Role Of Reactive Oxygen Species Research Articles

Therapeutic Targeting of Mitochondrial Plasticity and Redox Control to Overcome Cancer Chemoresistance.

Mitochondria are subcellular organelles performing essential metabolic functions contributing to cellular bioenergetics and regulation of cell growth or death. The basic mitochondrial function in fulfilling the need for cell growth and vitality is evidenced by the conditional state whereby cancer cells with depleted mitochondrial DNA (rho zero cells) are no longer capable of forming tumors until newly recruited mitochondria are internalized into the rho zero cells. Herein lies the absolute dependency on mitochondria for tumor growth. In addition, mitochondria are key regulators of cell death (by apoptosis, necroptosis, or other forms of cell death) and are therefore important targets for anticancer therapy. Mitochondrial plasticity regulating their state of fusion or fission is also key to the chemoresistance properties of cancer cells by promoting pro-survival pathways enabling the mitochondria to mitigate against the cellular stresses and extreme conditions within the tumor microenvironment caused by chemotherapy, hypoxia, or oxidative stress. This review discusses many characteristics of mitochondria, the processes and pathways controlling the dynamic changes occurring in the morphology of mitochondria, the roles of reactive oxygen species, and their relationship with mitochondrial fission or fusion. It also examines the relationship of redox to mitophagy when mitochondria become compromised and its effect on cancer cell survival, stemness and the changes accompanying malignant progression from primary tumors to metastatic disease. A challenging question that arises is whether the changes in mitochondrial dynamics and their regulation can provide opportunities for improving drug targeting during cancer treatment and enhancing survival outcomes.

Nonmicrobial mechanisms dominate the release of CO2 and the decomposition of organic matter during the short-term redox process in paddy soil slurry

Both biotic and abiotic mechanisms play a role in soil CO2 emission processes. However, abiotically mediated CO2 emission and the role of reactive oxygen species are still poorly understood in paddy soil. This study revealed that OH promoted CO2 emission in paddy soil slurries during short-term oxidation (4 h). OH generation was highly hinged on active Fe(II) content, and the OH contribution to CO2 efflux was 10%–33% in topsoil and 40%–77% in deep-soil slurries. Net CO2 efflux was higher in topsoil slurries, which contained more dissolved organic carbon (DOC). CO2 efflux correlated well with DOC contents, suggesting the critical role of DOC. Microbial mechanisms contributed 9%–45% to CO2 production, as estimated by γ-ray sterilization experiments in the short-term reoxidation process. Solid-aqueous separation experiments showed a significant reduction in net CO2 efflux across all soil slurries after the removal of the original aqueous phase, indicating that the water phase was the main source of CO2 emission (>50%). Besides, C emission was greatly affected by pH fluctuation in acidic soil but not in neutral/alkaline soils. Fourier transform ion cyclotron resonance mass spectrometry and excitation-emission matrix results indicated that recalcitrant and macromolecular dissolved organic matter (DOM) components were more easily removed or attacked by OH. The decrease in DOM content during the short-term reoxidation was the combined result of OH oxidation, co-precipitation, and soil organic matter release. This study emphasizes the significance of the generally overlooked nonmicrobial mechanisms in promoting CO2 emission in the global C cycle, and the critical influence of the aqueous phase on C loss in paddy environments.

Comparative toxicity assessment of individual, binary and ternary mixtures of SiO2, Fe3O4, and ZnO nanoparticles in freshwater microalgae, Scenedesmus obliquus: Exploring the role of dissolved ions

