Search Results (498)

Multiple sclerosis (MS) is a complex disease marked by chronic neuroinflammation and reactive oxygen species (ROS) toxicity in the central nervous system (CNS). Based on this ROS-driven mechanism, we tested whether PrC-210—a new aminothiol ROS scavenger—could lessen MS symptoms in mice with experimental autoimmune encephalomyelitis (EAE)-induced MS. Our goals were to assess the role of ROS in MS and evaluate the potential benefits of PrC-210 for managing MS. Mice with EAE received varying doses of PrC-210 under preventive and therapeutic protocols. Disease progression was measured using clinical scores and spinal cord histology. Safety was assessed by comparing the gastrointestinal and hematological toxicity between PrC-210 and dimethyl fumarate (DMF, Tecfidera’s active agent). PrC-210 reduced MS severity by up to 62% in paralysis scores versus those in the controls (p = 0.0001), whether used preventively or at the onset of paralysis. The group with the greatest decrease also showed the best spinal cord preservation and least demyelination. DMF caused toxicity at a dose that was ineffective, while PrC-210 showed no toxicity at effective levels. These findings suggest that the systemic administration of PrC-210 may offer a safe, effective MS treatment when started at symptom onset. Full article

Tris(2-chloroethyl) phosphate (TCEP), as an organophosphate contaminant, poses a significant threat to the growth and development of plants, especially roots. This study aimed to clarify the mechanisms of TCEP’s toxicity and damage to root systems, as well as the mechanisms of its damage to the respiration and energy metabolism of alfalfa root cells. The results showed that TCEP obviously affected the root length, root surface area, root volume, and root diameter of alfalfa. With increasing stress intensity, the total mitochondrial respiration rate and Cytochrome C Oxidase (COX) pathway respiration rate progressively declined, while the Alternative Oxidase (AOX) pathway respiration rate and its proportion of total respiration gradually rose. In addition, adenosine triphosphate (ATP) content and root vigor were significantly reduced. Moreover, with an increase in TCEP concentration, root superoxide anion radical content in alfalfa root cells was significantly elevated, while superoxide dismutase (SOD) and catalase (CAT) activities were significantly lowered, and ascorbate peroxidase (APX) and peroxidase (POD) activities were significantly enhanced. The present study indicated that respiration was disrupted, causing a lack of ATP in root cells under TCEP. Both the overproduction of reactive oxygen species (ROS) from the mitochondrial respiratory electron transport chain (mECT) and the deficiency of ROS-scavenging enzymes caused ROS accumulation, which led to the destruction of the cell membrane structure and exacerbated the disruption of the respiratory metabolism. The disruption of the conversion and reuse of energy by TCEP affected root growth and development. Full article

Peanut (Arachis hypogaea L.) is an important oil and cash crop, but its growth and productivity are severely constrained by low-temperature stress. Growth-regulating factors (GRFs) are plant-specific transcription factors involved in development and stress responses, yet their roles in peanut remain poorly understood. In this study, we identified AhGRF3b as a direct target of ahy-miR396 using degradome sequencing, which demonstrated precise miRNA-mediated cleavage sites within the AhGRF3b transcript. Expression profiling confirmed that ahy-miR396 suppresses AhGRF3b via post-transcriptional cleavage rather than translational repression. Functional analyses showed that overexpression of AhGRF3b in Arabidopsis thaliana promoted leaf expansion by enhancing cell proliferation. Specifically, leaf length, width, and petiole length increased by 104%, 22%, and 28%, respectively (p < 0.05). Under cold stress (0 °C for 7 days), transgenic lines (OE-2 and OE-6) exhibited significantly better growth than Col-0, with fresh weight increased by 158% and 146%, respectively (p < 0.05). Effect size analysis further confirmed these differences (Cohen’s d = 11.6 for OE-2 vs. Col-0; d = 6.3 for OE-6 vs. Col-0). Protein–protein interaction assays, performed using the yeast two-hybrid (Y2H) system and 3D protein–protein docking models, further supported that AhGRF3b interacts with Catalase 1 (AhCAT1), vacuolar cation/proton exchanger 3 (AhCAX3), probable polyamine oxidase 4 (AhPAO4), and ACT domain-containing protein 11 (AhACR11), which are involved in reactive oxygen species (ROS) scavenging and ion homeostasis. These interactions were associated with enhanced CAT and PAO enzymatic activities, reduced ROS accumulation, and upregulation of stress-related genes under cold stress. These findings suggest that the ahy-miR396/AhGRF3b module plays a potential regulatory role in leaf morphogenesis and cold tolerance, providing valuable genetic resources for breeding cold-tolerant peanut varieties. Full article

