A study of scarless wound healing through programmed inflammation, proliferation and maturation using a redox balancing nanogel.

In the study, we have shown the efficacy of an indigenously developed redox balancing chitosan gel with impregnated citrate capped Mn3O4 nanoparticles (nanogel). Application of the nanogel on a wound of preclinical mice model shows role of various signaling molecules and growth factors, and involvement of reactive oxygen species (ROS) at every stage, namely hemostasis, inflammation, and proliferation leading to complete maturation for the scarless wound healing. While in vitro characterization of nanogel using SEM, EDAX, and optical spectroscopy reveals pH regulated redox buffering capacity, in vivo preclinical studies on Swiss albino involving IL-12, IFN-γ, and α-SMA signaling molecules and detailed histopathological investigation and angiogenesis on every stage elucidate role of redox buffering for the complete wound healing process.

Redox Buffering Effects in Potentiometric Detection of DNA Using Thiol-Modified Gold Electrodes.

Label-free potentiometric detection of DNA molecules using a field-effect transistor (FET) with a gold gate offers an electrical sensing platform for rapid, straightforward, and inexpensive analyses of nucleic acid samples. To induce DNA hybridization on the FET sensor surface to enable potentiometric detection, probe DNA that is complementary to the target DNA has to be immobilized on the FET gate surface. A common method for probe DNA functionalization is based on thiol-gold chemistry, immobilizing thiol-modified probe DNA on a gold gate with thiol-gold bonds. A self-assembled monolayer (SAM), based on the same thiol-gold chemistry, is also needed to passivate the rest of the gold gate surface to prevent non-specific adsorption and to enable favorable steric configuration of the probe DNA. Herein, the applicability of such FET-based potentiometric DNA sensing was carefully investigated, using a silicon nanoribbon FET with a gold-sensing gate modified with thiol-gold chemistry. We discover that the potential of the gold-sensing electrode is determined by the mixed potential of the gold-thiol and gold-oxygen redox interactions. This mixed potential gives rise to a redox buffer effect which buffers the change in the surface charge induced by the DNA hybridization, thus suppressing the potentiometric signal. Analogous redox buffer effects may also be present for other types of potentiometric detections of biomarkers based on thiol-gold chemistry.

Redox Buffering Capacity of Nanomaterials as an Index of ROS-Based Therapeutics and Toxicity: A Preclinical Animal Study.

Precise control of intracellular redox status, i.e., maintenance of the physiological level of reactive oxygen species (ROS) for mediating normal cellular functions (oxidative eustress) while evading the excess ROS stress (distress), is central to the concept of redox medicine. In this regard, engineered nanoparticles with unique ROS generation, transition, and depletion functions have the potential to be the choice of redox therapeutics. However, it is always challenging to estimate whether ROS-induced intracellular events are beneficial or deleterious to the cell. Here, we propose the concept of redox buffering capacity as a therapeutic index of engineered nanomaterials. As a steady redox state is maintained for normal functioning cells, we hypothesize that the ability of a nanomaterial to preserve this homeostatic condition will dictate its therapeutic efficacy. Additionally, the redox buffering capacity is expected to provide information about the nanoparticle toxicity. Here, using citrate-functionalized trimanganese tetroxide nanoparticles (C-Mn3O4 NPs) as a model nanosystem, we explored its redox buffering capacity in erythrocytes. Furthermore, we went on to study the chronic toxic effect (if any) of this nanomaterial in the animal model to co-relate with the experimentally estimated redox buffering capacity. This study could function as a framework for assessing the capability of a nanomaterial as redox medicine (whether maintains eustress or damages by creating distress), thus orienting its application and safety for clinical use.

An investigation into the impact of deleting one copy of the glutaredoxin-2 gene on diet-induced weight gain and the bioenergetics of muscle mitochondria in female mice fed a high fat diet.

Our group recently documented that male mice containing a deletion for one copy of the glutaredoxin-2 (Grx2) gene were completely protected from developing diet-induced obesity (DIO). Objectives: Here, we conducted a similar investigation but with female littermates. Results: In comparison to our recent publication using male mice, exposure of WT and GRX2+/- female mice to a HFD from 3-to-10 weeks of age did not induce any changes in body mass, circulating blood glucose, food intake, hepatic glycogen levels, or abdominal fat pad mass. Examination of the bioenergetics of muscle mitochondria revealed no changes in the rate of superoxide ( O 2 ∙ - )/hydrogen peroxide (H2O2) or O2 consumption under different states of respiration or alterations in lipid peroxidation adduct levels regardless of mouse strain or diet. Additionally, we measured the bioenergetics of mitochondria isolated from liver tissue and found that partial loss of GRX2 augmented respiration but did not alter ROS production. Discussion: Overall, our findings demonstrate there are sex differences in the protection of female GRX2+/- mice from DIO, fat accretion, intrahepatic lipid accumulation, and the bioenergetics of mitochondria from muscle and liver tissue.

Flux through mitochondrial redox circuits linked to nicotinamide nucleotide transhydrogenase generates counterbalance changes in energy expenditure.

Compensatory changes in energy expenditure occur in response to positive and negative energy balance, but the underlying mechanism remains unclear. Under low energy demand, the mitochondrial electron transport system is particularly sensitive to added energy supply (i.e. reductive stress), which exponentially increases the rate of H2O2 (JH2O2) production. H2O2 is reduced to H2O by electrons supplied by NADPH. NADP+ is reduced back to NADPH by activation of mitochondrial membrane potential-dependent nicotinamide nucleotide transhydrogenase (NNT). The coupling of reductive stress-induced JH2O2 production to NNT-linked redox buffering circuits provides a potential means of integrating energy balance with energy expenditure. To test this hypothesis, energy supply was manipulated by varying flux rate through ß-oxidation in muscle mitochondria minus/plus pharmacological or genetic inhibition of redox buffering circuits. Here we show during both non-ADP- and low-ADP-stimulated respiration that accelerating flux through ß-oxidation generates a corresponding increase in mitochondrial JH2O2 production, that the majority (∼70-80%) of H2O2 produced is reduced to H2O by electrons drawn from redox buffering circuits supplied by NADPH, and that the rate of electron flux through redox buffering circuits is directly linked to changes in oxygen consumption mediated by NNT. These findings provide evidence that redox reactions within ß-oxidation and the electron transport system serve as a barometer of substrate flux relative to demand, continuously adjusting JH2O2 production and, in turn, the rate at which energy is expended via NNT-mediated proton conductance. This variable flux through redox circuits provides a potential compensatory mechanism for fine-tuning energy expenditure to energy balance in real time.

Migration of Iron Oxide Nanoparticle through a Silica Shell by the Redox-Buffering Effect.

This study demonstrates that mineral redox buffer, an important concept in geology, can be used to manipulate the migration of nanoparticles and produce nanostructures of unexpected morphologies. Using a silica shell as a redox buffer, we show that iron oxide nanoparticles can be relocated from inside to the outer surface of the silica shell. The migration of iron oxide through silica was initiated by manipulation of the oxygen fugacity conditions at an elevated temperature. During the treatment, iron oxide was absorbed and then separated from the silica shell by the formation and then decomposition of iron silicate (Fe2SiO4). Tuning the relative dimensions of the iron oxide core and silica shell allows control of the shape of the iron oxide-silica composite structures. It is believed that the discovery of the nanoscale redox buffering effect can be extended to control the morphological configuration of other multivalent metal oxide nanocomposite structures by this particular type of template synthesis through manipulation of the chemical-transport properties of nanoscale templates.