Metal oxide nanoparticles (NPs) are considered among the most prevalent engineered nanomaterials. To have a deeper understanding of the mode of action of multiple metal oxide nanoparticles in mixtures, we have used a unicellular freshwater microalga Scenedesmus obliquus as a model organism. The toxicity of silicon dioxide (SiO2), iron oxide (Fe3O4), and zinc oxide (ZnO) NPs was studied individually as well as in their binary (SiO2 + Fe3O4, Fe3O4 + ZnO, and ZnO + SiO2) and ternary (SiO2 + Fe3O4 + ZnO) combinations. The effects of metal ions from ZnO and Fe3O4 were investigated as well. The results observed from the study, showed that a significant amount of toxicity was contributed by the dissolved ions in the mixtures of the nanoparticles. Decreases in the cell viability, ROS generation, lipid peroxidation, antioxidant enzyme activity, and photosynthetic efficiency were analyzed. Among all the individual particles, ZnO NPs showed the maximum effects and increased the toxicities of the binary mixtures. The binary and ternary mixtures of the NPs clearly showed increased toxic effects in comparison with the individual entities. However, the ternary combination had lesser toxic effects than the binary combination of Fe3O4 + ZnO. The decline in cell viability and photosynthetic efficiency were strongly correlated with various oxidative stress biomarkers emphasizing the crucial role of reactive oxygen species in inducing the toxic effects. The findings from this study highlight the importance of evaluating the combinatorial effects of various metal oxide NPs as part of a comprehensive ecotoxicity assessment in freshwater microalgae.

Salinity-Induced Physiochemical Alterations to Enhance Lipid Content in Oleaginous Microalgae Scenedesmus sp. BHU1 via Two-Stage Cultivation for Biodiesel Feedstock.

In the recent past, various microalgae have been considered a renewable energy source for biofuel production, and their amount and extent can be enhanced by applying certain types of stress including salinity. Although microalgae growing under salinity stress result in a higher lipid content, they simultaneously reduce in growth and biomass output. To resolve this issue, the physiochemical changes in microalgae Scenedesmus sp. BHU1 have been assessed through two-stage cultivation. In stage-I, the maximum carbohydrate and lipid contents (39.55 and 34.10%) were found at a 0.4 M NaCl concentration, while in stage-II, the maximum carbohydrate and lipid contents (42.16 and 38.10%) were obtained in the 8-day-old culture. However, under increased salinity, Scenedesmus sp. BHU1 exhibited a decrease in photosynthetic attributes, including Chl-a, Chl-b, Fv/Fm, Y(II), Y(NPQ), NPQ, qP, qL, qN, and ETRmax but increased Y(NO) and carotenoids content. Apart from physiological attributes, osmoprotectants, stress biomarkers, and nonenzymatic antioxidants were also studied to elucidate the role of reactive oxygen species (ROS) facilitated lipid synthesis. Furthermore, elemental and mineral ion analysis of microalgal biomass was performed to evaluate the biomass quality for biofuel and cell homeostasis. Based on fluorometry analysis, we found the maximum neutral lipids in the 8-day-old grown culture at stage-II in Scenedesmus sp. BHU1. Furthermore, the use of Fourier-transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy analyses confirmed the presence of higher levels of hydrocarbons and triacylglycerides (TAGs) composed of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) in the 8-day-old culture. Therefore, Scenedesmus sp. BHU1 can be a promising microalga for potential biodiesel feedstock.

Multi-endpoint analysis of cadmium chloride-induced genotoxicity shows role for reactive oxygen species and p53 activation in DNA damage induction, cell cycle irregularities, and cell size aberrations.

