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A benzothiazole-based derivative aggregation-induced emission (AIE) fluorescent 'turn-on' probe named 2-(2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)phenyl)benzo[d]thiazole (probe BT-BO) was developed and synthesized successfully for detecting hydrogen peroxide (H2O2) in living cells. The synthesis method of probe BT-BO is facile. Probe BT-BO demonstrates a well-resolved emission peak at 604 nm and the ability to prevent the interference of reactive oxygen species (ROS), various metal ions and anion ions, and good sensitivity. Additionally, the probe boasts impressive pH range versatility, a fast response time to H2O2 and low cytotoxicity. Finally, probe BT-BO was applied successfully to image A549 and Hep G2 cells to monitor both exogenous and endogenous H2O2. [ABSTRACT FROM AUTHOR]

Studies on particulate air pollution indicate that a new type of pollutant should be considered from mainly fossil fuel combustion and automobile exhaust emissions, i.e., environmentally persistent free radicals. These radicals, ubiquitous in the environment, have a long life span and are capable of producing harmful reactive oxygen species. Samples of dandelion were collected in 2020 and 2021 in spring and late summer. Roots, leaves, flower stalks, and inflorescences of Taraxacum sp. were collected from six sites with three plants each, along with monitoring of particulate matter air pollution. Four sites were located at streets with heavy traffic and two were control sites in the rural part of the city. The free radical content in each part of the plant was measured by electron paramagnetic resonance. The leaf was selected as the most appropriate part of the plant for the measurement of carbon-derived free radicals. The geff value and the total number of spins were calculated. Relationships were found between location, season, and measurements. The electron paramagnetic resonance spectrum consists of at least two components, which can be attributed to C-type radicals and mixed C + O radicals. Their increase in numbers in the fall seasons, compared to the spring seasons, is also noticeable. It has also been observed that leaves collected in autumn have a higher geff value, which is probably related to the higher amount of oxygen- and carbon-derived free radicals. [ABSTRACT FROM AUTHOR]

A series of β-carboline derivatives containing nitrogen heterocycles were designed and synthesized. All compounds were screened for their antitumor activity against four human tumor cell lines (A549, K562, PC-3, T47D). Notably, compound N-(4-(morpholinomethyl)phenyl)-2-((5-(1-(3,4,5-trimethoxyphenyl)-9H-pyrido[3,4-b]indol-3-yl)-1,3,4-oxadiazol-2-yl)thio)acetamide (8q) exhibited significant inhibitory activity against PC-3 cells with an IC50 value of 9.86 µM. Importantly, compound 8q effectively suppressed both the proliferation and migration of PC-3 cells. Mechanistic studies revealed that compound 8q induced cell apoptosis and caused the accumulation of reactive oxygen species (ROS), leading to cell cycle arrest in the G0/G1 phase in PC-3 cells. [ABSTRACT FROM AUTHOR]

We report a green and efficient visible-light-driven method for the arylation and alkylation of quinoxalin-2(1H)-ones and quinolines. This catalyst-free process utilizes air as the oxidant, offering mild reaction conditions, environmental sustainability, and broad functional group compatibility. The approach enables the synthesis of aryl and alkyl derivatives of quinoxalin-2(1H)-ones and quinolines with high to excellent yields. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic and age-related lung disease that has few treatment options. Reactive oxygen species (ROS) play an important role in the introduction and development of IPF. In the present study, we developed multifunctional Cobalt (Co)–Manganese (Mn) complex oxide nanoparticles (Co-MnNPs), which can scavenge multiple types of ROS. Benefiting from ROS scavenging activities and good biosafety, Co-MnNPs can suppress canonical and non-canonical TGF-β pathways and, thus, inhibit the activation of fibroblasts and the productions of extracellular matrix. Furthermore, the scavenging of ROS by Co-MnNPs reduce the LPS-induced expressions of pro-inflammatory factors in macrophages, by suppressing NF-κB signaling pathway. Therefore, Co-MnNPs can reduce the excessive extracellular matrix deposition and inflammatory responses in lungs and, thus, alleviate pulmonary fibrosis induced by bleomycin (BLM) in mice. Taken together, this work offers an anti-fibrotic agent for treatment of IPF and other ROS-related diseases. [ABSTRACT FROM AUTHOR]

1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) is the main phenolic active ingredient in Paeoniae Radix Alba, which is commonly used for the treatment of osteoporosis (OP). PGG is a potent natural antioxidant, and its effects on OP remain unknown. This study aimed to investigate the effects of PGG on promoting bone formation and explore its estrogen receptor (ER)-related mechanisms. A hydrogen peroxide-induced osteoblast apoptosis model was established in MC3T3-E1 cells. The effects of PGG were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, alkaline phosphatase (ALP) staining, RT-qPCR, and Western blot methods. Furthermore, a prednisolone-induced zebrafish OP model was employed to study the effects in vivo. ER inhibitors and molecular docking methods were used further to investigate the interactions between PGG and ERs. The results showed that PGG significantly enhanced cell viability and decreased cell apoptosis by restoring mitochondrial function, attenuating reactive oxygen species levels, decreasing the mitochondrial membrane potential, and enhancing ATP production. PGG enhanced ALP expression and activity and elevated osteogenic differentiation. PGG also promoted bone formation in the zebrafish model, and these effects were reversed by ICI182780. These results provide evidence that the effects of PGG in alleviating apoptosis and promoting bone formation may depend on ERs. As such, PGG is considered a valuable candidate for treating OP. [ABSTRACT FROM AUTHOR]

Guanine-quadruplex (G4) selective photosensitizers have huge potential for photodynamic therapy against various diseases correlated with G4 DNA and G4 RNAs; however, the types of photosensitizer skeletons available are limited. Herein, we investigated the ability of our original G4 ligands, tripodal quinone-cyanine dyes (tpQCy(s)), which were developed as fluorescent probes for G4, to act as photosensitizers for cancer-selective apoptosis inducers. The results indicated that the tpQCy skeleton has great potential for developing G4-targeted cancer-selective photosensitizers for photodynamic therapy. Among the two tpQCys, only QCy(BnBT)3, which has greater G4 selectivity, exhibited photoinduced cytotoxicity in HeLa cell growth, suggesting that the direct oxidation of G4 DNA or RNA is crucial for photoinduced cytotoxicity. RNA-seq analysis using a next-generation sequencing technique revealed that apoptosis was clearly induced by photoirradiation after QCy(BnBT)3 treatment. [ABSTRACT FROM AUTHOR]

Depression is a complex and common mental illness affecting physical and psychological health. Panax ginseng C. A. Mey is a traditional Chinese medicine with abundant pharmacological activity and applications in regulating mood disorders. 20 (S)-Protopanaxadiol is the major intestinal metabolite of ginsenoside and one of the active components in ginseng. In this study, we aimed to investigate the therapeutic effects of 20 (S)-Protopanaxadiol on neuronal damage and depression, which may involve mitochondrial dynamics. However, the mechanism underlying the antidepressant effects of 20 (S)-Protopanaxadiol is unelucidated. In the present study, we investigated the potential mechanisms underlying the antidepressant activity of 20 (S)-Protopanaxadiol by employing a corticosterone-induced HT22 cellular model and a chronic unpredicted mild stress (CUMS)-induced animal model in combination with a network pharmacology approach. In vitro, the results showed that 20 (S)-Protopanaxadiol ameliorated the corticosterone (CORT)-induced decrease in HT22 cell viability, decrease in 5-hydroxytryptamine (5-HT) levels, and increase in nitric oxide (NO) and malondialdehyde (MDA) levels. Furthermore, 20 (S)-Protopanaxadiol exerted improvement effects on the CORT-induced increase in HT22 cell mitochondrial reactive oxygen species, loss of mitochondrial membrane potential, and apoptosis. In vivo, the results showed that 20 (S)-Protopanaxadiol ameliorated depressive symptoms and hippocampal neuronal damage in CUMS mice, and sirtuin1 (SIRT1) and peroxisome proliferator-activated receptor-1-Alpha (PGC-1α) activity were activated in the hippocampus of mice, thereby alleviating mitochondrial dysfunction and promoting the clearance of damaged mitochondria. In both in vivo and in vitro models, after inhibiting SIRT1 expression, the protective effect of 20 (S)-Protopanaxadiol on mitochondria was significantly weakened, and dynamin-related protein 1 (DRP1)-mediated mitochondrial division was significantly reduced. These findings suggest that 20 (S)-Protopanaxadiol may exert neuroprotective and antidepressant effects by attenuating DRP1-mediated mitochondrial dysfunction and apoptosis by modulating the SIRT1/PGC-1α signaling pathway. [ABSTRACT FROM AUTHOR]

