Reactive Oxygen Species Scavenger Research Articles

IP3R1 is required for meiotic progression and embryonic development by regulating mitochondrial calcium and oxidative damage

Calcium ions (Ca2+) regulate cell proliferation and differentiation and participate in various physiological activities of cells. The calcium transfer protein inositol 1,4,5-triphosphate receptor (IP3R), located between the endoplasmic reticulum (ER) and mitochondria, plays an important role in regulating Ca2+ levels. However, the mechanism by which IP3R1 affects porcine meiotic progression and embryonic development remains unclear. We established a model in porcine oocytes using siRNA-mediated knockdown of IP3R1 to investigate the effects of IP3R1 on porcine oocyte meiotic progression and embryonic development. The results indicated that a decrease in IP3R1 expression significantly enhanced the interaction between the ER and mitochondria. Additionally, the interaction between the ER and the mitochondrial Ca2+ ([Ca2+]m) transport network protein IP3R1-GRP75-VDAC1 was disrupted. The results of the Duolink II in situ proximity ligation assay (PLA) revealed a weakened pairwise interaction between IP3R1-GRP75 and VDAC1 and a significantly increased interaction between GRP75 and VDAC1 after IP3R1 interference, resulting in the accumulation of large amounts of [Ca2+]m. These changes led to mitochondrial oxidative stress, increased the levels of reactive oxygen species (ROS) and reduced ATP production, which hindered the maturation and late development of porcine oocytes and induced apoptosis. Nevertheless, after treat with [Ca2+]m chelating agent ruthenium red (RR) or ROS scavenger N-acetylcysteine (NAC), the oocytes developmental abnormalities, oxidative stress and apoptosis caused by Ca2+ overload were improved. In conclusion, our results indicated IP3R1 is required for meiotic progression and embryonic development by regulating mitochondrial calcium and oxidative damage.

Au-modified ceria nanozyme prevents and treats hypoxia-induced pulmonary hypertension with greatly improved enzymatic activity and safety

BackgroundDespite recent advances the prognosis of pulmonary hypertension remains poor and warrants novel therapeutic options. Extensive studies, including ours, have revealed that hypoxia-induced pulmonary hypertension is associated with high oxidative stress. Cerium oxide nanozyme or nanoparticles (CeNPs) have displayed catalytic activity mimicking both catalase and superoxide dismutase functions and have been widely used as an anti-oxidative stress approach. However, whether CeNPs can attenuate hypoxia-induced pulmonary vascular oxidative stress and pulmonary hypertension is unknown.ResultsIn this study, we designed a new ceria nanozyme or nanoparticle (AuCeNPs) exhibiting enhanced enzyme activity. The AuCeNPs significantly blunted the increase of reactive oxygen species and intracellular calcium concentration while limiting proliferation of pulmonary artery smooth muscle cells and pulmonary vasoconstriction in a model of hypoxia-induced pulmonary hypertension. In addition, the inhalation of nebulized AuCeNPs, but not CeNPs, not only prevented but also blunted hypoxia-induced pulmonary hypertension in rats. The benefits of AuCeNPs were associated with limited increase of intracellular calcium concentration as well as enhancement of extracellular calcium-sensing receptor (CaSR) activity and expression in rat pulmonary artery smooth muscle cells. Nebulised AuCeNPs showed a favorable safety profile, systemic arterial pressure, liver and kidney function, plasma Ca2+ level, and blood biochemical parameters were not affected.ConclusionWe conclude that AuCeNPs is an improved reactive oxygen species scavenger that effectively prevents and treats hypoxia-induced pulmonary hypertension.Graphical

Biodegradable Persistent Luminescence Nanoparticles as Pyroptosis Inducer for High-Efficiency Tumor Immunotherapy.