Cadmium chloride (CdCl2) is a known genotoxic carcinogen, with a mechanism of action thought to partly involve the generation of reactive oxygen species (ROS). We applied here a multi-endpoint approach in vitro to explore the impact of CdCl2 on both the genome and on wider cell biology pathways relevant to cancer. Multi-endpoint approaches are believed to offer greater promise in terms of understanding the holistic effects of carcinogens in vitro. This richer understanding may help better classification of carcinogens as well as allowing detailed mechanisms of action to be identified. We found that CdCl2 caused DNA damage [micronuclei (MN)] in both TK6 and NH32 cells in a dose-dependent manner after 4 h exposure (plus 23 h recovery), with lowest observable effect levels (LOELs) for MN induction of 1 μM (TK6) and 1.6 μM (NH32). This DNA damage induction in TK6 cells was ROS dependent as pretreatment with the antioxidant N-Acetyl Cysteine (1 mM), abrogated this effect. However, 2',7'-dichlorofluorescin diacetate was not capable of detecting the ROS induced by CdCl2. The use of NH32 cells allowed an investigation of the role of p53 as they are a p53 null cell line derived from TK6. NH32 showed a 10-fold increase in MN in untreated cells and a similar dose-dependent effect after CdCl2 treatment. In TK6 cells, CdCl2 also caused activation of p53 (accumulation of total and phosphorylated p53), imposition of cell cycle checkpoints (G2/M) and intriguingly the production of smaller and more eccentric (elongated) cells. Overall, this multi-endpoint study suggests a carcinogenic mechanism of CdCl2 involving ROS generation, oxidative DNA damage and p53 activation, leading to cell cycle abnormalities and impacts of cell size and shape. This study shows how the integration of multiple cell biology endpoints studied in parallel in vitro can help mechanistic understanding of how carcinogens disrupt normal cell biology.

Comparative studies on the effect of salinity and drought stress on enzymatic antioxidant defense system of two maize (<i>Zea mays</i> l.). varieties

Soil salinization and drought are serious threat to crop productivity and predicted to increase in face of global climate change. Studies have shown that as much as the 12 billion US dollar will be lost globally each year, due to the reduction in agricultural production from drought and salt-affected areas. Maize is an economically important cereal crop affected by high salinity and drought stress, maize seedling was subjected to 50 mM, 100 mM and 150 mM NaCl and 4, 6 and 8 days to emulate high soil salinity and drought stress. Root and mature leaves were harvested after 21 days of sowing. High salinity induced oxidative stress in the root and mature leaves. The root and matured leaves showed increased malondialdehyde (MDA) and the hydrogen peroxide (H2O2) concentration at 50, 100 and 150 mM NaCl and 4, 6, and 8 days of drought strss. Activities of enzymatic antioxidants, Catylase (CAT, E .C 1.11.1.6) increase in all organs of salt treated maize seedling, while superoxide dismutase (SOD, 1.15.1.1) and peroxidase (POX, E.C. 1.11.1.7) increased specifically in mature leaves. This indicates a possible role of reactive oxygen species (ROS) in the systemic signaling from roots to leaves, allowing leaves to activate their defense mechanism for better protection against salt and drought stress.

CONCEPT OF SEED DETERIORATION: REASON, FACTORS, CHANGES DURING DETERIORATION AND PREVENTIVE MEASURES TO OVERCOME SEED DEGRADATION

Seed deterioration is when a seed loses its vigor and eventually loses viability. Seed viability is an important trait that directly influences seedling emergence and crop yield. The rate of seed deterioration varies on several factors. Our main aims were to express the methods for testing seed deterioration, factors influencing seed aging, stages of seed deterioration, changes associated with seed deterioration, Practical approaches to overcome seed deterioration, and the role of reactive oxygen species during seed aging. From this investigation, it can be concluded that high temperatures and high relative humidity can hasten the degradation of seeds. An increase in the loss of seed leachate, a drop in respiration rates and ATP production, a loss of enzyme activity, and organelle structural breakdown are often seen as changes as seeds age. Various factors can cause seed aging, but the main cause is probably oxidative damage brought on by free radicals and reactive oxygen species (ROS). Protein oxidation, lipid peroxidation, chromosomal abnormalities, and DNA damage can all be induced by ROS, which can have critical interactions with any macromolecule of biological significance. In the early stages of imbibition, some repairs may occur, and seeds will lose their viability within a short period. Seed deterioration can be retrieved through different priming and exogenous application of plant growth regulators.