The immune system is crucial in protecting against disease, but it can also contribute to chronic illnesses when it malfunctions, with different conditions involving either inflammation or immune suppression. Current treatments often fall short due to limited effectiveness and side effects. Nanomedicine, particularly cerium oxide nanoparticles (nanoceria), offers promising potential due to its unique therapeutic properties and role in modulating macrophages. Nanoceria (<5 nm) possess the catalytic ability to mimic natural enzymes such as superoxide dismutase, peroxidase, and catalase, enabling effective scavenging of reactive oxygen species (ROS), which play a central role in the pathogenesis of chronic inflammation and cancer. This review comprehensively summarizes the current advances in the application of nanoceria for inflammatory and anti-inflammatory therapy, including their modulatory effects on immune cell activation, cytokine production, and resolution of inflammatory responses. We discuss the mechanisms underlying their immunomodulatory actions in various disease contexts, such as rheumatoid arthritis, women’s health conditions (e.g., endometriosis), wound healing, and cancer. Additionally, the review highlights biocompatibility, therapeutic efficacy, adaptability in imaging (theranostics), and challenges in translating nanoceria-based therapies into clinical practice. The multifunctionality of nanoceria positions them as innovative candidates for next-generation immunotherapy aimed at efficiently controlling inflammation and promoting tissue repair. Full article

Background/Objectives: Ulcerative colitis (UC) involves chronic colon inflammation and oxidative stress. Treating UC is challenging due to systemic drug side effects and poor targeted delivery. Nanocarriers responsive to the UC microenvironment, particularly elevated reactive oxygen species (ROS), could overcome these limitations. This study developed an oral delivery system for ROS-triggered drug release and active targeting. Using ferulic acid (FER), a system was designed to enhance site-specific accumulation and therapeutic efficacy against colitis. Methods: A ROS-sensitive covalent organic framework (COF) was synthesized from γ-cyclodextrin and functionalized with folic acid (FA) to create a carrier (COF-FA) designed for potential active targeting. This carrier was loaded with FER to form FER@COF-FA. The system was characterized (SEM, FTIR, TGA), and its ROS scavenging and sustained drug release profiles were confirmed in vitro. Biocompatibility was evaluated in cell lines, and therapeutic efficacy was tested in a DSS-induced murine colitis model. Results: The synthesized FER@COF-FA demonstrated high drug loading, potent ROS-scavenging capability, and a sustained drug release profile. It showed excellent biocompatibility and, in the murine model, significantly outperformed free FER. Treatment alleviated disease severity, prevented colon shortening, restored healthy tissue histology, and rebalanced pro- and anti-inflammatory cytokines. Conclusions: The FER@COF-FA system represents a highly promising therapeutic strategy for UC. Its superior efficacy is attributed to a synergistic multi-mechanism approach, combining sustained release, ROS-responsive drug delivery, intrinsic antioxidant activity, and potential folate receptor-mediated targeting, which collectively enhance site-specific accumulation and therapeutic outcomes in the inflammatory colon microenvironment. Full article

Lycium barbarum L. (goji berry) undergoes rapid quality deterioration after harvest owing to its high water activity and abundant reactive oxygen species (ROS). Carbon-dot-mediated photodynamic treatment (CD-PDT) has recently been shown to extend shelf life by modulating ROS-scavenging and defense enzymes, yet the global metabolic reprogramming that supports this protection remains unresolved. Here, we applied ultra-high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS)-based untargeted metabolomics to decode the metabolic footprint of CD-PDT in freshly harvested goji berries. Our results revealed a total of 17,603 differentially expressed metabolites between the treatment and control groups under both positive- and negative-ion modes. Principal component analysis indicated that CD-mediated PDT significantly altered the metabolic profile of fresh goji berries. The treatment activated the phenylpropanoid biosynthesis pathway, promoting the accumulation of compounds such as kaempferol-3-sophoroside, kaempferol-3-O-β-D-glucoside, and galactoside, thereby enhancing the antioxidant capacity of the fruit. Furthermore, CD-mediated PDT induced the tricarboxylic acid cycle, providing sufficient energy to support the phenylpropanoid biosynthesis pathway. In conclusion, these findings provide the systems-level evidence that CD-PDT orchestrates a coordinated activation of primary and secondary metabolism in postharvest goji berries, establishing a mechanistic framework for preservation of horticultural products. Full article