Neuroinflammation that is caused by microglia, the main immune cells of the brain, contributes to neurodegenerative diseases. Psychedelics, including psilocybin and lysergic acid diethylamide (LSD), possess certain anti-inflammatory properties and, therefore, should be considered as drug candidates for treating neuroinflammatory pathologies. When ingested, psilocybin is rapidly dephosphorylated to yield psilocin, which crosses the blood–brain barrier and exerts psychotropic activity by interacting with the 5-hydroxytryptamine 2A receptors (5-HT2ARs) on neurons. Since microglia express all three 5-HT2R isoforms, we hypothesized that, by interacting with these receptors, psilocin beneficially modulates select neuroimmune functions of microglia. We used microglia-like cell lines to demonstrate that psilocin, at non-toxic concentrations, did not affect the secretion of tumor necrosis factor (TNF) by immune-stimulated microglial cells, but significantly inhibited their phagocytic activity, the release of reactive oxygen species (ROS), and nitric oxide (NO) production. The inhibitory activity of psilocin on the latter two functions was similar to that of two selective 5-HT2R agonists, namely, 25I-NBOH and Ro60-0175. The role of this subfamily of receptors was further demonstrated by the application of 5-HT2R antagonists cyproheptadine and risperidone. Psilocin should be considered a novel drug candidate that might be effective in treating neuroimmune disorders, such as neurodegenerative diseases, where reactive microglia are significant contributors. [ABSTRACT FROM AUTHOR]

During their life cycle, plants constantly respond to environmental changes. Abiotic stressors affect the photosynthetic and respiratory processes of plants. Reactive oxygen species (ROS) are produced during aerobic metabolism and play an important role as regulatory mediators in signaling processes, activating the plant's protective response to abiotic stress and restoring "oxidation-reduction homeostasis". Cells develop normally if the rates of ROS production and the ability to neutralize them are balanced. To implement oxidation-reduction signaling, this balance must be disrupted either by an increase in ROS concentration or a decrease in the activity of one or more antioxidant systems. Under abiotic stress, plants accumulate excessive amounts of ROS, and if the ROS content exceeds the threshold amount dangerous for living organisms, it can lead to damage to all major cellular components. Adaptive resistance of plants to abiotic stressors depends on a set of mechanisms of adaptation to them. The accumulation of ROS in the cell depends on the type of abiotic stress, the strength of its impact on the plant, the duration of its impact, and the recovery period. The aim of this review is to provide a general understanding of the processes occurring during ROS homeostasis in plants, oxidation-reduction processes in cellular compartments in response to abiotic stress, and the participation of ROS in signaling processes activating adaptation processes to abiotic stress. [ABSTRACT FROM AUTHOR]

Stress in birds disrupts the homeostasis of the organism, leading to an inability to neutralize reactive oxygen species. Taurine, an effective antioxidant, affects various cellular mechanisms, including cation modulation, protein phosphorylation, and cell proliferation. The aim of the study was to evaluate the effect of colloid with taurine applied in ovo to Albumin on embryonic development, oxidative stress indicators and the content of bioactive peptides—carnosine and anserine—in the pectoral muscle. The research materials were eggs of the parent flock (Ross 308) divided into four groups (K (without injection), T50-concentration of taurine hydrocolloid 50 ppm (mg/L); T100-colloid concentration 100 ppm (mg/L) taurine; T500-colloid concentration of 500 ppm (mg/L) taurine). The experimental solutions were injected in an amount of 0.3 mL into egg white. Eggs were incubated under standard incubation conditions. The addition of 100 and 500 ppm taurine had a highly significant (p = 0.001) effect on the plasma antioxidant potential in chicks. The level of anserine increased with increasing concentrations of taurine. These changes were highly significant (p = 0.007). The level of anserine in the T2 and T3 groups was determined to be 2.5 times higher than in the pectoral muscles of embryos not treated with taurine colloid. An analysis of the results showed that the administration of an increased dose of hydrocolloid with taurine increased the content of carnosine and anserine in the pectoral muscle. Colloid with taurine applied in ovo to chicken white egg reduces oxidative stress and increases homeostasis of the organism. [ABSTRACT FROM AUTHOR]

Ferroptosis is a regulated cell death process characterized by iron ion catalysis and reactive oxygen species, leading to lipid peroxidation. This mechanism plays a crucial role in age-related diseases, including cancer and cardiovascular and neurological disorders. To better mimic iron-induced cell death, predict the effects of various elements, and identify drugs capable of regulating ferroptosis, it is essential to develop precise models of this process. Such drugs can be tested on cellular models. Systems biology offers a powerful approach to studying biological processes through modeling, which involves accumulating and analyzing comprehensive research data. Once a model is created, it allows for examining the system's response to various stimuli. Our goal is to develop a modular framework for ferroptosis, enabling the prediction and screening of compounds with geroprotective and antiferroptotic effects. For modeling and analysis, we utilized BioUML (Biological Universal Modeling Language), which supports key standards in systems biology, modular and visual modeling, rapid simulation, parameter estimation, and a variety of numerical methods. This combination fulfills the requirements for modeling complex biological systems. The integrated modular model was validated on diverse datasets, including original experimental data. This framework encompasses essential molecular genetic processes such as the Fenton reaction, iron metabolism, lipid synthesis, and the antioxidant system. We identified structural relationships between molecular agents within each module and compared them to our proposed system for regulating the initiation and progression of ferroptosis. Our research highlights that no current models comprehensively cover all regulatory mechanisms of ferroptosis. By integrating data on ferroptosis modules into an integrated modular model, we can enhance our understanding of its mechanisms and assist in the discovery of new treatment targets for age-related diseases. A computational model of ferroptosis was developed based on a modular modeling approach and included 73 differential equations and 93 species. [ABSTRACT FROM AUTHOR]

Heterogeneous Mg-Fe oxide/biochar (MgFeO@BC) nanocomposites were synthesized by a co-precipitation method and used as biochar-based catalysts to activate peroxymonosulfate (PMS) for sulfamethoxazole (SMX) removal. The optimal conditions for SMX degradation were examined as follows: pH 7.0, MgFeO@BC of 0.4 g/L, PMS concentration of 0.6 mM and SMX concentration of 10.0 mg/L at 25 ℃. In the MgFeO@BC/PMS system, the removal efficiency of SMX was 99.0% in water within 40 min under optimal conditions. In the MgFeO@BC/PMS system, the removal efficiencies of tetracycline (TC), cephalexin (CEX), ciprofloxacin (CIP), 4-chloro-3-methyl phenol (CMP) and SMX within 40 min are 95.3%, 98.4%, 98.2%, 97.5% and 99.0%, respectively. The radical quenching experiments and electron spin resonance (ESR) analysis suggested that both non-radical pathway and radical pathway advanced SMX degradation. SMX was oxidized by sulfate radicals (SO4•−), hydroxyl radicals (•OH) and singlet oxygen (1O2), and SO4•− acted as the main active species. MgFeO@BC exhibits a higher current density, and therefore, a higher electron migration rate and redox capacity. Due to the large number of available binding sites on the surface of MgFeO@BC and the low amount of ion leaching during the catalytic reaction, the system has good anti-interference ability and stability. Finally, the intermediates of SMX were detected. [ABSTRACT FROM AUTHOR]

Melatonin treatment has been reported to effectively preserve and improve the postharvest quality of fruits and vegetables during storage. This research focused on examining the significance of melatonin on maintaining the quality of fresh Gastrodia elata tubers throughout the storage period. The findings demonstrated that melatonin application effectively reduced the deterioration rate and inhibited the rise in respiratory rate, malondialdehyde content, and weight loss, while slowing down the decline in soluble solid content. Melatonin treatment led to a decrease in hydrogen peroxide production and a rise in non-enzymatic antioxidant concentrations, including ascorbic acid. Furthermore, it boosted both the activity and expression of indispensable antioxidant enzymes, like superoxide dismutase, catalase, and ascorbate peroxidase. Additionally, melatonin treatment promoted the accumulation of total phenols, flavonoids, and lignin in fresh G. elata, while enhancing both the activity and expression of critical enzymes in the phenylpropanoid pathway, including phenylalanine ammonia-lyase, cinnamate-4-hydroxylase, and 4-coumarate-CoA ligase. Moreover, melatonin treatment boosted the activity and expression of energy-associated enzymes including H+-ATPase, succinate dehydrogenase, Ca2+-ATPase, and cytochrome C oxidase, contributing to the improvement of energy levels in fresh G. elata. In summary, melatonin enhances the antioxidant potential and reduces oxidative damage in fresh G. elata by activating reactive oxygen species, phenylpropanoid metabolism, and energy metabolism, thereby maintaining its postharvest quality. [ABSTRACT FROM AUTHOR]