Mechanisms of Cysteine‐Lysine Covalent Linkage—The Role of Reactive Oxygen Species and Competition with Disulfide Bonds**

AbstractRecently, a new naturally occurring covalent linkage was characterised, involving a cysteine and a lysine, bridged through an oxygen atom. The latter was dubbed as the NOS bond, reflecting the individual atoms involved in this uncommon bond which finds little parallel in lab chemistry. It is found to form under oxidising conditions and is reversible upon addition of reducing agents. Further studies have identified the bond in crystal structures across a variety of systems and organisms, potentially playing an important role in regulation, cellular defense and replication. Not only that, double NOS bonds have been identified and even found to be competitive in relation to the formation of disulfide bonds. This raises several questions about how this exotic bond comes to be, what are the intermediates involved in its formation and how it competes with other pathways of sulfide oxidation. With this objective in mind, we revisited our first proposed mechanism for the reaction with model electronic structure calculations, adding information about the reactivity with alternative reactive oxygen species and other potential competing products of oxidation. We present a network with more than 30 reactions which provides one of the most encompassing pictures for cysteine oxidation pathways to date.

Mechanisms of Cysteine-Lysine Covalent Linkage-The Role of Reactive Oxygen Species and Competition with Disulfide Bonds.

Recently, a new naturally occurring covalent linkage was characterised, involving a cysteine and a lysine, bridged through an oxygen atom. The latter was dubbed as the NOS bond, reflecting the individual atoms involved in this uncommon bond which finds little parallel in lab chemistry. It is found to form under oxidising conditions and is reversible upon addition of reducing agents. Further studies have identified the bond in crystal structures across a variety of systems and organisms, potentially playing an important role in regulation, cellular defense and replication. Not only that, double NOS bonds have been identified and even found to be competitive in relation to the formation of disulfide bonds. This raises several questions about how this exotic bond comes to be, what are the intermediates involved in its formation and how it competes with other pathways of sulfide oxidation. With this objective in mind, we revisited our first proposed mechanism for the reaction with model electronic structure calculations, adding information about the reactivity with alternative reactive oxygen species and other potential competing products of oxidation. We present a network with more than 30 reactions which provides one of the most encompassing pictures for cysteine oxidation pathways to date.

Role of reactive oxygen species in the toxicity of two-dimensional nanomaterials: A study on layered Ti3C2 MXenes

Two-dimensional (2D) materials, such as MXenes and graphene, are tested as catalysts, sensors, and nanomedicine, but their safety and biocompatibility are poorly understood. In this study, Ti3C2 MXenes (single-layer and multilayer) and graphene oxide are prepared to evaluate their inflammatory potential in vivo and in vitro using the read-across approach. Pulmonary exposure of the test materials in mice led to significant dose-dependent increases in several toxicity endpoints of bronchoalveolar lavage fluid. The correlation of the oxidative potential of the test materials and the toxicity endpoints shows that both the intrinsic and intracellular oxidative potentials of 2D materials are key factors for the inflammation and damage of the plasma membrane. Scanning electron microscopy and in vitro studies using the differentiated THP-1 macrophage-like cells support this finding. Furthermore, the toxicity of test items is reduced when treated with N-acetyl cysteine, a scavenger for reactive oxygen species; this finding further supports the oxidative stress paradigm proposed in this study. This oxidative stress paradigm may apply to 2D materials in general and improve the understanding the toxicity mechanism of such materials, which would facilitate the design of safer functional 2D materials.

Mechanisms involved in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox)-derived reactive oxygen species (ROS) modulation of muscle function in human and dog bladders.

