Rate Reactive Oxygen Species Research Articles

A novel method in radish processing: Augmented flavor and health benefits revealed through Caenorhabditis elegans model

This study investigates the preparation of black radish using a cyclic method involving alternating 75 °C baking and 100 °C steam treatment for 10 cycles. Compared to fresh radish, black radish contains higher concentrations of quinolines and amino acids, giving it a rich taste and caramel aroma. Black radish extract contains quinoline and ornithine levels that are 198.92 times and 94.48 times greater, respectively, than those in fresh radish extract. Black radish extract demonstrates superior performance in reducing fat accumulation and enhancing antioxidant capacity. At a concentration of 10 μg/mL, black radish extract reduces the relative Oil Red O intensity in Caenorhabditis elegans to 13.42%. At a concentration of 1000 μg/mL, black radish extract achieves a 24.93% inhibition rate of reactive oxygen species. Additionally, the black radish extract does not exhibit significant toxic effects on various physiological functions of C. elegans and notably enhances their lifespan.

Analysis of Intact In Vivo Peroxidized Phospholipids from Bovine Retina via LC-MS/MS and GC-MS/MS Using Autoxidized Retina Reference Standards.

Highly unsaturated fatty acids (HUFAs) are vulnerable to oxygen attack, thus making HUFA-rich, high metabolic rate/reactive oxygen species (ROS)-generating neurological tissue particularly susceptible to increased oxidative stress. Lipid oxidation is a putative early stage marker of neurodegenerative diseases, suggesting that reliable monitoring of oxidized neural lipids in vivo reveals early pathogenesis. Here, we present a novel methodology to detect and quantify intactin vivo ROS-driven peroxidized phospholipids (LPOx-PLs) in bovine retina extract. A protocol for preparing autoxidized pure phospholipids (PLs) and complex retinal extracts served as reference standards and was adapted to enable analytical parameter development. Fatty acid profiles of bovine retinas were first established with routine gas chromatography (GC) methods and used to customize mass spectrometry scanning for major HUFA-carrying PLs in the retinal extract. Targeted multiple reaction monitoring (MRM) scanning via triple quadrupole tandem mass spectrometry detected native (unoxidized) and oxidation-damaged PL regardless of the position of the O or O2 addition along the acyl chains and enabled quantification of relative signals from intact native and oxidized PL (5%-10% CV). MRM-triggered information-dependent acquisition (IDA) spectra confirmed the structure of peroxidized PLs, revealing that peroxidized species (+O-OH) dominated over single O-added species in vitro and in vivo. Positive identification and relative quantification are reported for 12 selected in vivo native and peroxidized phosphatidylcholines and phosphatidylethanolamines. These results enable future studies of the initial peroxidation due to toxins, genetics, or other initiating events influencing in vivo oxidation levels and potentially the effectiveness of strategies to mitigate this mechanism of action.

Ozone nanobubble technology as a novel AOPs for pollutants degradation under high salinity conditions

Conventional water treatment systems frequently exhibit diminished efficiency at high salinity - a significant issue especially for real industrial effluents - mostly due to the creation of intricate structures between pollutants and salts. One of the primary obstacles associated with high salinity conditions is the generation of by-products that pose additional hurdles for treatment. In this work, we have investigated the novel advanced oxidation process a so-called ozone nanobubble technology for degradation of the pollutants at high salinity conditions. The mass transfer is often the rate-limiting step in gas-liquid process and the poor rate of mass transfer diminishes the overall efficacy. One of the primary disadvantages associated with ozone is its restricted solubility and instability when dissolved in an aqueous solution. These characteristics impose limitations on its potential applications and need the use of specialized systems to facilitate gas-liquid interaction. In this work, we have also suggested enhancing the ozonation process through the utilization of ozone nanobubbles. The findings of our experiment and subsequent analysis indicate that the presence of nanobubbles enhances the process of ozonation through three key mechanisms: (i) an increased mass transfer coefficient, (ii) a higher rate of reactive oxygen species (ROS) generation attributed to the charged interface, and (iii) the nanobubble interface serving as an active surface for chemical reactions. The predicted mass transfer coefficients were found to range from 3 to 3.5 min−1, a value that is notably greater than that seen for microbubbles. The study showcased the degradation of methylene blue dye through the utilization of ozone nanobubbles, which exhibited a much higher rate of dye degradation compared to ozone microbubbles. The confirmation of the radical degradation mechanism was achieved by the utilization of electron spin resonance (ESR) measurements. The developed process has high potential for application in industrial scale textile wastewater treatment.