Revascularization procedures such as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are crucial to restore blood flow to the heart and are used in the treatment of myocardial infarction (MI). However, these techniques are known to cause myocardial reperfusion injury in the ischemic heart. The present study aims to mimic ischemia–reperfusion injury in vitro on primary human cardiomyocytes (HCMs) and use the established injury model to study the rescue mechanism of skeletal muscle cell (SkM)-seeded electrospun fiber-coated human amniotic membrane scaffold (EF–HAM) on injured cardiomyocytes through paracrine secretion. An in vitro ischemia–reperfusion injury model was established by exposing the HCM to 5 h of hypoxia, followed by a 6 h reoxygenation period. Six different conditioned media (CM) including three derived from SkM-seeded EF–HAMs were introduced to the injured cells to investigate the cardioprotective effect of the CM. Cell survival analysis, caspase-3 and XIAP expression profiling, mitochondrial membrane potential analysis, and measurement of reactive oxygen species (ROS) were conducted to evaluate the outcomes of the study. The results revealed a significant increase in the viability of HCM exposed to H/R injury by 77.2% (p < 0.01), 111.8% (p < 0.001), 68.7% (p < 0.05), and 69.5% (p < 0.05) when supplemented with HAM CM, EF–HAM 3 min CM, EF–HAM 5 min CM, and EF–HAM 7 min CM, respectively. Furthermore, CM derived from SkM-seeded EF–HAM scaffolds positively impacted hypoxia-/reoxygenation-induced changes in caspase-3 expression, mitochondrial membrane potential, and reactive oxygen species generation, but not in XIAP expression. These findings suggest that EF–HAM composite scaffolds can exert antiapoptotic and cardioregenerative effects on primary human cardiomyocytes through the paracrine mechanism. [ABSTRACT FROM AUTHOR]

The therapeutic potential of redox-active nanoscale materials as antioxidant- or reactive oxygen species (ROS)-inducing agents was intensely studied. Herein, we demonstrate that the synthesized and characterized GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles, which have been already shown to have redox-active, anti-inflammatory, antibacterial, and wound healing properties, both in vitro and in vivo, worsen oxidative stress of L929 cells triggered by hydrogen peroxide or tert-butyl hydroperoxide (tBuOOH) at the concentrations that are safe for intact L929 cells. This effect was observed upon internalization of the investigated nanosized materials and is associated with the cleavage of caspase-3 and caspase-9 without recruitment of caspase-8. Such changes in the caspase cascade indicate activation of the intrinsic caspase-9-dependent mitochondrial but not the extrinsic death, receptor-mediated, and caspase-8-dependent apoptotic pathway. The GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticle-induced apoptosis of oxidatively compromised L929 cells is mediated by ROS overgeneration, Ca2+ overload, endoplasmic reticulum stress-associated JNK (c-Jun N-terminal kinase), and DNA damage-inducible transcript 3 (DDIT3). Our findings demonstrate that GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles aggravate the oxidative stress-induced damage to L929 cells, indicating that they might potentially be applied as anti-cancer agents. [ABSTRACT FROM AUTHOR]

Irradiation of the head and neck inevitably leads to decreased salivary gland function. It is postulated that radiation generates excessive reactive oxygen species (ROS) and reduces salivary gland function by ferroptosis, a new cell death mechanism; however, research in this area is currently lacking. In this study, we investigated the effects of amifostine and melatonin on acute salivary gland dysfunction and ferroptosis. Thirty-two Sprague Dawley rats were divided into four groups: control, radiation, radiation + amifostine, and radiation + melatonin. ROS; iron levels; glutathione peroxidase 4; 4-hydroxynonenal; various cytokines; and fibrosis and salivary gland functional markers were measured. Western blotting was used to detect ferritinophagy. After irradiation, we observed an increase in iron levels, ROS generation, oxidized glutathione, lipid peroxidation, fibrosis, and salivary gland dysfunction and a decrease in glutathione peroxidase 4 in salivary gland tissue. Treatment with amifostine or melatonin decreased the ferroptotic response and improved acute salivary gland function 10 days after radiation. The increase in iron levels associated with ferritinophagy was reduced after treatment with amifostine or melatonin. Our results demonstrate that radiation-induced acute salivary gland dysfunction is associated with ferroptosis and ferritinophagy. Amifostine and melatonin inhibit radiation-induced ferroptosis and ferritinophagy in the salivary gland and prevent acute salivary gland dysfunction 10 days after radiation. [ABSTRACT FROM AUTHOR]

The crosstalk between tumor progression and ferroptosis is largely unknown. Here, we identify malate dehydrogenase 2 (MDH2) as a key regulator of ferroptosis. MDH2 deficiency inhibits the growth of hepatocellular carcinoma (HCC) cells and enhances their sensitivity to ferroptosis induced by RAS-selective lethal 3 (RSL3), a compound known to cause ferroptosis. MDH2 knock-down enhances RSL3-induced intracellular reactive oxygen species, free iron ions and lipid per-oxides levels, leading to HCC ferroptotic cell death which is rescued by ferrostatin-1 and iron chelator deferiprone. Importantly, the inhibition of HCC cell growth caused by MDH2 deficiency is partially rescued by ferroptosis blockade. Mechanistically, MDH2 resists RSL3-induced ferroptosis sensitivity dependent on glutathione peroxidase 4 (GPX4), an enzyme responsible for scavenging lipid peroxides, which is stabilized by MDH2 in HCC. The protein expressions of MDH2 and GPX4 are positively correlated with each other in HCC cell lines. Furthermore, through our UALCAN website analysis, we found that MDH2 and GPX4 are highly expressed in HCC samples. These findings reveal a critical mechanism by which HCC evades ferroptosis via MDH2-mediated stabilization of GPX4 to promote tumor progression and underscore the potential of MDH2 inhibition in combi-nation with ferroptosis inducers for the treatment of HCC. [ABSTRACT FROM AUTHOR]

This review explores the regenerative capacity of Xenopus laevis, focusing on tail regeneration, as a model to uncover cellular, molecular, and developmental mechanisms underlying tissue repair. X. laevis tadpoles provide unique insights into regenerative biology due to their regeneration-competent and -incompetent stages and ability to regrow complex structures in the tail, including the spinal cord, muscle, and skin, after amputation. The review delves into the roles of key signaling pathways, such as those involving reactive oxygen species (ROS) and signaling molecules like BMPs and FGFs, in orchestrating cellular responses during regeneration. It also examines how mechanotransduction, epigenetic regulation, and metabolic shifts influence tissue restoration. Comparisons of regenerative capacity with other species shed light on the evolutionary loss of regenerative abilities and underscore X. laevis as an invaluable model for understanding the constraints of tissue repair in higher organisms. This comprehensive review synthesizes recent findings, suggesting future directions for exploring regeneration mechanisms, with potential implications for advancing regenerative medicine. [ABSTRACT FROM AUTHOR]

Inflammation is a major component of the pathogenesis of atherosclerosis and the formation of in-stent restenosis (ISR). A novel flavonoid, DHIF, attenuates reactive oxygen species and nf-κB signaling and has potential to limit ISR via antioxidant action. While current drug eluting stents (DESs) perform well in clinical practice, new therapies to prevent ISR without dependance on cytotoxic drugs are warranted. Our objective was to test whether DHIF reduces ISR in a hyperlipidemic rabbit aorta model of ISR via attenuated inflammatory responses. WHHL rabbit aortas (n = 24) were denuded. Six weeks after injury, stents were implanted into the denuded aortas. DHIF was dissolved in carboxymethyl cellulose (CMC) and administered orally with two doses. CMC served as a control. The animals were sacrificed six weeks after stenting. ISR was evaluated from stent histomorphometry and immunohistology was used to assess the inflammatory and antiproliferative effects of the treatment. ISR was reduced from 20.9 ± 3.0% in controls to 15.2 ± 2.4% (p = 0.0009) and 16.4 ± 2.1% (p = 0.004) in the low- and high-dose groups, respectively. The neointimal area covered by macrophages was 32 ± 9.3% in the controls, 17.2 ± 5.9% (p = 0.005) in the low-dose group and 19.4 ± 7.9% (p = 0.008) in the high-dose group. DHIF significantly reduces ISR and local inflammation in stented arterial regions and could be used to reduce ISR when bare metal stents are used. Targeting local inflammation in the arterial wall may provide a way to reduce ISR in a clinical setting and further studies are warranted. [ABSTRACT FROM AUTHOR]

