1.

Mitochondrial superoxide anion (O(2)(-)) inducible "mev-1" animal models for aging research.

Most intracellular reactive oxygen species (ROS), especially superoxide anion (O(2)(-)) that is converted from oxygen, are overproduced by excessive electron leakage from the mitochondrial respiratory chain. Intracellular oxidative stress that damages cellular components can contribute to lifestyle-related diseases such as diabetes and arteriosclerosis, and age-related diseases such as cancer and neuronal degenerative diseases. We have previously demonstrated that the excessive mitochondrial O(2)(-) production caused by SDHC mutations (G71E in C.

Sustained antibacterial activity from triclosan-loaded nanostructured mesoporous silicon.

In this work, nanostructured particles of porous silicon are demonstrated to act as an effective carrier for the sustained delivery of antibacterial agents with an enhanced inhibitory activity. Methods are described for the incorporation of significant amounts of the established antibacterial compound triclosan (Irgasan) into mesoporous silicon of varying porosities. Such materials were characterized by a combination of scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD), thermal gravimetric analysis (TGA), and antimicrobial assays.

Repeated temperature fluctuation extends the life span of Caenorhabditis elegans in a daf-16-dependent fashion.

Thermocyclers were utilized to regularly shift nematodes between 12 degrees C and 25 degrees C throughout their life spans. When wild-type worms (N2) were "thermocycled" between 12 degrees C and 25 degrees C at 10-min intervals they lived almost as long as those that were incubated constantly at 12 degrees C. Shifting at 1-min or 1-h intervals lessened this effect.

Chromosome dosage as a life span determinant in Caenorhabiditis elegans.

Caenorhabiditis elegans males live longer than hermaphrodites when cultured individually. Since hermaphrodites contain a pair of X chromosomes (XX) and males are XO (there is no Y chromosome in C. elegans), we questioned whether chromosomal differences per se might impact life span.

Complex II inactivation is lethal in the nematode Caenorhabditis elegans.

RNA-mediated interference (RNAi) was employed to systematically inactivate the four subunits of complex II in the mitochondrial electron transport chain. Embryonic lethality was the predominant result of inactivating three subunits (ceSDHB, ceSDHC, and ceSDHD) when using the soaking method to inactivate RNA. The feeding method was employed to deliver dsRNA from the fourth subunit (ceSDHA) to wild-type, mev-1 (mutated in ceSDHC of complex II), and gas-1 animals (mutated in a complex I gene).

Mitochondrial oxidative stress can lead to nuclear hypermutability.

Reactive oxygen species (ROS) are generated in mitochondria and are thought to be important in aging, carcinogenesis, and the development of other pathologies. We now provide direct experimental evidence linking mitochondrial ROS generation to the induction of nuclear DNA damage and subsequent mutagenesis of a chromosomal gene. Specifically, we demonstrate that the mev-1 mutant of Caenorhabditis elegans has elevated levels of oxidative damage in its chromosomal DNA.

Relationship Between Catalase and Life Span in Recombinant Inbred Strains of Caenorhabditis elegans.

Johnson and Wood constructed recombinant inbred strains of Caenorhabditis elegans with life spans ranging from 10 to 31 days. Using these strains, we have demonstrated previously that hyperoxia and methyl viologen inhibited development at rates inversely correlated with life span. The growth rates of the short-lived recombinant inbred strains were more profoundly inhibited by oxidative stress than were those of the long-lived strains.