In the light reactions of photosynthesis, reactive oxygen species (ROS), such as superoxide anion radical (O₂^•−), hydrogen peroxide (H₂O₂), singlet oxygen (¹O₂*), and hydroxyl radical (OH^•), are continuously generated at basal levels and are kept in homeostasis by the antioxidative enzymatic and non-enzymatic systems. Nevertheless, under abiotic or biotic stress conditions, this balance between the creation and elimination of ROS is disrupted, and the increased ROS production leads to oxidative stress, which is involved in the growth retardation of plants. However, ROS are also beneficial, since they trigger the plant’s defense mechanisms for handling oxidative stress and are fundamental signaling molecules for the regulation of a range of physiological functions under optimum growth conditions or environmental stress circumstances, activating a plethora of acclimation responses. Gaining insight into the relationship between ROS generation, ROS scavenging, and the protective role of ROS will contribute to improving agricultural sustainability in the face of global climate change. Full article

Heat stress (HS), a pervasive environmental stressor, significantly disrupts systemic physiological homeostasis, posing substantial threats to human and animal health. Sheng Mai San (SMS), a classic Traditional Chinese Medicine (TCM) formula, exerts its therapeutic effects by replenishing qi (the vital energy governing physiological functions) and nourishing yin (the material basis responsible for moistening and cooling actions). This formula demonstrates significant efficacy in astringing sweating and preventing collapse. However, its precise molecular mechanisms against HS-induced myocardial injury remain incompletely elucidated. This study initially employed physicochemical analytical methods to determine the contents of total polysaccharides, saponins, and flavonoids in SMS and evaluated its antioxidant activity. Subsequently, both in vitro and in vivo rat models of HS were established to systematically assess the alterations in reactive oxygen species (ROS), antioxidant enzymes (GSH, SOD, CAT), and heat shock proteins (HSP70, HSP90) following SMS intervention, thereby investigating HS-induced myocardial injury and the protective effects of SMS. Furthermore, Western blot, immunofluorescence, and qRT-PCR techniques were utilized to quantitatively analyze key molecules in the Keap1-Nrf2-HO-1 and Stub1-HSF1 signaling pathways. The results demonstrated that total polysaccharides were the most concentrated in SMS, followed by total saponins. This formula exhibited potent free radical scavenging capacity against DPPH, ABTS, and OH⁻, along with significant reducing activity. HS-induced myocardial injury reached its peak severity at 6-12 h post-stress exposure. SMS intervention effectively suppressed excessive ROS generation, enhanced the activities of antioxidant enzymes (GSH, SOD, and CAT), and downregulated HSP70 and HSP90 mRNA expression levels, thereby significantly mitigating cardiomyocyte damage. Mechanistic investigations revealed that SMS conferred cardioprotection through dual modulation of the Keap1-Nrf2-HO-1 and Stub1-HSF1 signaling pathways. This study not only provides a novel TCM-based therapeutic strategy for preventing and treating HS-related cardiovascular disorders but also establishes a crucial theoretical foundation for further exploration of SMS’s pharmacological mechanisms and clinical applications. Full article

Drought represents a paramount constraint on global agricultural productivity, imposing severe limitations on crop yield and quality across diverse agroecosystems. Nitrogen (N), functioning as an indispensable macronutrient fundamental to plant architecture, metabolism, and stress acclimatization, exerts a pivotal influence in modulating plant resilience to water deficit. Substantial evidence accumulated in recent years underscores that optimal N nutrition significantly enhances plant adaptive capacity under drought by improving intrinsic water use efficiency (WUEi), optimizing photosynthetic performance, augmenting antioxidant defense systems, promoting advantageous root architectural modifications, and stabilizing biological N fixation (BNF) symbioses. This comprehensive review synthesizes current knowledge on the intricate physiological and molecular mechanisms underpinning N-mediated drought mitigation. We meticulously examine regulatory roles of N in water relations and hydraulic conductivity, photosynthetic apparatus protection and carbon assimilation efficiency, N metabolic flux and assimilation homeostasis, reactive oxygen species (ROS) scavenging and osmotic adjustment, root system development and resource foraging strategies, BNF system robustness under water stress, and the complex signaling networks integrating N and drought responses. Furthermore, we critically evaluate existing research consensus, identify persisting controversies and knowledge gaps, and delineate future research trajectories and translational challenges. The overarching objective is to furnish a robust theoretical foundation for devising precision N management strategies and advancing the breeding of drought-resilient, nutrient-efficient crop cultivars suited to arid and semi-arid regions facing escalating climate variability. Full article