Pyroptosis possesses potent antitumor immune activity, making pyroptosis inducer development a promising direction for tumor immunotherapy. Persistent luminescence nanoparticles (PLNPs) are highly sensitive optical probes extensively employed in tumor diagnosis and therapy. However, a pyroptosis inducer based on PLNPs has not been reported yet. Herein, polyethylene glycol-poly lactic acid-co-glycolic acid (PEG-PLGA: PP) modified biodegradable CaS:Eu2+ (CSE@PP) PLNPs are synthesized as a pyroptosis inducer for tumor immunotherapy for the first time. The synthesized CSE@PP possesses biowindow persistent luminescence (PersL) and pH-responsive degradation properties, allowing it to remain stable under neutral pH but degrade when exposed to weak acid (pH< 6.5). During degradation within the tumor, CSE@PP constantly releases H2S and Ca2+ while its PersL gradually fades away. Thus, the PersL signal can self-monitor H2S and Ca2+ release. Furthermore, the released H2S and Ca2+ result in mitochondrial dysfunction and the inactivation of reactive oxygen species scavenging enzymes, synergistic facilitating intracellular oxidative stress, which induces caspase-1/GSDM-D dependent pyroptosis and subsequent antitumor immune responses. In a word, it is confirmed that CSE@PP can self-monitor H2S and Ca2+ release and pyroptosis-mediated tumor Immunotherapy. This work will facilitate biomedical applications of PLNPs and inspire pyroptosis-induced tumor immunotherapy.

Comparison of Growth and Metabolomic Profiles of Two Afforestation Cypress Species Cupressus chengiana and Platycladus orientalis Grown at Minjiang Valley in Southwest China.

In recent years, afforestation has been conducted in China's hot and dry valleys. However, there is still a paucity of knowledge regarding the performance of tree species in these semi-arid regions, particularly with regard to interspecies differences. The present study compares the growth and metabolome characteristics of two widely used cypress species, namely Cupressus chengiana and Platycladus orientalis, grown at two sites with distinct climate conditions in the hot and dry Minjiang Valley in southwestern China. The findings indicate that C. chengiana trees exhibit superior growth rates compared to P. orientalis trees at both study sites. In comparison to P. orientalis trees, C. chengiana trees demonstrated a greater tendency to close their stomata in order to prevent water loss at the hotter and drier site, Llianghekou (LHK). Additionally, C. chengiana trees exhibited significantly lower hydrogen peroxide levels than P. orientalis trees, either due to lower production and/or higher scavenging of reactive oxygen species. C. chengiana trees accumulated soluble sugars as well as sugar derivatives, particularly those involved in sucrose and galactose metabolisms under stressful conditions. The species-specific differences were also reflected in metabolites involved in the tricarboxylic acid cycle, nitrogen, and secondary metabolisms. The metabolome profiles of the two species appeared to be influenced by the prevailing climatic conditions. It appeared that the trees at the drier and hotter site, LHK, were capable of efficient nitrogen uptake from the soil despite the low soil nitrogen concentration. This study is the first to compare the growth performance and metabolic profiles of two widely used tree species with high resistance to adverse conditions. In addition to the species-specific differences and adaptations to different sites, the present study also provides insights into potential management strategies to alleviate abiotic stress, particularly with regard to nitrogen nutrients, in the context of climate change.

Inhaled tea polyphenol-loaded nanoparticles coated with platelet membranes largely attenuate asthmatic inflammation

BackgroundTea polyphenols (TPs), prominent constituents of green tea, possess remarkable antioxidant and anti-inflammatory properties. However, their therapeutic potential is limited due to low absorption and poor bioavailability. To address this limitation and enhance their efficacy, we developed a biomimetic nanoplatform by coating platelet membrane (PM) onto poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to create targeted delivery vehicles for TPs (PM@TP/NPs) to the inflamed tissues in asthma.MethodsAfter synthesizing and characterizing PM@TP/NPs, we assessed their biocompatibility and biosafety through cell viability assays, hemolysis tests, and inflammation analysis in vivo and in vitro. The therapeutic effect of PM@TP/NPs on asthma was then evaluated using a mouse model of HDM-induced asthma. Additionally, PM@TP/NPs-mediated reactive oxygen species (ROS) scavenging capacity, as well as the activation of signaling pathways, were analyzed in HBE cells and asthmatic mice via flow cytometry, RT-qPCR, and western blotting.ResultsCompared with free TPs, PM@TP/NPs demonstrated excellent biocompatibility and safety profiles in both in vitro and in vivo, as well as enhanced retention in inflamed lungs. In HDM-induced mouse asthma model, inhaled PM@TP/NPs largely attenuated lung inflammation and reduced the secretion of type 2 pro-inflammatory cytokines in the lungs compared to free TPs. The therapeutic effects of PM@TP/NPs on asthma might be associated with an enhanced ROS scavenging capacity, increased activation of the Nrf2/HO-1 pathway, and decreased activation of the CCL2/MAPK and TLR4/NF-κB pathway in the lungs.ConclusionsOur findings demonstrate that inhalation of PM@TP/NPs largely attenuated lung inflammation in HDM-induced asthmatic mice. These results suggest that PM@TP/NPs might be a novel therapeutic strategy for asthma.