Enhancing degradation of sulfamethoxazole by layered double hydroxide/carbon nanotubes catalyst via synergistic effect of photocatalysis/persulfate activation

A Co3Mn-LDHs and carbon nanotube (Co3Mn-LDHs/CNT) composite catalyst was constructed for permonosulfate (PMS) activation and degrading sulfamethoxazole (SMX) under Vis light irradiation. The introduction of CNTs into Co3Mn-LDHs facilitate the exciton dissociation and carrier migration, and the e− and h+ were readily separated from Co3Mn-LDHs/CNT in the photocatalysis process, which promoted the production rate of reactive oxygen species (ROS), so the Co3Mn-LDHs + Vis + PMS system exhibited better activity with an SMX degradation ratio of 61.25% than those of Co3Mn-LDHs + Vis system (42.30%) and Co3Mn-LDHs + PMS system (48.30%). After 10 cycles, the degradation rate of SMX only decreased by 7.16%, indicating the good reusability of the Co3Mn-LDHs/CNTs catalyst. The results of electron paramagnetic resonance (EPR) analysis and radical quenching experiments demonstrated that that the SO4•− played crucial role for SMX removal in Co3Mn-LDHs/CNTs + Vis + PMS system, and both e− and h+ made an important contribution to activating PMS to produce ROS. Overall, this work provided an excellent catalyst for photo-assisted PMS activation and suggested the activation mechanism for organic pollutant remediation.

Antioxidant, Anti-photoaging, and Anti-wrinkle Effects of Cosmetics Containing Low-molecular-weight Peptide Complexes

Purpose: This study aimed to confirm the skin improvement effects of cosmetics containing low-molecular-weight peptide complexes using <i>in vitro</i> and human application tests.Methods: An <i>in vitro</i> test was conducted to confirm the cytotoxicity, antioxidant, and anti-photoaging effects of cosmetics comprising low-molecular-weight peptide complexes. The protective effect on HacaT cells subjected to oxidative stress and collagen production in CCD-986sk cells irradiated with UV-B (Ultraviolet B) were confirmed. Moreover, to validate skin improvement effects, a human application test was performed on 20 adults aged 30–59 years. The wrinkles depth and the indentation index around the forehead, eyes, cheeks, and mouth were evaluated using ANTERA 3D CS.Results: The test material demonstrated excellent cell viability, confirming its safety on the skin. At a concentration of 0.1%, it exhibited a removal rate of reactive oxygen species (ROS) by 63.39% (<i>p</i><0.001) and an increase in collagen content of 102.14% (<i>p</i><0.01). Furthermore, in the human application test over 4 weeks, skin folds exhibited a decrease in average depth by 20.53% (<i>p</i><0.001), and the indentation index decreased by 17.02% (<i>p</i><0.001).Conclusion: Cosmetics containing low-molecular-weight peptide complexes possess excellent antioxidant, anti-photoaging, and collagen synthesis promotion properties. Their efficacy in reducing skin wrinkles and increasing skin elasticity was also confirmed. Low-molecular-weight peptide complexes could be an excellent active ingredient in cosmeceuticals.

The impact of hollow core-shell nanozymes in biosensing: A case study of p-Fe3O4@PDA@ZIF-67

BackgroundNanozymes, a new class of nanomaterials, have emerged as promising substitutes for enzymes in biosensor design due to their exceptional stability, affordability, and ready availability. While nanozymes address many limitations of natural enzymes, they still face challenges, particularly in achieving the catalytic activity levels of their natural counterparts. This indicates the need for enhancing the sensitivity of biosensors based on nanozymes. The catalytic activity of nanozyme can be significantly improved by regulating its size, morphology, and surface composition of nanomaterial. ResultsIn this work, a kind of hollow core-shell structure was designed to enhance the catalytic activity of nanozymes. The hollow core-shell structure material consists of a nanozymes core layer, a hollow layer, and a MOF shell layer. Taking the classic peroxidase like Fe3O4 as an example, the development of a novel nanozyme@MOF, specifically p-Fe3O4@PDA@ZIF-67, is detailed, showcasing its application in enhancing the sensitivity of sensors based on Fe3O4 nanozymes. This innovative nanocomposite, featuring that MOF layer was designed to adsorb the signal molecules of the sensor to improve the utilization rate of reactive oxygen species generated by the nanozymes catalyzed reactions and the hollow layer was designed to prevent the active sites of nanozymes from being cover by the MOF layer. The manuscript emphasizes the nanocomposite's remarkable sensitivity in detecting hydrogen peroxide (H2O2), coupled with high specificity and reproducibility, even in complex environments like milk samples. Significance and noveltyThis work firstly proposed and proved that Fe3O4 nanozyme@MOF with hollow layer structure was designed to improve the catalytic activity of the Fe3O4 nanozyme and the sensitivity of the sensors based on Fe3O4 nanozyme. This research marks a significant advancement in nanozyme technology, demonstrating the potential of structural innovation in creating high-performance, sensitive, and stable biosensors for various applications.