Roles of redox signaling in bladder function is still under investigation. We explored the physiological role of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) in regulating bladder function in humans and dogs. Mucosa-denuded bladder smooth muscle strips obtained from 7 human organ donors and 4 normal dogs were mounted in muscle baths, and trains of electrical field stimulation (EFS) applied for 20 minutes at 90-second intervals. Subsets of strips were incubated with hydrogen peroxide (H2O2), angiotensin II (Ang II; Nox activator), apocynin (inhibitor of Noxs and ROS scavenger), or ZD7155 (specific inhibitor of angiotensin type 1 (AT1) receptor) for 20 minutes in continued EFS trains. Subsets treated with inhibitors were then treated with H2O2 or Ang II. In human and dog bladders, the ROS, H2O2 (100μM), caused contractions and enhanced EFS-induced contractions. Apocynin (100μM) attenuated EFS-induced strip contractions in both species; subsequent treatment with H2O2 restored strip activity. In human bladders, Ang II (1μM) did not enhance EFS-induced contractions yet caused direct strip contractions. In dog bladders, Ang II enhanced both EFS-induced and direct contractions. Ang II also partially restored EFS-induced contractions attenuated by prior apocynin treatment. In both species, treatment with ZD7155 (10μM) inhibited EFS-induced activity; subsequent treatment with Ang II did not restore strip activity. Collectively, these data provide evidence that ROS can modulate bladder function without exogenous stimuli. Since inflammation is associated with oxidative damage, the effects of Ang II on bladder smooth muscle function may have pathologic implications.

Co+2, Ni+2 and Cu+2 incorporated Bi2O3 nano photocatalysts: Synthesis, DFT analysis of band gap modification, adsorption and photodegradation analysis of rhodamine B and Triclopyr

This study deals with the fabrication of metal ion (M = Co+2, Ni+2, and Cu+2) doped- Bi2O3 photocatalysts by solution combustion method. All the synthesized materials were characterized and analysed with the help of XRD, FESEM, EDX, HRTEM, UVDRS, Zeta potential, PL, and LCMS techniques for the structural, morphological, surface charge, optical and degradation pathways characteristics. Synthesized compounds were used for the decontamination (adsorption and degradation) of two organic pollutants namely Rhodamine B and Triclopyr. Adsorption aspects of the pollutants were studied in terms of different isotherm, kinetic and thermodynamic models. Adsorption phenomenon was best fitted with the Freundlich (R2 = 0.992) and Langmuir isotherm (R2 = 0.999) models along with pseudo second order model of kinetics for RhB and TC, respectively. Moreover, the thermodynamic parameters indicated exothermic and endothermic adsorption (ΔH ° (−7.19 kJ/mol) for RhB) and (ΔH ° (52.335 kJ/mol) for TC), respectively. Evaluated negative values of ΔG ° indicated spontaneous adsorption with most favourable at 298 K and 318 K for both the pollutants (RhB and TC) respectively. Modification with metal ions significantly improved the removal efficiency of pure Bi2O3 photocatalyst and followed the trend Co+2/Bi2O3 > Ni+2/Bi2O3 > Cu+2/Bi2O3 > Bi2O3. DFT calculations demonstrate that amongst the doped materials, only Co+2/Bi2O3 is characterized by an indirect band gap; which exhibited efficacious photocatalytic activity. Besides, the highest degradation efficiency was obtained in the case of Co+2/Bi2O3 (2 mol %); being 99.80% for RhB in 30 min and 98.50% for TC in 60 min, respectively. The doped nanostructures lead to higher absorption of visible light and more separation of light-induced charged carriers. Effect of pH of the reaction medium and role of reactive oxygen species was also examined. Finally, a probable mechanism of charge transfer and degradation of the pollutants was also presented.

Chitosan functionalized Mn3O4 nanoparticles counteracts ulcerative colitis in mice through modulation of cellular redox state

Recent findings suggest a key role for reactive oxygen species (ROS) in the pathogenesis and progression of ulcerative colitis (UC). Several studies have also highlighted the efficacy of citrate functionalized Mn3O4 nanoparticles as redox medicine against a number of ROS-mediated disorders. Here we show that synthesized nanoparticles consisting of chitosan functionalized tri-manganese tetroxide (Mn3O4) can restore redox balance in a mouse model of UC induced by dextran sulfate sodium (DSS). Our in-vitro characterization of the developed nanoparticle confirms critical electronic transitions in the nanoparticle to be important for the redox buffering activity in the animal model. A careful administration of the developed nanoparticle not only reduces inflammatory markers in the animals, but also reduces the mortality rate from the induced disease. This study provides a proof of concept for the use of nanomaterial with synergistic anti-inflammatory and redox buffering capacity to prevent and treat ulcerative colitis.