Equine recurrent uveitis (ERU) is a spontaneously occurring autoimmune disease and one of the leading causes of blindness in horses worldwide. Its similarities to autoimmune-mediated uveitis in humans make it a unique spontaneous animal model for this disease. Although many aspects of ERU pathogenesis have been elucidated, it remains not fully understood and requires further research. CD4+ T cells have been a particular focus of research. In a previous study, we showed metabolic alterations in CD4+ T cells from ERU cases, including an increased basal oxygen consumption rate (OCR) and elevated compensatory glycolysis. To further investigate the underlying reasons for and consequences of these metabolic changes, we quantified reactive oxygen species (ROS) production in CD4+ T cells from ERU cases and compared it to healthy controls, revealing significantly higher ROS production in ERU-affected horses. Additionally, we aimed to define mitochondrial fuel oxidation of glucose, glutamine, and long-chain fatty acids (LCFAs) and identified significant differences between CD4+ T cells from ERU cases and controls. CD4+ T cells from ERU cases showed a lower dependency on mitochondrial glucose oxidation and greater metabolic flexibility for the mitochondrial oxidation of glucose and LCFAs, indicating an enhanced ability to switch to alternative fuels when necessary. [ABSTRACT FROM AUTHOR]

Rice phosphatidylcholine transfer protein (PCTP), which contains a steroidogenic acute regulatory protein-related lipid transfer (START) domain, responds to bacterial blight disease. Overexpression of OsPCTP quantitatively enhances resistance to pathogen in rice, whereas depletion of it has the opposite effect. Further analysis showed that OsPCTP physically interacts with OsAPX8, a ROS scavenging enzyme, and influences ascorbate peroxidase enzymatic activity in vivo. In addition, the expression of pathogenesis-related genes PR1a, PR1b and PR10 were significantly induced in OsPCTP-OE plants compared with that in wild-type plants ZH11. Taken together, these results suggested that OsPCTP mediates bacterial blight resistance in rice through regulating the ROS defense pathway. [ABSTRACT FROM AUTHOR]

Breast cancer is a public health concern worldwide, characterized by increasing incidence and mortality rates, requiring novel and effective therapeutic strategies. Curcumin is a bioactive compound extracted from turmeric with several pharmacological activities. Curcumin is a multifaceted anticancer agent through mechanisms including the modulation of signaling pathways, inhibition of cell proliferation, induction of apoptosis, and production of reactive oxygen species. However, the poor water solubility and bioavailability of curcumin create important barriers in its clinical application. This review elaborates on the therapeutic potential of curcumin in breast cancer treatment, focusing on the efficacy of different administration routes and synergistic effects with other therapeutic agents. The intravenous administration of curcumin-loaded nanoparticles significantly improves bioavailability and therapeutic outcomes compared to oral routes. Innovative formulations, such as nano-emulsifying drug delivery systems, have shown promise in enhancing oral bioavailability. While intravenous delivery ensures higher bioavailability and direct action on tumor cells, it is more invasive and expensive than oral administration. Advancing research on curcumin in breast cancer treatment is essential for improving therapeutic outcomes and enhancing the quality of life of patients. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) toxicity causes oxidative stress damage in plant cells. Glutaredoxins (GRXs), a type of small oxidoreductase, play a crucial role in modulating thiol redox states. However, whether GRXs act in Cd stress remains to be identified. Here, we reveal that Arabidopsis GRX480, a member of the CC-type family, enhances plant Cd stress tolerance. The GRX480 mutants exhibit enhanced sensitivity to Cd stress, manifested by shortened root, reduced biomass, lower chlorophyll and proline levels, and decreased photosynthetic efficiency compared with the wild type. The Cd concentration in GRX480 mutants is higher than the wild type, resulting from the inhibition of Cd efflux and transport genes transcription. Lower levels of GSH were detected in Cd-treated GRX480 mutants than in the wild type, indicating that GRX480 regulates plant Cd tolerance by influencing the balance between GSH and GSSG. Furthermore, the hyperaccumulation of reactive oxygen species (ROS) is associated with decreased expression of H2O2 scavenging genes in Cd-treated GRX480 mutants. Additionally, more toxic reactive carbonyl species (RCS), produced during oxidative stress, accumulate in Cd-treated GRX480 mutants than in wild type. Overall, our study establishes a critical role of GRX480 in response to Cd stress, highlighting its multifaceted contributions to detoxification and the maintenance of redox homeostasis. [ABSTRACT FROM AUTHOR]

Cisplatin-induced ototoxicity occurs in approximately half of patients treated with cisplatin, and pediatric patients are more likely to be affected than adults. The oxidative stress elicited by cisplatin is a key contributor to the pathogenesis of ototoxicity. Notoginsenoside R1 (NGR1), the main bioactive compound of Panax notoginseng saponins, has antioxidant and antiapoptotic effects. This study investigated the ability of NGR1 to protect against cisplatin-induced damage in auditory HEI-OC1 cells and neonatal murine cochlear explants. The viability of HEI-OC1 cells treated with NGR1 and cisplatin was greater than that of cells treated with cisplatin alone. The results of Western blots and immunostaining for cleaved caspase-3 revealed that the level of cleaved caspase-3 in the cells treated with cisplatin was repressed by NGR1. NGR1 attenuated cisplatin-induced cytotoxicity in HEI-OC1 cells. Intracellular reactive oxygen species (ROS) were detected with a DCFDA assay and immunostaining for 4-HNE. The result revealed that its expression was induced by cisplatin and was significantly reduced by NGR1. Moreover, NGR1 can promote heme oxygenase-1 (HO-1) expression at both the mRNA and protein levels. ZNPPIX, an HO-1 inhibitor, was administered to cisplatin-treated cells to investigate the role of HO-1 in the protective effect of NGR1. The suppression of HO-1 activity by ZNPPIX markedly abolished the protective effect of NGR1 on cisplatin-treated cells. Therefore, NGR1 protects cells from cisplatin-induced damage by activating HO-1 and its antioxidative activity. In cochlear explants, NGR1 protects cochlear hair cells and attenuates cisplatin-induced ototoxicity by inhibiting ROS generation. In the group treated with cisplatin alone, prominent loss of outer hair cells and severe damage to the structure of the stereociliary bundles of inner and outer hair cells were observed. Compared with the group treated with cisplatin alone, less loss of outer hair cells (p = 0.009) and better preservation of the stereociliary bundles of hair cells were observed in the group treated with cisplatin and NGR1. In conclusion, these findings indicate that NGR1 can protect against cisplatin-induced ototoxicity by inducing HO-1 expression and suppressing oxidative stress. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is marked by a progressive loss of central vision and is the third leading cause of irreversible blindness worldwide. The exact mechanisms driving the progression of this macular degenerative condition remain elusive, and as of now, there are no available preventative measures for dry AMD. According to ancient records, ginseng affects the eyes by brightening them and enhancing wisdom. Modern pharmacological research shows that the active ingredients in ginseng, ginsenosides, may be used to prevent or improve eye diseases that threaten vision. Some articles have reported that ginsenoside Rg3 can treat diabetic retinopathy in mice, but no reports exist on its effects and mechanisms in AMD. Therefore, the role and mechanism of ginsenoside Rg3 in AMD warrant further study. This study aims to investigate the effects of Rg3 on AMD and its underlying molecular mechanisms. We established a mouse model of AMD to examine the impact of ginsenoside Rg3 on NaIO3-induced apoptosis in the retina and to explore the related intrinsic mechanisms. The in vivo results indicated that ginsenoside Rg3 prevents NaIO3-induced apoptosis in retinal pigment epithelial cells by inhibiting reactive oxygen species production and preventing the reduction in mitochondrial membrane potential. Additionally, we assessed the levels of protein expression within the apoptosis pathway. Ginsenoside Rg3 decreased the expression of Bax, cleaved caspase-3, and cleaved caspase-9 proteins. Additionally, it increased the expression of Bcl-2 by decreasing P-JNK levels. Moreover, our in vivo results showed that ginsenoside Rg3 enhanced retinal structure, increased the relative thickness of the retina, and decreased the extent of disorganization in both the inner and outer nuclear layers. Ginsenoside Rg3 may safeguard the retina against NaIO3-induced cell apoptosis by attenuating reactive-oxygen-species-mediated mitochondrial dysfunction, in which the JNK signaling pathway is also involved. These findings suggest that ginsenoside Rg3 has the potential to prevent or attenuate the progression of AMD and other retinal pathologies associated with NaIO3-mediated apoptosis. [ABSTRACT FROM AUTHOR]