Metformin-Mediated Fast Charge-Reversal Nanohybrid for Deep Penetration Piezocatalysis-Augmented Chemodynamic Immunotherapy of Cancer.

Immune checkpoint blockade (ICB) therapy still suffers from insufficient immune response and adverse effect of ICB antibodies. Chemodynamic therapy (CDT) has been demonstrated to be an effective way to synergize with ICB therapy. However, a low generation rate of reactive oxygen species and poor tumor penetration of CDT platforms still decline the immune effects. Herein, a charge-reversal nanohybrid Met@BF containing both Fe3O4 and BaTiO3 nanoparticles in the core and Metformin (Met) on the surface was fabricated for tumor microenvironment (TME)- and ultrasound (US)-activated piezocatalysis-chemodynamic immunotherapy of cancer. Interestingly, Met@BF had a negative charge in blood circulation, which was rapidly changed into positive when exposed to acidic TME attributed to quaternization of tertiary amine in Met, facilitating deep tumor penetration. Subsequently, with US irradiation, Met@BF produced H2O2 based on piezocatalysis of BaTiO3, which greatly enhanced the Fenton reaction of Fe3O4, thus boosting robust antitumor immune response. Furthermore, PD-L1 expression was inhibited by the local released Met to further augment the antitumor immune effect, achieving effective inhibitions for both primary and metastatic tumors. Such a combination of piezocatalysis-enhanced chemodynamic therapy and Met-mediated deep tumor penetration and downregulation of PD-L1 provides a promising strategy to augment cancer immunotherapy.

A multifactorial study of in situ antioxidant activity of modified GrO in myocardial reperfusion injury using the Langerdorff model

Carbon nanomaterials possess antioxidant properties that can be applied in biomedicine and clinics for the development of new highly effective treatments against oxidative stress-induced diseases like ischemic heart disease. We previously reported the usage of graphene oxide (GrO) as a precursor for the elaboration of such prototypes. The promising findings led to the development of two new modifications of GrO: nitrogen-doped (N-GrO) and l-cysteine functionalized (S-GrO) derivatives as possible antioxidant agents in ischemia-reperfusion (I/R) conditions. In this study, the cardioprotective and antioxidant potential of modified GrO as a pre-treatment in rats was evaluated for the first time. In Langendorff isolated rat heart I/R model, the left ventricle developed pressure (LVDP), the end-diastolic pressure (EDP), the maximal (dP/dtmax) and minimal (dP/dtmin) value of the first derivative of LVDP, and heart rate (HR) were measured. The oxidative-nitrosative markers, in particular, the rate of O2*- and H2O2 generation, the content of malonic dialdehyde, diene conjugates, and leukotriene as well as cNOS and iNOS activity were estimated. Obtained results show a significant restoration of cadiodynamic parameters at the reperfusion period. Simultaneously, all samples significantly reduced the rate of reactive oxygen species (ROS) and lipid peroxidation markers in cardiac homogenates and preserved cNOS activity at the preischemic level. This evidence makes GrO derivatives promising candidates for the correction of reperfusion disorders affecting myocardial function.

A type I and type II chemical biology toolbox to overcome the hypoxic tumour microenvironment for photodynamic therapy.