Immunoregulation is an emerging treatment strategy to promote wound healing by modulating the local immune system at the wound site. In this study, an extracellular matrix biomimetic and polysaccharide-based hydrogel was engineered to regulate the wound immune environment through Michael-type addition between maleimidyl pullulan and chitosan modified with hydroxyproline. The proposed hydrogel exhibited favorable injectable and self-healing properties, which facilitated the full coverage of irregularly shaped wounds. A natural polyphenol, epigallocatechin-3-gallate (EGCG), was incorporated into hydrogels, which thereby exhibited excellent biocompatibility, good reactive oxygen species (ROS) scavenging ability, anti-inflammatory activity, and antibacterial properties against S. aureus and E. coli. Furthermore, evaluations of a full-thickness skin defect mice model showed that the hydrogel with EGCG effectively alleviated the inflammatory response by reducing pro-inflammatory cellular infiltration and down-regulating the inflammatory cytokine TNF-α, while up-regulating anti-inflammatory cytokine IL-10. Notably, a faster wound healing rate was also achieved by the better promotion effect of the hydrogel on increasing the formation of re-epithelialization, granulation tissue generation, collagen deposition, and angiogenesis. Therefore, our immunoregulatory strategy showed great potential in the design of biomaterials for wound management. Full article

Climate change is intensifying the co-occurrence of drought and heat stresses, which substantially constrain global crop yields and threaten food security. Developing climate–resilient crop varieties requires a comprehensive understanding of the physiological and molecular mechanisms underlying combined drought–heat stress tolerance. This review systematically summarizes recent advances in integrating multi-scale remote-sensing phenomics with multi-omics approaches—genomics, transcriptomics, proteomics, and metabolomics—to elucidate stress response pathways and identify adaptive traits. High-throughput phenotyping platforms, including satellites, UAVs, and ground-based sensors, enable non-invasive assessment of key stress indicators such as canopy temperature, vegetation indices, and chlorophyll fluorescence. Concurrently, omics studies have revealed central regulatory networks, including the ABA–SnRK2 signaling cascade, HSF–HSP chaperone systems, and ROS-scavenging pathways. Emerging frameworks integrating genotype × environment × phenotype (G × E × P) interactions, powered by machine learning and deep learning algorithms, are facilitating the discovery of functional genes and predictive phenotypes. This “pixels-to-proteins” paradigm bridges field-scale phenotypes with molecular responses, offering actionable insights for breeding, precision management, and the development of digital twin systems for climate-smart agriculture. We highlight current challenges, including data standardization and cross-platform integration, and propose future research directions to accelerate the deployment of resilient crop varieties. Full article

Neutrophils are the first line of defense of the human immune system against pathogens. Photobiomodulation, mediated by mitochondrial photoacceptors such as cytochrome c oxidase, has emerged as a method to modulate neutrophil function through targeted light exposure. Despite the extensive characterization of neutrophil extracellular traps (NETs) formation (NETosis), the wavelength-specific modulation of neutrophil photoactivation and the involvement of redox pathways remain poorly defined. In this study, the effects of monochromatic (365 nm, 415 nm, 437 nm, and 625 nm) and dichromatic LED-light irradiation on NETs formation were systematically examined. The highest netotic responses were elicited by UV-A (365 nm) and violet-blue light (415 nm), whereas 437 nm showed the lowest induction and 625 nm stimulated a moderate netotic response. The pharmacological inhibition of NETosis induced by 365 nm and 415 nm irradiation with specific NADPH oxidase inhibitor, apocynin, and mitochondrial reactive oxygen species (mtROS) scavenger, MitoTEMPO, attenuated NETs formation by engaging both enzymatic and mitochondrial oxidative sources. Notably, mtROS played a dominant role under 415 nm stimulation in contrast to 365 nm-induced NETosis as demonstrated by higher sensitivity to MitoTEMPO. Importantly, combined simultaneous irradiation with 415 nm and 625 nm LEDs resulted in a significant suppression of NETs formation by more than 50%, highlighting a potent inhibitory synergy observed for the first time and suggesting a new approach of wavelength pairing to modulate neutrophil activation. These results were further supported by measurements of ROS production using a luminol-amplified chemiluminescence assay. Collectively, these findings delineate a wavelength- and ROS-dependent framework for light-induced neutrophil activation, with mitochondrial pathways exerting central control particularly under short-wavelength irradiation. Full article