Retinoic-acid-related orphan receptors (RORs) are transcription factors belonging to the nuclear receptor subfamily consisting of RORα, RORβ, and RORγ. By binding to the ROR response elements (ROREs) on target gene promoters, RORs regulate a wide variety of cellular processes, including autophagy, mitophagy, oxidative stress, and inflammation. The regulatory roles of RORs are observed in cardiac cells, hepatocytes, pulmonary epithelial cells, renal cells, immune cells, and cancer cells. A growing body of clinical and experimental evidence suggests that ROR expression levels are markedly reduced under different pathological and stress conditions, suggesting that RORs may play a critical role in the pathogenesis of a variety of disease states, including myocardial infarction, immune disorders, cancer, and metabolic syndrome. Reductions in RORs are also associated with inhibition of autophagy, increased reactive oxygen species (ROS), and increased cell death, underscoring the importance of RORs in the regulation of these processes. Herein, we highlight the relationship between RORs and homeostatic processes that influence cell viability. Understanding how these intricate processes are governed at the cellular level is of high scientific and clinical importance to develop new therapeutic strategies that modulate ROR expression and disease progression. [ABSTRACT FROM AUTHOR]

The wound repair process usually leads to a non-functioning mass of fibrotic tissue because of the oxidative imbalance of deep tissue layers. However, how to improve the penetration of active ingredients into deeper layers and regulate oxidative imbalances to create a regenerative microenvironment still remains a challenge. In this study, we designed a novel tetrahedral-framework nucleic acid (tFNA) nanozyme that could penetrate the skin/mucosa barrier as deep as 450 μm within 24 h. We also demonstrated the protective role of tFNAs on the mitochondrial structural and functional integrity and inhibition of reactive oxygen species production to repair oxidative imbalances through ERK1/2-Nrf2-HO-1 during repair processes. It was found that the proliferative state and the migration ability of postburn cells in vitro were accelerated, and the early closure of wounds in vivo was significantly promoted. This study therefore provides a promising strategy to efficiently regulate the oxidative imbalances in the deep layers of the skin during wound healing. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and its prevention and treatment face severe challenges. It is crucial to improve the targeting of drugs on tumor cells and tissues. Celastrol (CeT), as an active ingredient of traditional Chinese medicine, possesses strong antitumor effects, especially in triggering apoptosis of HCC. However, due to its toxicity and lack of targeting, its application is greatly limited. HMCLPs, a nano-biomimetic platform carrying CeT with controllable drug release, enhanced targeting, and immunocompatibility, were developed for the first time, which can be used for the treatment of HCC. By utilizing homologous cell membranes and hyaluronic acid (HA), HMCLPs can precisely target tumor regions and release CeT in a controlled manner. Both in vitro and in vivo studies have demonstrated that HMCLPs loaded with CeT significantly increased the accumulation of reactive oxygen species (ROS), induced mitochondrial damage, and triggered apoptosis of HCC cells, resulting in effective treatment with minimal adverse reaction. The development of HMCLPs as a nanocarrier system for CeT delivery offers a promising therapeutic strategy for HCC. This innovative approach improves the targeted delivery and bioavailability of CeT, dramatically induces apoptosis in HCC cells, and exerts its powerful antitumor effects while minimizing systemic toxicity. The present study highlights the potential of combining innovative nanocarriers with powerful natural compounds such as CeT to enhance efficacy and reduce toxicity. [ABSTRACT FROM AUTHOR]

Red blood cells respond to fluctuations in blood plasma pH by changing the rate of biochemical and physical processes that affect the specific functions of individual cells. This study aimed to analyze the effect of pH changes on red blood cell morphology and structure. The findings revealed that an increase or decrease in pH above or below the physiological level of pH 7.4 results in the transformation of discocytes into echinocytes and causes significant alterations in the membrane, including its roughness, cytoskeleton structure, and the cell's elastic modulus. Furthermore, the study shown a strong connection between critical acidosis and alkalosis with increased intracellular reactive oxygen species production. [ABSTRACT FROM AUTHOR]

Pulmonary artery endothelial cells (PAECs) are a major contributor to hypoxic pulmonary hypertension (PH) due to the possible roles of reactive oxygen species (ROS). However, the molecular mechanisms and functional roles of ROS in PAECs are not well established. In this study, we first used Amplex UltraRed reagent to assess hydrogen peroxide (H2O2) generation. The result indicated that hypoxic exposure resulted in a significant increase in Amplex UltraRed-derived fluorescence (i.e., H2O2 production) in human PAECs. To complement this result, we employed lucigenin as a probe to detect superoxide (O2−) production. Our assays showed that hypoxia largely increased O2− production. Hypoxia also enhanced H2O2 production in the mitochondria from PAECs. Using the genetically encoded H2O2 sensor HyPer, we further revealed the hypoxic ROS production in PAECs, which was fully blocked by the mitochondrial inhibitor rotenone or myxothiazol. Interestingly, hypoxia caused an increase in the migration of PAECs, determined by scratch wound assay. In contrast, nicotine, a major cigarette or e-cigarette component, had no effect. Moreover, hypoxia and nicotine co-exposure further increased migration. Transfection of lentiviral shRNAs specific for the mitochondrial Rieske iron–sulfur protein (RISP), which knocked down its expression and associated ROS generation, inhibited the hypoxic migration of PAECs. Hypoxia largely increased the proliferation of PAECs, determined using Ki67 staining and direct cell number accounting. Similarly, nicotine caused a large increase in proliferation. Moreover, hypoxia/nicotine co-exposure elicited a further increase in cell proliferation. RISP knockdown inhibited the proliferation of PAECs following hypoxia, nicotine exposure, and hypoxia/nicotine co-exposure. Taken together, our data demonstrate that hypoxia increases RISP-mediated mitochondrial ROS production, migration, and proliferation in human PAECs; nicotine has no effect on migration, increases proliferation, and promotes hypoxic proliferation; the effects of nicotine are largely mediated by RISP-dependent mitochondrial ROS signaling. Conceivably, PAECs may contribute to PH via the RISP-mediated mitochondrial ROS. [ABSTRACT FROM AUTHOR]

Viruses are intracellular parasites that utilize organelles, signaling pathways, and the bioenergetics machinery of the cell to replicate the genome and synthesize proteins to build up new viral particles. Mitochondria are key to supporting the virus life cycle by sustaining energy production, metabolism, and synthesis of macromolecules. Mitochondria also contribute to the antiviral innate immune response. Here, we describe the different mechanisms involved in virus–mitochondria interactions. We analyze the effects of viral infections on the metabolism of glucose in the Warburg phenotype, glutamine, and fatty acids. We also describe how viruses directly regulate mitochondrial function through modulation of the activity of the electron transport chain, the generation of reactive oxygen species, the balance between fission and fusion, and the regulation of voltage-dependent anion channels. In addition, we discuss the evasion strategies used to avoid mitochondrial-associated mechanisms that inhibit viral replication. Overall, this review aims to provide a comprehensive view of how viruses modulate mitochondrial function to maintain their replicative capabilities. [ABSTRACT FROM AUTHOR]

Microplastics and nanoplastics (MNPs) are ubiquitous environmental contaminants. Their prevalence, persistence, and increasing industrial production have led to questions about their long-term impact on human and animal health. This narrative review describes the effects of MNPs on oxidative stress, inflammation, and aging. Exposure to MNPs leads to increased production of reactive oxygen species (ROS) across multiple experimental models, including cell lines, organoids, and animal systems. ROS can cause damage to cellular macromolecules such as DNA, proteins, and lipids. Direct interaction between MNPs and immune cells or an indirect result of oxidative stress-mediated cellular damage may lead to increased production of pro-inflammatory cytokines throughout different MNP-exposure conditions. This inflammatory response is a common feature in the pathogenesis of neurodegenerative, cardiovascular, and other age-related diseases. MNPs also act as cell senescence inducers by promoting mitochondrial dysfunction, impairing autophagy, and activating DNA damage responses, exacerbating cellular aging altogether. Increased senescence of reproductive cells and transfer of MNPs/induced damages from parents to offspring in animals further corroborates the transgenerational health risks of the tiny particles. This review aims to provoke a deeper investigation into the notorious effects these pervasive particles may have on human well-being and longevity. [ABSTRACT FROM AUTHOR]