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality employed for the treatment of various types of cancers, localized infections, and other diseases. Upon illumination, the photo-excited photosensitizer generates singlet oxygen and other reactive species, thereby inducing cytotoxicity in the target cells. The hypoxic tumour microenvironment (TME), however, poses a limitation on the supply of oxygen in tumour tissues. Moreover, under such conditions, tumour metastasis and drug resistance frequently occur, further compromising the efficacy of PDT in combating tumours. Traditionally, type I photosensitizers with lower oxygen consumption demonstrate significant potential in overcoming hypoxic environments and play a crucial role in determining the therapeutic efficacy of PDT because type I photosensitizers can generate highly cytotoxic free radicals. In comparison, type II photosensitizers exhibit high oxygen dependence. The rate of reactive oxygen species (ROS) generation in the type II process is significantly higher than that in the type I process. Thus, the efficiency and selectivity of PDT depend on the properties of the photosensitizer. Here, the recent development and application of type I and type II photosensitizers, mainly in the past year, are summarized. The design methods, electronic structures, photophysical properties, lipophilic properties, electric charge, and other molecular characteristics of these photosensitizers are discussed in detail. These modifications alter the microstructure of photosensitizers and directly impact the results of PDT. The main content of this paper will have a positive promoting and inspiring effect on the future development of PDT.

The study of the protective effect of mitochondrial uncouplers during acute toxicity of the fungicide difenoconazole in different organs of mice.

Pesticides represent a serious problem for agricultural workers due to their neurotoxic effects. The aim of this study was to evaluate the ability of pharmacological oxidative phosphorylation uncouplers to reduce the effect of the difenoconazole fungicide on mitochondrial DNA (mtDNA) of various organs in mice. Injections of difenoconazole caused cognitive deficits in mice, and the protonophore 2,4-dinitrophenol (2,4-DNP) and Azur I (AzI), a demethylated metabolite of methylene blue (MB), prevented the deterioration of cognitive abilities in mice induced by difenoconazole. Difenoconazole increased the rate of reactive oxygen species (ROS) production, likely through inhibition of complex I of the mitochondrial respiratory chain. After intraperitoneal administration of difenoconazole lungs, testes and midbrain were most sensitive to the accumulation of mtDNA damage. In contrast, the cerebral cortex and hippocampus were not tolerant to the effects of difenoconazole. The protonophore 2,4-DNP reduced the rate of ROS formation and significantly reduced the amount of mtDNA damage caused by difenoconazole in the midbrain, and partially, in the lungs and testes. MB, an alternative electron carrier capable of bypassing inhibited complex I, had no effect on the effect of difenoconazole on mtDNA, while its metabolite AzI, a demethylated metabolite of MB, was able to protect the mtDNA of the midbrain and testes. Thus, mitochondria-targeted therapy is a promising approach to reduce pesticide toxicity for agricultural workers.

The Role of the Ascorbic Acid-Glutathione Cycle in Young Wheat Ears' Response to Spring Freezing Stress.

Freezing stress in spring often causes the death and abnormal development of young ears of wheat, leading to a significant reduction in grain production. However, the mechanisms of young wheat ears responding to freezing are largely unclear. In this study, the role of the ascorbic acid-glutathione cycle (AsA-GSH cycle) in alleviating freezing-caused oxidative damage in young wheat ears at the anther connective tissue formation phase (ACFP) was investigated. The results showed that the release rate of reactive oxygen species (ROS) and the relative electrolyte conductivity in young ears of Jimai22 (JM22, freezing-tolerant) were significantly lower than those in young ears of Xumai33 (XM33, freezing-sensitive) under freezing. The level of the GSH pool (231.8~392.3 μg/g FW) was strikingly higher than that of the AsA pool (98.86~123.4 μg/g FW) in young wheat ears at the ACFP. Freezing significantly increased the level of the AsA pool and the activities of ascorbate peroxidase (APX) and monodehydroascorbate reductase (MDHAR) in the young ears of both varieties. The level of the GSH pool increased in the young ears of XM33 under freezing but decreased in the young ears of JM22. The young ears of JM22 showed higher activities of glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione peroxidase (GPX) than the young ears of XM33 under freezing. Collectively, these results suggest that the AsA-GSH cycle plays a positive role in alleviating freezing-induced oxidative damage in young wheat ears. Furthermore, the ability of utilizing GSH as a substrate to scavenge ROS is an important factor affecting the freezing tolerance of young wheat ears. In addition, abscisic acid (ABA), salicylic acid (SA), 3-indolebutyric acid (IBA) and cis-zeatin (cZ) may be involved in regulating the AsA-GSH cycle metabolism in young wheat ears under freezing.