Carbonized Polymer Dot-Tannic Acid Nanoglue: Tissue Reinforcement with Concurrent Fluorescent Tracking, Insulin Delivery, and Reactive Oxygen Species Regulation for Normal and Diabetic Wound Healing.

Nanotizing biosealant components offer a multitude of chemical functionalities for superior adhesion-cohesion, delivering unique properties for comprehensive wound healing that are otherwise impossible to achieve using commercial variants. For the first time, a two-step controlled hydrothermal pyrolysis is reported to nanotize dopamine, phloroglucinol, and glutaraldehyde into carbon dot (CD) to be subsequently converted into carbonized polymer dot (CPD) with gelatin as a co-substrate. Chemical crosslinking of CD with gelatin through Schiff base formation before the second pyrolysis step ensures a complex yet porous polymeric network. The retention of chemical functionalities indigenous to CD substrates and gelatin along with the preservation of CD photoluminescence in CPD for optical tracking is achieved. A unique nanoformulation is created with the CPD through tannic acid (TA) grafting evolving CPD-TA nanoglue demonstrating ≈1.32MPa strength in lap shear tests conducted on porcine skin, surpassing traditional bioadhesives. CPD-TA nanoglue uploaded insulin as chosen cargo disbursal at the wound site for healing normal and in vitro diabetic wound models using HEKa cells with extraordinary biocompatibility. Most importantly, CPD-TA can generate reactive oxygen species (ROS) and scavenge simultaneously under ambient conditions (23W white LED or dark) for on-demand sterilization or aiding wound recovery through ROS scavenging.

Study on the Function of SlWRKY80 in Tomato Defense against Meloidogyne incognita.

WRKY transcription factors (TFs) can participate in plant biological stress responses and play important roles. SlWRKY80 was found to be differentially expressed in the Mi-1- and Mi-3-resistant tomato lines by RNA-seq and may serve as a key node for disease resistance regulation. This study used RNAi to determine whether SlWRKY80 silencing could influence the sensitivity of 'M82' (mi-1/mi-1)-susceptible lines to M. incognita. Further overexpression of this gene revealed a significant increase in tomato disease resistance, ranging from highly susceptible to susceptible, combined with the identification of growth (plant height, stem diameter, and leaf area) and physiological (soluble sugars and proteins; root activity) indicators, clarifying the role of SlWRKY80 as a positive regulatory factor in tomato defense against M. incognita. Based on this phenomenon, a preliminary exploration of its metabolic signals revealed that SlWRKY80 stimulates different degrees of signaling, such as salicylic acid (SA), jasmonic acid (JA), and ethylene (ETH), and may synergistically regulate reactive oxygen species (ROS) accumulation and scavenging enzyme activity, hindering the formation of feeding sites and ultimately leading to the reduction of root gall growth. To our knowledge, SlWRKY80 has an extremely high utilization value for improving tomato resistance to root-knot nematodes and breeding.

CRISPR/Cas9-mediated genome editing of OsCS511 enhances cold tolerance in Oryza sativa L.