From quiescence to activation and myogenic differentiation, muscle stem cells (MuSCs) experience drastic alterations in their signaling activity and metabolism. Through balanced cycles of fission and fusion, mitochondria alter their morphology and metabolism, allowing them to affect their decisive role in modulating MuSC activity and fate decisions. This tightly regulated process contributes to MuSC regulation by mediating changes in redox signaling pathways, cell cycle progression, and cell fate decisions. In this review, we discuss the role of mitochondrial dynamics as an integral modulator of MuSC activity, fate, and maintenance. Understanding the influence of mitochondrial dynamics in MuSCs in health and disease will further the development of therapeutics that support MuSC integrity and thus may aid in restoring the regenerative capacity of skeletal muscle. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) infection is characterized by febrile illness, severe joint pain, myalgia, and cardiovascular complications. Given that CHIKV stimulates reactive oxygen species (ROS) and pro- and anti-inflammatory cytokines, events that disrupt vascular homeostasis, we hypothesized that CHIKV induces arterial dysfunction by directly impacting redox-related mechanisms in vascular cells. Wild-type (WT) and iNOS knockout (iNOS−/−) mice were administered either CHIKV (1.0 × 106 PFU/µL) or Mock vehicle via the intracaudal route. In vivo, CHIKV infection induced vascular dysfunction (assessed by a wire myograph), decreased systolic blood pressure (tail-cuff plethysmography), increased IL-6 and IFN-γ, but not TNF-α levels (determined by ELISA), and increased protein content by Western blot. Marked contractile hyporesponsiveness to phenylephrine was observed 48 h post-infection, which was restored by endothelium removal. L-NAME, 1400W, Tiron, and iNOS gene deletion prevented phenylephrine hyporesponsiveness. CHIKV infection increased vascular nitrite concentration (Griess reaction) and superoxide anion (O2•−) generation (lucigenin chemiluminescence), and decreased hydrogen peroxide (H2O2, by Amplex Red) levels 48 h post-infection, alongside increased TBARS levels. In vitro, CHIKV infected endothelial cells (EA.hy926) and upregulated ICAM-1 and iNOS protein expression (determined by Western blot). These data support the conclusion that CHIKV-induced alterations in vascular ROS/NF-kB/iNOS/NO signaling potentially contribute to cardiovascular events associated with Chikungunya infection. [ABSTRACT FROM AUTHOR]

17β-estradiol plays a crucial role in regulating cellular processes in both reproductive and non-reproductive tissues, including the thyroid gland. It modulates oxidative stress and contributes to sexual dimorphism in thyroid diseases, with ROS production, particularly H2O2, generated by NOX/DUOX enzymes. This study aimed to investigate the effects of 17β-estradiol (10 nM or 100 nM) on the expression of NOX/DUOX, thyroid-specific genes, and endoplasmic reticulum (ER) stress-related genes in male and female porcine thyroid follicular cells. Expression of the studied genes was evaluated by RT-PCR before and after treatment with 17β-estradiol alone or with the addition of NOX4 inhibitor (GKT-136901). Additionally, the level of ROS was measured by flow cytometry analysis. Our results show that 17β-estradiol significantly upregulates thyroid-specific genes, particularly TPO, and stimulates NOX/DUOX expression, affecting the redox state of thyroid cells. It also stimulates ER stress-related genes such as CHOP. In conclusion, estrogen excess may contribute to thyroid disease development via such possible mechanisms as the upregulation of key thyroid-specific genes, particularly TPO, and of genes involved in the cellular response to ER stress, especially CHOP, as well as by the stimulation of the NOX/DUOX system with consequent ROS overproduction. These mechanisms may play a certain role in the higher prevalence of thyroid diseases in women. [ABSTRACT FROM AUTHOR]

Catheter-associated urinary tract infections (CAUTIs) present significant health risks in medical settings, necessitating innovative solutions to prevent bacterial colonization on catheter surfaces. This study introduces a novel polymeric coating with dual antifouling and light-activated bactericidal properties to enhance the bactericidal efficacy of urinary catheters. The coatings were synthesized using a one-step process involving pyrogallol chemistry to deposit a copolymer composed of zwitterionic sulfobetaine for antifouling and sodium copper chlorophyllin, a photosensitizer that generates reactive oxygen species under light exposure to effectively kill bacteria. We evaluated the antifouling properties, cytocompatibility, and bactericidal performance of the coatings under various light conditions. The results showed significant reductions in bacterial adhesion, with light activation further endowing the catheter with bactericidal effects. Additionally, light could be delivered through an optical fiber within the catheter lumen to target and kill bacteria. The innovative coating using light-activated bactericidal action offers a promising approach to preventing CAUTIs, representing a potential breakthrough in developing safer and more effective urinary catheters. [ABSTRACT FROM AUTHOR]

Simple Summary: The International Agency for Research on Cancer (IARC) projects that by 2040, the global incidence of cancer would reach 27.5 million new cases. The current primary modalities of cancer treatment encompass surgery, radiation, and chemotherapy, which can harm normal tissues or fail to fully eliminate cancer. Nanomaterials make it easier to keep an eye on surgeries that remove tumors, deliver chemotherapy directly and selectively to cancer cells and neoplasms, and make radiation therapy more effective. It mitigates the risk and enhances the survival of cancer patients. This review aims to consolidate various metal peroxide nanomaterials utilized in cancer treatment with a special emphasis on metal peroxide nanoparticle surface modification for enhancing the efficacy of nanomaterials in tumor microenvironment. Researchers can acquire knowledge regarding metal peroxide nanoparticle types, their mechanisms of action, and their contributions to existing cancer medicines for enhanced cancer management. Background: The significant expansion of nanobiotechnology and nanomedicine has led to the development of innovative and effective techniques to combat various pathogens, demonstrating promising results with fewer adverse effects. Metal peroxide nanoparticles stand out among the crucial yet often overlooked types of nanomaterials, including metals. These nanoparticles are key in producing oxygen (O2) and hydrogen peroxide (H2O2) through simple chemical reactions, which are vital in treating various diseases. These compounds play a crucial role in boosting the effectiveness of different treatment methods and also possess unique properties due to the addition of metal ions. Methods: This review discusses and analyzes some of the most common metal peroxide nanoparticles, including copper peroxide (CuO2), calcium peroxide (CaO2), magnesium peroxide (MgO2), zinc peroxide (ZnO2), barium peroxide (BaO2), and titanium peroxide (TiOx) nanosystems. These nanosystems, characterized by their greater potential and treatment efficiency, are primarily needed in nanomedicine to combat various harmful pathogens. Researchers have extensively studied the effects of these peroxides in various treatments, such as catalytic nanotherapeutics, photodynamic therapy, radiation therapy, and some combination therapies. The tumor microenvironment (TME) is particularly unique, making the impact of nanomedicine less effective or even null. The presence of high levels of reactive oxygen species (ROS), hypoxia, low pH, and high glutathione levels makes them competitive against nanomedicine. Controlling the TME is a promising approach to combating cancer. Results: Metal peroxides with low biodegradability, toxicity, and side effects could reduce their effectiveness in treating the TME. It is important to consider the distribution of metal peroxides to effectively target cancer cells while avoiding harm to nearby normal cells. As a result, modifying the surface of metal peroxides is a key strategy to enhance their delivery to the TME, thereby improving their therapeutic benefits. Conclusions: This review discussed the various aspects of the TME and the importance of modifying the surface of metal peroxides to enhance their therapeutic advantages against cancer, as well as address safety concerns. Additionally, this review covered the current challenges in translating basic research findings into clinical applications of therapies based on metal peroxide nanoparticles. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia refers to an acute event of cerebral ischemia and hypoxia during the perinatal period, leading to various degrees of brain injury. The mechanisms involved in perinatal asphyxia include the production of reactive oxygen species (ROS), accumulation of intracellular calcium, lipid peroxidation, excitatory amino acid receptor overactivation, energy failure, and caspase-mediated cell death. Both primary and secondary neuronal damage are caused by the overproduction of ROS following a hypoxic/ischemic event. ROS can react with nearly any type of molecule, including lipids, proteins, polysaccharides, and DNA. Neonates who suffer from perinatal asphyxia are prone to oxidative stress, which is characterized by a disruption in the oxidant/antioxidant balance, favoring oxidants over the intracellular and extracellular antioxidant scavenging mechanisms. Current research has focused on developing treatment strategies that potentially improve the endogenous antioxidant neuroprotective mechanisms or minimize injury resulting from hypoxia/ischemia. In this narrative review, we aim to present evidence regarding the contribution of oxidant/antioxidant balance to the pathogenesis and progression of perinatal asphyxia. Also, we aim to explore the role of potential antioxidant therapies as promising treatment strategies for perinatal asphyxia, especially as an adjunct to therapeutic hypothermia in infants with perinatal asphyxia. The current literature on antioxidant treatments in newborns is limited; however, allopurinol, melatonin, and erythropoietin have shown some positive effects in clinical trials. Inhibitors of nitric oxide synthase, N-acetylcysteine, and docosahexaenoic acid have shown promising neuroprotective effects in preclinical studies. Finally, nanotherapeutics could potentially modulate oxidative stress in hypoxemic/ischemic brain injury by targeted medication delivery. Future research on neuroprotectants and their processes is warranted to develop innovative treatments for hypoxia/ischemia in clinical practice. [ABSTRACT FROM AUTHOR]