CuO/ZnO Type-II heterojunction modified by rGO nanosheets for improved photocatalytic mineralization of antibiotics

In the present work, CuO/ZnO type-II heterojunction was modified by graphene oxide nanosheets for excellent photocatalytic mineralization of antibiotics under artificial UV light and natural sunlight. For this purpose, CuO/ZnO heterojunction-graphene oxide nanocomposites were synthesized via a facile refluxing method in aqueous media. The synthesized nanocomposites were characterized through diverse characterization techniques such as XRD, FT- IR, Raman, SEM, TEM, and UV–Vis DRS to determine their structural, morphological, and optical properties. XRD analysis confirmed the monoclinic CuO and hexagonal wurtzite ZnO phase in bare CuO/ZnO heterojunction and different CuO/ZnO heterojunction-graphene oxide nanocomposites as well. The optical band gap was found in the range of 3.06–3.19 eV for different nanocomposites. The photocatalytic activity of the bare heterojunction and nanocomposites was performed against the degradation of ciprofloxacin under the irradiation of artificial UV and natural sunlight as well. The highest degradation % of ciprofloxacin was achieved at 96.27 % and 76.44 % under artificial UV and natural sunlight within 120 min, respectively over CuO/ZnO heterojunction with 3 wt% of graphene oxide. The outstanding photocatalytic performance of CuO/ZnO heterojunction-graphene oxide (3 wt%) owing to the high adsorption capacity and synergism between CuO/ZnO and graphene oxide caused the improved separation of charge species resulting higher production rate of reactive oxygen species and prompt degradation of ciprofloxacin.

Assessment of Bacillus subtilis fermented Caulerpa microphysa byproduct as feed additive on the growth performance, immune regulation and disease resistance of white shrimp (Litopenaeus vannamei)

In this study, the immunomodulatory and antioxidant activity of fermented Caulerpa microphysa byproduct (FCMB) by Bacillus subtilis was evaluated, and its potential as a feed additive for white shrimp (Litopenaeus vannamei) was explored. In vitro experiments showed that the FCMB supernatant contained polysaccharides, polyphenols and flavonoids, and exhibited antioxidant properties as assessed by various antioxidant assays. Additionally, the FCMB supernatant was found to increase the production rate of reactive oxygen species and the activity of phenoloxidase in hemocytes in vitro. Furthermore, the results of the in vivo feeding trial showed that dietary 5 g kg−1 FCMB significantly improved the weight gain and specific growth rate of white shrimp after 56 days of feeding. Although there were no significant differences in total hemocyte count, phagocytosis, superoxide anion production rate, and phenoloxidase activity among the experimental groups, upregulation of immune-related genes was observed, particularly in the hepatopancreas and hemocytes of shrimps fed with 5 g or 50 g FCMB per kg feed, respectively. In the pathogen challenge assay, white shrimp fed with 5 % FCMB exhibited a higher survival rate compared to the control group following Vibrio parahaemolyticus challenge. Therefore, it is concluded that the fermented byproduct of C. microphysa, FCMB, holds potential as a feed additive for enhancing the growth performance and disease resistance against V. parahaemolyticus in white shrimp.

Nrf2 protein in melanoma progression, as a new means of treatment.

Melanoma is a potentially lethal form of skin cancer resulting from the unlimited proliferation of melanocytes. Melanocytic lineage appears to have a greater rate of reactive oxygen species (ROS) production, possibly as a result of exposure to ultraviolet (UV) light and the production of melanin. It has been established that nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a master regulator of the cellular response to oxidative stresses. Recent research has shown that the Nrf2 and its critical negative regulator Kelch-like ECH-associated protein 1 (Keap1) are misregulated in melanoma, and the Keap1-Nrf2 pathway has emerged as a promising new target for treating and preventing melanoma. In melanoma, Nrf2 may either limit tumor growth or promote its development. This review covers a wide range of topics, including the dual functions played by the Keap1-Nrf2 signaling pathway in melanoma and the most recent targeting techniques of the Nrf2.

Lactoferrin: neuroprotection against Parkinson's disease and secondary molecule for potential treatment.