Drought is one of the major abiotic stresses threatening maize production globally. Under drought stress, maize plants produce excessive reactive oxygen species (ROS), leading to oxidative damage. The apoplast, as the site of substance and signal exchange between plant cells and the external environment, is an important location for the production of ROS under drought stress. Elucidating the ROS scavenging mechanisms in the apoplast is crucial for understanding plant stress responses. However, there is still a lack of research on the ROS scavenging enzymes in maize apoplast and their mediated signaling pathways. We verified that maize peroxidase Prx25 (ZmPrx25) is localized in the apoplast, it scan scavenge hydrogen peroxide (H₂O₂), and we systematically investigated the responses of the apoplastic ZmPrx25-ROS system to osmotic stress. ROS accumulate in the apoplast of maize mesocotyl in response to osmotic stress and transmit the external osmotic stress signals from the apoplast to the inner cellular compartments. The expression of ZmPrx25 is highly upregulated in the meristematic regions of maize seedlings under osmotic and oxidative stress. Overexpression of ZmPrx25 in Arabidopsis promoted seed germination and plant growth, significantly enhancing tolerance to osmotic and oxidative stress. This study provides a new perspective on the role of Prx25 in scavenging ROS under drought stress. Full article

Soil salinity severely impairs crop productivity by inducing osmotic stress, ionic toxicity, and oxidative damage. This study investigated the mechanisms by which foliar-applied wood vinegar (WV), a biomass pyrolysis byproduct rich in organic acids and minerals, alleviates salt stress (100 mM NaCl) in hydroponically grown wheat (Triticum aestivum L.). Three WV dilutions (100×, 300×, 500×) were tested to evaluate their effects on growth, antioxidant systems, chlorophyll metabolism, and ion homeostasis. The results demonstrated that 300×-diluted WV (WV3) most effectively mitigated salt stress, increasing shoot biomass by 81% and root length by 75% compared to salt-stressed controls. WV3 restored antioxidant enzyme activities to non-stressed levels, reduced lipid peroxidation, and normalized chlorophyll overaccumulation induced by salinity. Elemental profiling revealed that WV3 enhanced shoot K⁺ and Ca²⁺ uptake while reducing Na⁺ accumulation, thereby improving ion homeostasis. Additionally, WV3 promoted Fe translocation to shoots, supporting chlorophyll synthesis. However, 100× WV (WV1) exhibited phytotoxicity due to excessive organic acids, while 500× (WV5) showed limited efficacy. These findings highlight a 300-fold diluted solution of WV as an optimal dilution for enhancing wheat salt tolerance through coordinated ROS scavenging, photosynthetic protection, and ion regulation. This study provides a scientific basis for integrating WV into sustainable strategies to combat salinity in wheat cultivation. Full article

Amiodarone (AMD) is an effective antiarrhythmic drug whose long-term use is limited by multi-organ toxicities linked to oxidative stress. This review synthesizes current evidence on how AMD induces reactive oxygen species (ROS) generation in vitro and in vivo, and the mechanistic pathways involved. AMD promotes ROS production through both direct and indirect mechanisms. Directly, AMD accumulates in mitochondria and impairs the electron transport chain, leading to electron leakage and superoxide formation. It also undergoes redox cycling, forming radical intermediates that trigger lipid peroxidation and deplete cellular antioxidants. AMD and its metabolites inhibit antioxidant enzymes (SOD, CAT, GPx) expression and/or activities and reduce glutathione level, compounding oxidative injury. Indirectly, AMD activates signaling pathways that exacerbate ROS generation. This compound can induce pro-inflammatory mediators such as TNF-α and modulate nuclear receptors such as AhR, PXR, CAR, and PPARs, altering the expression of metabolic enzymes and endogenous antioxidants. These processes are time- and dose-dependent: short exposures at low concentrations may transiently scavenge radicals, whereas chronic or higher-dose exposures consistently lead to net ROS accumulation. The oxidative effects of AMD vary by tissue and experimental models. In chronic models, organs such as the lung and liver show pronounced ROS-mediated injury, whereas acute or cell-based systems typically exhibit subtler changes. AMD-induced toxicity arises from multifactorial oxidative stress involving mitochondrial dysfunction, increased radical formation, depletion of antioxidant defenses, and activation of pro-oxidant signaling pathways. Recognizing these pathways suggests that antioxidant and mitochondria-targeted co-therapies could ameliorate the side effects of AMD. Full article