Low-temperature freezing stress constitutes the most significant meteorological disaster during the overwintering period in the Nanfeng Tangerine (NT) production area, severely impacting the normal growth and development of the plants. Currently, the accuracy of meteorological disaster warnings and forecasts for NT orchards remains suboptimal, primarily due to the absence of quantitative meteorological indicators for low-temperature freezing stress. Therefore, this study employed NT plants as experimental subjects and conducted controlled treatment experiments under varying intensities of low-temperature freezing stress (0 °C, −2 °C, −5 °C, −7 °C, and −9 °C) and durations (1 h, 4 h, and 7 h). Subsequently, physiological and biochemical parameters were measured, including photosynthetic parameters, chlorophyll fluorescence parameters, reactive oxygen species, osmoregulatory substances, and antioxidant enzyme activities in NT plants. The results demonstrated that low-temperature freezing stress adversely affected the photosynthetic system of NT plants, disrupted the dynamic equilibrium of the antioxidant system, and compromised cellular stability. The severity of freezing damage increased with decreasing temperature and prolonged exposure. Chlorophyll (a/b) ratio (Chl (a/b)), maximum quantum yield of photosystem II (Fv/Fm), soluble sugar, and malondialdehyde (MDA) were identified as key indicators for assessing physiological and biochemical changes in NT plants. Utilizing these four parameters, a comprehensive score (CS) model of freezing damage was developed to quantitatively evaluate the growth status of NT plants across varying low-temperature freezing damage gradients and durations. Subsequently, the freezing damage grade index for NT plants during the overwintering period was established. Specifically, Level 1 for CS ≤ −0.50, Level 2 for −0.5 < CS ≤ 0, Level 3 for 0 < CS ≤ 0.5, and Level 4 for 0.5 < CS. The research results provide valuable data for agricultural meteorological departments to carry out disaster monitoring, early warning, and prevention and control. [ABSTRACT FROM AUTHOR]

Salt stress is a major abiotic factor that negatively impacts the growth, performance, and secondary metabolite production in pepper (Capsicum annuum L.) plants. Brassinosteroids (BRs) play a crucial role in enhancing plant tolerance to abiotic stress, yet their potential in mitigating salt stress in pepper plants, particularly by promoting sugar and glycine betaine accumulation, remains underexplored. In this study, we investigated the effects of the foliar application of 2,4-epibrassinolide (EBR) on salt-stressed pepper seedlings. Our findings revealed that EBR treatment significantly increased the levels of proline, sugar, and glycine betaine under salt stress compared to untreated controls. Moreover, EBR enhanced the antioxidant defense mechanisms in pepper seedlings by increasing sugar and glycine betaine levels, which contributed to the reduction of reactive oxygen species (ROS) and malondialdehyde (MDA) accumulation. [ABSTRACT FROM AUTHOR]

Acyl-CoA-binding protein (ACBP) genes have been implicated in lead enrichment and translocation in plants; however, the mechanisms by which these genes contribute to the response to heavy metal stress in various taxa have not been determined. In this study, the molecular mechanisms underlying the response of Robinia pseudoacacia, an economically important deciduous tree, to Pb stress were examined using transcriptomic and metabolomic analyses. RpACBP3 overexpression increased Pb enrichment, translocation, and tolerance. After Pb stress for 3 days, 1125 differentially expressed genes (DEGs) and 485 differentially accumulated metabolites (DAMs) were identified between wild-type and RpACBP3-overexpressing R. pseudoacacia strains; after Pb stress for 45 days, 1746 DEGs and 341 DAMs were identified. Joint omics analyses showed that the DEGs and DAMs were co-enriched in α-linoleic acid metabolism and flavonoid biosynthesis pathways. In particular, DEGs and DAMs involved in α-linoleic acid metabolism and flavonoid biosynthesis were up- and down-regulated, respectively. Moreover, RpACBP3 overexpression enhanced the ability to scavenge reactive oxygen species and repair cell membranes under stress by regulating LOX gene expression and increasing the phosphatidylcholine content, thereby improving the tolerance to Pb stress. These findings lay a theoretical foundation for the future application of RpACBP3 genes in plant germplasm resource creation and phytoremediation of Pb contaminated soil in which R. pseudoacacia grow. [ABSTRACT FROM AUTHOR]

Soybean, an important cash crop, is often affected by soil salinity, which is one of the important types of abiotic stress that affects its growth. Poly (acrylic) acid coated Mn3O4 (PMO) has been reported to play a vital role in defending against a variety of abiotic stresses in plants. To date, the effects of PMOs on soybean have not been reported; this study explored the mechanism of PMO-enhanced soybean germination under salt stress. In this experiment, 100 mg/L PMO was used as an immersion agent with a salt treatment of 150 mM NaCl. The results showed that when compared with the PMO treatment, salt stress significantly decreased the germination rate, fresh weight, carbohydrate content, and antioxidant enzyme activity of soybean and significantly increased the contents of reactive oxygen species, malondialdehyde, and osmoregulatory substances. However, PMO treatment enhanced the antioxidant defense system and significantly reduced the malondialdehyde content of soybean. Moreover, the activities of H+-ATPase and Ca2+-ATPase were significantly higher in treated soybean than in the control, and the content of ATP was also higher in treated soybean than in the control. Generally, PMO regulates the homeostasis of reactive oxygen species and reduces ATP consumption, thereby improving the ability of soybeans to germinate under salt stress. This study provides new insights into how nanomaterials improve plant salt tolerance. [ABSTRACT FROM AUTHOR]

Drought is one of the most important abiotic factors limiting plant productivity. Although the aromatic plants of the Lamiaceae family often grow in arid regions, drought tolerance varies greatly among the different species of this family. The effect of induced drought stress can be reduced by the application of selenium. The current study aims to compare the growth and biochemical responses of three species of the Lamiaceae family (hyssop, salvia, and oregano) to drought stress and the possibility of reducing the effect of stress in these plants by foliar treatment with selenium. Drought stress reduced the fresh and dry biomass of hyssop (by 35% and 15%), salvia (by 45% and 41%), and oregano (by 51% and 32%). Se treatment did not affect the growth of plants under drought stress, but it improved relative water content in hyssop and salvia under moderate drought conditions. A reduction in the content of chlorophyll a and chlorophyll b (in hyssop and salvia). In addition, an increase in the content of hydrogen peroxide (in oregano and salvia), malondialdehyde, and proline in plants cultivated under drought conditions was observed. Se treatment led to reduced levels of hydrogen peroxide and malondialdehyde, along with an increase in chlorophyll a content (in hyssop and oregano) and proline content. The response of the antioxidant system depended on the plant species. Hyssop exhibited a significant increase in glutathione peroxidase, superoxide dismutase, and peroxidase activities. Oregano showed enhanced catalase activity. Salvia experienced a sharp increase in ascorbic acid content. Se treatment stimulated the accumulation of phenolic compounds and increased glutathione peroxidase activity in all studied species. [ABSTRACT FROM AUTHOR]