Parkinson's disease (PD) is the second-most common neurodegenerative disease and is largely caused by the death of dopaminergic (DA) cells. Dopamine loss occurs in the substantia nigra pars compacta and leads to dysfunctions in motor functions. Death of DA cells can occur with oxidative stress and dysfunction of glial cells caused by Parkinson-related gene mutations. Lactoferrin (Lf) is a multifunctional glycoprotein that is usually known for its presence in milk, but recent research shows that Lf is also found in the brain regions. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a known mitochondrial toxin that disturbs the mitochondrial electron transport chain (ETC) system and increases the rate of reactive oxygen species. Lf's high affinity for metals decreases the required iron for the Fenton reaction, reduces the oxidative damage to DA cells caused by MPTP, and increases their surveillance rate. Several studies also investigated Lf's effect on neurons that are treated with MPTP. The results pointed out that Lf's protective effect can also be observed without the presence of oxidative stress; thus, several potential mechanisms are currently being researched, starting with a potential HSPG-Lf interaction in the cellular membrane of DA cells. The presence of Lf activity in the brain region also showed that lactoferrin initiates receptor-mediated transcytosis in the blood-brain barrier (BBB) with the existence of lactoferrin receptors in the endothelial cells. The existence of Lf receptors both in endothelial cells and DA cells created the idea of using Lf as a secondary molecule in the transport of therapeutic agents across the BBB, especially in nanoparticle development.

Bespoke selenium nanowires with comprehensive piezo-phototronic effects as viable p-type semiconductor-based piezo-photocatalysts

As the demand for environmental purification and energy harvesting continues to grow, research on maximizing the efficiency of catalysts is attracting great attention. The piezo-phototronic effect has emerged as an effective strategy to enhance the photocatalytic activity of semiconductors. While p-type semiconductors exhibit high photoresponsivity across a wide spectral range, their potential as piezo-photocatalysts has been limited due to their low carrier concentration and inferior carrier migration behavior. Therefore, it is hypothesized that overcoming these limitations would allow p-type semiconductors to achieve catalytic performance comparable to, or even surpassing, that of n-type systems. Here, we introduce two effective strategies into p-type trigonal selenium nanowires (Se NWs): electron-proton co-doping and localized surface plasmon resonance effect. These approaches improve the light absorption capacity, charge transport ability, and piezoelectricity, thereby significantly enhancing the piezo-photocatalytic performance. Under the influence of the piezo-phototronic effect, the post-treated Se NWs exhibit markedly enhanced evolution rates of reactive oxygen species compared to pure Se NWs. Consequently, the degradation efficiency of organic contaminants is increased up to 4-fold. This breakthrough opens up a new pathway for the development of p-type piezoelectric materials, which can potentially replace their n-type counterparts in catalytic applications.

The Impact of Cerium Oxide Nanoparticles on Reactive Oxygen Species (ROS) Release Rate in Mice Organs

The impact of exposing significant mouse organs to cerium oxide nanoparticles (CeO2 NPs) has received considerable attention in the literature, but a comprehensive review on this topic is lacking. This review aims to address this gap by examining the influence of CeO2 NPs on the release rate of reactive oxygen species (ROS) in various organs of mice. CeO2 NPs have demonstrated potential therapeutic applications due to their ROS-scavenging abilities, which are relevant to oxidative stress-related diseases. Recent studies investigating the effect of CeO2 NPs on ROS release rate in organs such as the liver, spleen, lung, and brain are highlighted in this article. The findings reveal a complex interaction between CeO2 NPs and the ROS system, influenced by factors such as particle dose, size, and surface chemistry. Furthermore, the impact of CeO2 NPs on ROS release rate is organ-specific and dependent on the tissue microenvironment. The review also addresses the potential toxicity of CeO2 NPs and emphasizes the need for further research to better comprehend their mechanisms of action and long-term effects. By providing valuable insights into the influence of CeO2 NPs on ROS release rate in mice organs, this review holds significant implications for the therapeutic applications of CeO2 NPs in oxidative stress-related diseases. This review contributes to the existing body of knowledge by examining the impact of CeO2 NPs on ROS release rate in various mouse organs

1,25-Dihydroxyvitamin D3 alleviates hyperandrogen-induced ferroptosis in KGN cells