Ultrasonic-assisted photocatalytic degradation of various organic contaminants using ZnO supported on a natural polymer of sporopollenin

Water resource pollution by organic contaminants is an environmental issue of increasing concern. Here, sporopollenin/zinc oxide (SP/ZnO) was used as an environmentally friendly and durable catalyst for sonophotocatalytic treatment of three organic compounds: direct blue 25 (DB 25), levofloxacin (LEV), and dimethylphtalate (DMPh). The resulting catalyst had a 2.65 eV bandgap value and 9.81 m2/g surface area. The crystalline structure and functional groups of SP/ZnO were confirmed by X-ray diffraction (XRD) and Fourier transforms infrared spectroscopy (FTIR) analyses. After 120 min of the sonophotocatalysis, the degradation efficiencies of DB 25, LEV, and DMPh by SP/ZnO were 86.41, 75.88, and 62.54%, respectively, which were higher than that of the other investigated processes. The role of reactive oxygen species were investigated using various scavengers, enhancers, photoluminescence, and o-phenylenediamine. Owing to its stability, the catalyst exhibited good reusability after four consecutive cycles. In addition, the high integrity of the catalyst was confirmed by scanning electron microscopy (SEM), XRD, and FTIR analyses. After four consecutive examinations, the leaching of zinc in the aqueous phase was < 3 mg/L. Moreover, gas chromatography-mass spectrometry (GC–MS) analyses indicated that the contaminants were initially converted into cyclic compounds and then into aliphatic compounds, including carboxylic acids and animated products. Thus, this study synthesized an environmentally friendly and reusable SP/ZnO composite for the degradation of various organic pollutants using a sonophotocatalytic process.

Taguchi L9 (34) Orthogonal Array Design for Photocatalytic Degradation of Methylene Blue Dye by Green ZnO Particles Biosynthesized by Chrysanthemum spp. Flower Extract

The pollution of synthetic dyes in wastewater exerts many negative impacts on the environment and human health. There is an increasing demand for the degradation of dyes, with an emphasis on photocatalysis. Here, we investigated the bio-mediated synthesis of ZnO using Chrysanthemum spp. flower extract and its utilization for the removal of methylene blue dye under sunlight irradiation. The bandgap energy of green ZnO nanoparticles was determined to be 3.0. The Taguchi L9 (34) orthogonal array design was applied to optimize the photocatalytic degradation of methylene blue dye by green ZnO particles. Four parameters, including the initial concentration (10–50 mg/L), ZnO dosage (0.33–1.0 mg), contact time (30–120 min), and pH (4–10) of the solution, were surveyed based on the Taguchi design. We found that the test result (99.0%) at 10 mg/L was almost equivalent to the predicted value (99.5%) of degradation efficiency. The reaction mechanisms shed light on the major role of reactive oxygen species (•O2−, •OH). More importantly, the green ZnO particles could be reused for at least five cycles and demonstrated high stability.

Cardioprotective effect of tamoxifen and raloxifene: Preventing proteoglycan synthesis by modulating non-canonical TGF-β signalling through NADPH oxidase and ERK phosphorylation