Chilling stress, a common abiotic factor, adversely affects the growth and biomass of rice seedlings during the early stages, ultimately reducing the yield. Effective strategies to mitigate these negative impacts are essential for improving rice productivity. The application of nanotechnology in agriculture, particularly nanoparticles (NPs), has shown a promising effect in alleviating chilling stress in plants. This study evaluates the effects of various nanoparticles, ZnO (0, 50, 100, and 200 mg/L), Fe2O3 (0, 50, 75, and 100 mg/L), TiO2 (0, 50, 75, and 100 mg/L), and CeO2 (0, 50, 75, and 100 mg/L) on the chilling resistance with one control (a water spray) under a normal temperature. Four rice cultivars: LLY-7108 and XZX-6 (Low-temperature-tolerant), and LLY-32 and ZJZ-17 (Low-temperature-susceptible) were tested in this experiment. Rice seedlings were subjected to low temperature conditions (12 h light 14 °C/12 h dark, at 10 °C) for five days, followed by seven days of recovery. The results of this study demonstrate that NPs significantly enhanced seedling height fresh/dry weight and root length compared to untreated controls under chilling stress. NP treatment also reduced the reactive oxygen species (ROS), malondialdehyde (MDA), and proline content, while enhancing superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities, thereby mitigating oxidative damage. The four rice varieties exhibited clear signs of rapid growth recovery and positive physiological changes due to NPs' application. Among the tested cultivars, LLY-7108 showed the most substantial recovery and physiological responses, while ZJZ-17 exhibited the least. The findings of this study indicate that the foliar application of ZnO (100 mg/L), Fe2O3 (50 mg/L), TiO2 (50 mg/L), and CeO2 (75 mg/L) NPs effectively mitigates chilling stress in rice seedlings, likely by enhancing the antioxidant enzymatic activity while reducing the oxidative damage. This study highlights the potential of NPs as effective agents in reducing the adverse effects of chilling stress on rice. [ABSTRACT FROM AUTHOR]

Rosa Roxburghii (RR), a traditional Chinese medicinal fruit, is rich in bioactive substances that make it a potential natural antioxidant resource. This research aimed to study the antioxidant properties of RR by in vitro experiments and through intracellular assessment in H2O2-induced HepG2 cells. A non-targeted metabolic analysis was conducted to indicate changes in intracellular and extracellular metabolites. Differential metabolites and metabolic pathways were explored using PCA, PLS-DA, and KEGG pathway analysis. The results showed that RR rich in bioactive substances exhibited a significant antioxidative property in vitro and intracellularly. This property may be achieved by scavenging free radicals, increasing the activity of catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and the levels of bicinchoninic acid (BCA) while reducing the reactive oxygen species (ROS) generation. This study identified 13 differential metabolites intracellularly and 7 extracellularly, among which the key differential metabolites included D-glucopyranose, D-mannose, fructose, citric acid, malic acid, cholesterol, and cholestenone. These key metabolites primarily regulated glucose-related metabolism, the citrate cycle, and the primary bile acid biosynthesis pathway in H2O2-induced HepG2 cells. These findings provide potential application evidence of RR in the development of natural resources for functional foods. [ABSTRACT FROM AUTHOR]

Bambara groundnut (BG)-based films containing seed coat extract at different concentrations were prepared and characterized. BG seed coat extract (BGSCE) had a total phenolic content of 708.38 mg GAE/g dry extract. BGSCE majorly consisted of quercetin 3-galactoside, rutin, and azaleatin 3-arabinoside. BGSCE exhibited ABTS and DPPH radical scavenging activities (ABTS-RSAs and DPPH-RSAs), a ferric reducing antioxidant power (FRAP), and an oxygen radical absorbance capacity (ORAC) of 66.44, 4.98, 4.42, and 0.91 mmol Trolox equivalent/g dry extract, respectively. When BGSCE at various concentrations (0–8%, w/w, protein content) was incorporated into the BG protein isolate (BG-PI)-based films, film containing 4% BGSCE exhibited higher thickness, tensile strength, elongation at break, water vapor and UV-light barrier properties, and a*-value (redness) than the control film (p < 0.05). Films containing BGSCE had greater ABTS-RSA, FRAP, and ORAC than the control film (p < 0.05). An FTIR analysis elucidated that the proteins interacted with phenolic compounds in BGSCE. Nonetheless, less thermal stability was attained in films added with BGSCE. Hence, the addition of BGSCE possessing antioxidant activity exhibited an important role in properties and characteristics of BG-PI-based film. The developed active film could be applied as packaging material possessing antioxidant property for food applications. [ABSTRACT FROM AUTHOR]

This study aimed to explore the mechanism by which phenethyl isothiocyanate (PEITC) inhibited the adhesion and biofilm formation of Staphylococcus aureus (S. aureus). PEITC exhibited antimicrobial efficacy against S. aureus, demonstrating a minimum inhibition concentration (MIC) of 1 mmol/L. PEITC exerted its antibacterial effect by disrupting cell membrane integrity, and it decreased total adenosine triphosphate (ATP) production after 1 and 4 h treatment. PEITC at 0.5 mmol/L increased the level of intracellular reactive oxygen species (ROS) by 26.39% compared to control. The mature biofilm of S. aureus was destroyed by 86.4% after treatment with PEITC for 24 h. Adhesion tests revealed that PEITC at 0.5 mmol/L reduced 44.51% of the S. aureus that adhered to NCM460 cells. Furthermore, at the genetic level, PEITC significantly downregulated the related genes by 31.26% to 97.04%, including agrB, agrD, isdA, ebh, luxS, fnbA, and icaR. Moreover, PEITC markedly inhibited S. aureus proliferation in beef preserved at temperatures of 25 and 4 °C, respectively. In summary, the present study suggests that PEITC effectively inhibits the adhesion and biofilm formation of S. aureus by affecting the relevant genes of S. aureus and holds promise for microbial management in meat products. [ABSTRACT FROM AUTHOR]

Pericarp browning and fruit decay severely reduce the postharvest quality of litchi. Improving the antioxidant capacity of the fruit is an effective way to solve these problems. In our study, the appropriate zinc oxide nanoparticles (ZnO NPs) treatment and its mechanism of action on the storability of litchi was investigated. Litchi fruit was soaked in a 100 mg·L−1 ZnO NPs suspension, water, and 500 mg·L−1 prochloraz for 2 min, respectively. The results showed that the ZnO NPs treatment delayed pericarp browning and decay in litchi fruit and was more effective than prochloraz treatment. The ZnO NPs-treated fruit showed significantly increased contents of total anthocyanin, total phenols, and activities of DPPH scavenging, superoxide dismutase, and glutathione peroxidase, as well as the lowest activities of polyphenol oxidase and laccase. ZnO NPs generated hydrogen peroxide and superoxide anion radicals, which were beneficial in slowing down the decay and inducing antioxidant capacity. However, these reactive oxygen species also consumed catalase, peroxidase, glutathione, and glutathione peroxidase. This means that litchi should be treated with an appropriate concentration of ZnO NPs. We concluded that treatment with a 100 mg·L−1 ZnO NPs suspension could induce antioxidant capacity, which is a promising and effective method to maintain the postharvest quality of litchi. [ABSTRACT FROM AUTHOR]

Theobromine (TBR) is a methylxanthine known for its bronchodilatory and stimulatory effects. This research evaluated the vitality, capacitation patterns, oxidative characteristics, microbial profile and expression of capacitation-associated proteins (CatSper1/2, sodium bicarbonate cotransporter [NBC], protein kinases A [PKA] and C [PKC] and adenylate cyclase 10 [ADCY10]) in cryopreserved bovine spermatozoa (n = 30) in the absence (cryopreserved control [CtrlC]) or presence of different TBR concentrations (12.5, 25, and 50 µM) in egg yolk extender. Fresh ejaculate served as a negative control (CtrlN). Significant post-thaw maintenance of the sperm motility, membrane and DNA integrity and mitochondrial activity (p < 0.001) were recorded following the administration of 25 μM and 50 μM TBR, then compared to CtrlC. All groups supplemented with TBR exhibited a significantly lower percentage of prematurely capacitated spermatozoa (p < 0.001) than CtrlC. Significantly decreased levels of global reactive oxygen species (ROS), hydrogen peroxide and hydroxyl radicals were observed in the presence of 25 μM and 50 μM TBR (p < 0.01). Western blot analysis revealed that supplementation with 50 μM TBR significantly prevented the loss of NBC and ADCY10 (p < 0.01), while all TBR doses stabilized the levels of PKC (p < 0.05 at 50 μM TBR; p < 0.001 at 12.5 μM and 25 μM TBR). In summary, we suggest that TBR is effective in protecting the spermatozoa during the cryopreservation process through its potential to stimulate energy synthesis while preventing ROS overproduction and the loss of proteins involved in the sperm activation process. [ABSTRACT FROM AUTHOR]