PurposeHyperandrogenism, one of the most frequent causes of anovulation in women, increases the risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS). Ferroptosis, characterized by iron-dependent lipid peroxidation, has provided new insight into the progression of PCOS. 1,25-dihydroxyvitamin D3 (1,25D3) may play a role in reproduction because its receptor, VDR, which contributes to the inhibition of oxidative stress, is primarily located in the nuclei of granulosa cells. This study has therefore investigated whether 1,25D3 and hyperandrogenism affect granulosa-like tumor cells (KGN cells) through ferroptosis.MethodsKGN cells were treated with dehydroepiandrosterone (DHEA) or pretreated with 1,25D3. Cell viability was evaluated with the cell counting kit-8 (CCK-8) assay. The mRNA and protein expression levels of ferroptosis-related molecules, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member (SLC7A11), and long-chain acyl-CoA synthetase 4 (ACSL4), were assessed via qRT–PCR and western blot. The concentration of malondialdehyde (MDA) was measured by ELISA. The rates of reactive oxygen species (ROS) production and lipid peroxidation were assessed via photometric methods.ResultsDecreased cell viability, suppression of GPX4 and SLC7A11 expression, increased expression of ACSL4, elevated levels of MDA, accumulation of ROS, and increased lipid peroxidation, which are changes representative of ferroptosis, were observed in KGN cells after treatment with DHEA. Pretreatment with 1,25D3 in KGN cells significantly prevented these changes.ConclusionsOur findings demonstrate that 1,25D3 attenuates hyperandrogen-induced ferroptosis of KGN cells. This finding might lead to new insights into the pathophysiology and therapy of PCOS and provides new evidence for the treatment of PCOS with 1,25D3.

HPRT1 Deficiency Induces Alteration of Mitochondrial Energy Metabolism in the Brain

Alterations in function of hypoxanthine guanine phosphoribosyl transferase (HPRT), one of the major enzymes involved in purine nucleotide exchange, lead to overproduction of uric acid and produce various symptoms of Lesch-Nyhan syndrome (LNS). One of the hallmarks of LNS is maximal expression of HPRT in the central nervous system with the highest activity of this enzyme in the midbrain and basal ganglia. However, the nature of neurological symptoms has yet to be clarified in details. Here, we studied whether HPRT1 deficiency changes mitochondrial energy metabolism and redox balance in murine neurons from the cortex and midbrain. We found that HPRT1 deficiency inhibits complex I-dependent mitochondrial respiration resulting in increased levels of mitochondrial NADH, reduction of the mitochondrial membrane potential, and increased rate of reactive oxygen species (ROS) production in mitochondria and cytosol. However, increased ROS production did not induce oxidative stress and did not decrease the level of endogenous antioxidant glutathione (GSH). Thus, disruption of mitochondrial energy metabolism but not oxidative stress could play a role of potential trigger of brain pathology in LNS.

Antioxidant and Antineuroinflammatory Mechanisms of Kaempferol-3-O-β-d-Glucuronate on Lipopolysaccharide-Stimulated BV2 Microglial Cells through the Nrf2/HO-1 Signaling Cascade and MAPK/NF-κB Pathway.

Aglycone- and glycoside-derived forms of flavonoids exist broadly in plants and foods such as fruits, vegetables, and peanuts. However, most studies focus on the bioavailability of flavonoid aglycone rather than its glycosylated form. Kaempferol-3-O-β-d-glucuronate (K3G) is a natural flavonoid glycoside obtained from various plants that have several biological activities, including antioxidant and anti-inflammatory effects. However, the molecular mechanism related to the antioxidant and antineuroinflammatory activity of K3G has not yet been demonstrated. The present study was designed to demonstrate the antioxidant and antineuroinflammatory effect of K3G against lipopolysaccharide (LPS)-stimulated BV2 microglial cells and to evaluate the underlying mechanism. Cell viability was determined by MTT assay. The inhibition rate of reactive oxygen species (ROS) and the production of pro-inflammatory mediators and cytokines were measured by DCF-DA assay, Griess assay, enzyme-linked immunosorbent assay (ELISA), and western blotting. K3G inhibited the LPS-induced release of nitric oxide, interleukin (IL)-6, and tumor necrosis factor-α (TNF-α) as well as the expression of prostaglandin E synthase 2. Additionally, K3G reduced the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB) related proteins. Mechanistic studies found that K3G downregulated phosphorylated mitogen-activated protein kinases (MAPKs) and upregulated the Nrf2/HO-1 signaling cascade. In this study, we demonstrated the effects of K3G on antineuroinflammation by inactivating phosphorylation of MPAKs and on antioxidants by upregulating the Nrf2/HO-1 signaling pathway through decreasing ROS in LPS-stimulated BV2 cells.