Atherosclerosis, a leading cause of cardiovascular disease, remains a significant global health concern. Tamoxifen and raloxifene, selective estrogen receptor modulators (SERMs), have demonstrated potential cardioprotective effects. However, the underlying molecular mechanisms by which these SERMs modulate Transforming Growth Factor-β (TGF-β) signaling in human vascular smooth muscle cells (VSMCs) remain largely unexplored. This study sought to investigate the impact of tamoxifen and raloxifene on TGF-β-induced CHSY1 expression and Smad2 linker region phosphorylation in VSMCs and to elucidate the role of reactive oxygen species (ROS), NADPH oxidase (NOX), and kinase pathways in mediating these effects.Employing a comprehensive experimental strategy, VSMCs were treated with TGF-β in the presence or absence of tamoxifen, raloxifene, and various pharmacological inhibitors. Subsequently, CHSY1 mRNA expression, Smad2C and Smad2L phosphorylation, ROS production, p47phox and ERK 1/2 phosphorylation were assessed. Our results revealed that tamoxifen and raloxifene significantly attenuated TGF-β-mediated CHSY1 mRNA expression and Smad2 linker region phosphorylation, without affecting the canonical TGF-β-Smad2C pathway. Furthermore, these compounds effectively inhibited ROS production, p47phox and ERK 1/2 phosphorylation, implicating the involvement of the TGF-β-NOX-ERK-Smad2L signaling cascade in their cardioprotective properties.This study provides a comprehensive understanding of the molecular mechanisms underlying the cardioprotective effects of tamoxifen and raloxifene in VSMCs, offering valuable insights for the development of targeted therapeutic strategies aimed at atherosclerosis prevention and the promotion of cardiovascular health.

Role of reactive oxygen species (ROS) in the regulation of adipogenic differentiation of human maxillary/mandibular bone marrow-derived mesenchymal stem cells.

Maxillary/mandibular bone marrow-derived mesenchymal stem cells (MBMSCs) exhibit a unique property of lower adipogenic potential than other bone marrow-derived MSCs. However, the molecular mechanisms regulating the adipogenesis of MBMSCs remain unclear. This study aimed to explore the roles of mitochondrial function and reactive oxygen species (ROS) in regulating the adipogenesis of MBMSCs. MBMSCs exhibited significantly lower lipid droplet formation than iliac BMSCs (IBMSCs). Moreover, the expression levels of CCAAT/enhancer-binding protein β (C/EBPβ), C/EBPδ, and early B cell factor 1 (Ebf-1), which are early adipogenic transcription factors, and those of peroxisome proliferator-activated receptor-γ (PPARγ) and C/EBPα, which are late adipogenic transcription factors, were downregulated in MBMSCs compared to those in IBMSCs. Adipogenic induction increased the mitochondrial membrane potential and mitochondrial biogenesis in MBMSCs and IBMSCs, with no significant difference between the two cell types; however, intracellular ROS production was significantly enhanced only in IBMSCs. Furthermore, NAD(P)H oxidase 4 (NOX4) expression was significantly lower in MBMSCs than in IBMSCs. Increased ROS production in MBMSCs by NOX4 overexpression or treatment with menadione promoted the expression of early adipogenic transcription factors but did not induce that of late adipogenic transcription factors or lipid droplet accumulation. These results suggest that ROS may be partially involved in the process of MBMSC adipogenic differentiation from undifferentiated cells to immature adipocytes. This study provides important insights into the tissue-specific properties of MBMSCs.

Silk Fibroin Nanozyme Hydrogel with Self-Supplied H2O2 for Enhanced Antibacterial Therapy

Peroxidase-mimicking nanozyme therapy has emerged as a powerful tool in antibacterial therapy. Due to the critical role in reactive oxygen species (ROS) generation, various in situ H2O2 supplying nanoagents have been developed to guarantee the therapeutic effect. However, the challenges in reliance on external stimulus, instability of the H2O2 donor, and risk of leakage limited their antibacterial efficiency and actual application. In this work, we fabricated an injectable silk fibroin/ZnO NP/mica–Fe3O4 (SFZM) composite nanozyme hydrogel with spontaneous H2O2 generation and peroxidase-mimicking nanozyme properties. The ZnO NPs could produce H2O2 without light or other external stimulus. Under a weak acid environment, the H2O2 produced from ZnO NPs could be in situ transformed to ROS by magnetic mica–Fe3O4 nanosheets, leading to nearly 50% enhancement in antibacterial activity compared with a silk fibroin–ZnO hydrogel. Meanwhile, the SFZM nanozyme hydrogel displayed in vivo adhesion and hemostasis properties. As a result, the SFZM hydrogel could accelerate the healing of bacteria-infected wounds in rats. More interestingly, the ZnO exhibited continued H2O2 generation during at least 12 days, suggesting the long-term enhanced antibacterial effect of the SFZM hydrogel. Also, the SFZM nanozyme hydrogel showed low nanomaterial leakage and demonstrated biocompatibility both in vitro and in vivo.

Antioxidants and Sports Performance.

The role of reactive oxygen species and antioxidant response in training adaptations and sports performance has been a large issue investigated in the last few years. The present review aims to analyze the role of reactive oxygen species and antioxidant response in sports performance. For this aim, the production of reactive oxygen species in physical activities, the effect of reactive oxygen species on sports performance, the relationship between reactive oxygen species and training adaptations, inflammation, and the microbiota, the effect of antioxidants on recovery and sports performance, and strategies to use antioxidants supplementations will be discussed. Finally, practical applications derived from this information are discussed. The reactive oxygen species (ROS) production during physical activity greatly influences sports performance. This review concludes that ROS play a critical role in the processes of training adaptation induced by resistance training through a reduction in inflammatory mediators and oxidative stress, as well as appropriate molecular signaling. Additionally, it has been established that micronutrients play an important role in counteracting free radicals, such as reactive oxygen species, which cause oxidative stress, and the effects of antioxidants on recovery, sports performance, and strategies for using antioxidant supplements, such as vitamin C, vitamin E, resveratrol, coenzyme Q10, selenium, and curcumin to enhance physical and mental well-being.

Chronic anemia is associated with systemic endothelial dysfunction.

In acute myocardial infarction and heart failure, anemia is associated with adverse clinical outcomes. Endothelial dysfunction (ED) is characterized by attenuated nitric oxide (NO)-mediated relaxation responses which is poorly studied in chronic anemia (CA). We hypothesized that CA is associated with ED due to increased oxidative stress in the endothelium. CA was induced by repeated blood withdrawal in male C57BL/6J mice. Flow-Mediated Dilation (FMD) responses were assessed in CA mice using ultrasound-guided femoral transient ischemia model. Tissue organ bath was used to assess vascular responsiveness of aortic rings from CA mice, and in aortic rings incubated with red blood cells (RBCs) from anemic patients. In the aortic rings from anemic mice, the role of arginases was assessed using either an arginase inhibitor (Nor-NOHA) or genetic ablation of arginase 1 in the endothelium. Inflammatory changes in plasma of CA mice were examined by ELISA. Expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS), myeloperoxidase (MPO), 3-Nitrotyrosine levels, and 4-Hydroxynonenal (4-HNE) were assessed either by Western blotting or immunohistochemistry. The role of reactive oxygen species (ROS) in ED was assessed in the anemic mice either supplemented with N-Acetyl cysteine (NAC) or by in vitro pharmacological inhibition of MPO. The FMD responses were diminished with a correlation to the duration of anemia. Aortic rings from CA mice showed reduced NO-dependent relaxation compared to non-anemic mice. RBCs from anemic patients attenuated NO-dependent relaxation responses in murine aortic rings compared to non-anemic controls. CA results in increased plasma VCAM-1, ICAM-1 levels, and an increased iNOS expression in aortic vascular smooth muscle cells. Arginases inhibition or arginase1 deletion did not improve ED in anemic mice. Increased expression of MPO and 4-HNE observed in endothelial cells of aortic sections from CA mice. NAC supplementation or inhibition of MPO improved relaxation responses in CA mice. Chronic anemia is associated with progressive endothelial dysfunction evidenced by activation of the endothelium mediated by systemic inflammation, increased iNOS activity, and ROS production in the arterial wall. ROS scavenger (NAC) supplementation or MPO inhibition are potential therapeutic options to reverse the devastating endothelial dysfunction in chronic anemia.