The frequency of climate change is increasing globally, which makes predictions challenging. Cold spells during the rice seedling stage can significantly reduce yield, prompting a constant need for cold-tolerant cultivars, which is a major breeding goal. However, the traditional crossbreeding of rice cultivars requires substantial time and effort. Recently, the application of CRISPR/Cas9 to reduce defects in elite cultivars has become a more cost-effective and time-efficient method for breeding cultivars than cross-breeding methods and can alleviate food insecurity. In the present study, CRISPR/Cas9-mediated genome editing was performed for OsCS511 a gene involved in cold susceptibility, identified using quantitative trait loci (QTL) mapping in Ilmi (Oryza sativa L. spp. Japonica cv. Ilmi). In Ilmi, CRISPR/Cas9 tool-edited OsCS511 homozygous lines were used in T0 and advanced generations in the field. CRISPR/Cas9 induced variations in the DNA sequence and plants with insertions or deletions compared to OsCS511 of Ilmi were selected as genome-edited lines. Agricultural traits, reactive oxygen species scavenging capacity, and stress-tolerance-related gene expression levels were evaluated under normal and cold stress conditions. Under normal conditions, all traits evaluated in the Ilmi and OsCS511 genome-edited lines exhibited similar results; however, when subjected to cold stress, the cold tolerance of OsCS511 genome-edited lines improved or reached the same level as that of Ilmi. OsCS511 genome-edited lines recovered and survived. From a breeding perspective, we suggest that CRISPR/Cas9 technology can precisely reduce defects in existing superior rice cultivars with high efficiency and speed.

Melatonin-coated nanofiber cell sheets promote periodontal regeneration through ROS scavenging and preservation of stemness

Mesenchymal stem cell (MSC)-based cell sheet engineering holds great promise for periodontal tissue engineering and restoring damaged tissues. However, achieving optimal regenerative outcomes remains a challenge. This study introduces a novel approach that integrates melatonin-coated nanofiber fragments (mNFs) into dental follicle stem cell sheets (mNF-CSs) to enhance their regenerative potential. The mNF-CSs were engineered using electrospun poly-L-lactic acid (PLLA) nanofiber sheets fragmented into mNFs and coated with melatonin, a potent antioxidant and osteogenic agent. The mNF-CSs exhibited a homogenous morphology with sustained melatonin release over 21 days, providing a prolonged antioxidative effect critical for tissue regeneration. In vitro experiments demonstrated that mNF-CSs significantly reduced intracellular reactive oxygen species (ROS) levels and upregulated antioxidative proteins such as SOD1 and SOD2, resulting in improved cell viability, maintenance of stemness, and enhanced osteogenic differentiation potential of dental follicle stem cells (DFCs). In vivo studies using both a nude mouse and a rat periodontal defect model demonstrated that mNF-CSs promoted alveolar bone repair and periodontal tissue regeneration, with enhanced retention of MSCs at the defect site and increased expression of periodontal tissue-related markers. Transcriptome analysis revealed the upregulation of genes associated with biomineralization, odontogenesis, and autophagy pathways in mNF-CSs, suggesting their ability to modulate crucial cellular processes for tissue regeneration. Overall, mNF-CSs offer a promising strategy for enhancing periodontal tissue engineering applications, providing a platform for improving bone grafts and regenerative medicine strategies in the context of periodontal diseases.

Synthesis and Anticancer Evaluation of Disubstituted Benzimidazoles via One-Pot Telescopic Grinding Approach.

Benzimidazole compounds are known for their broad spectrum therapeutic potentials. A small library of benzimidazole derivatives were designed and synthesized via a one-pot telescopic grinding approach. The ability of these molecules as proposed anticancer agents were evaluated by their potential to bind to two important cancer pathway protein targets, human estrogen receptors and cyclin dependant kinases, 3ERT and 5FGK respectively. Further nucleic acid binding and reactive oxygen species (ROS) scavenging capacity being in the scope for anticancer potential evaluations, the ability of these molecules have been evaluated for the same. Further, to support the experimental and computational results, AI-assisted tools were employed to predict the anticancer activity (PASS) as well as to identify false positives (PAINS). Also, the druggability of the proposed compounds was evaluated by following their pharmacokinetic parameters - ADME.

Biomineralized MnO2 Nanoparticle-Constituted Hydrogels Promote Spinal Cord Injury Repair by Modulating Redox Microenvironment and Inhibiting Ferroptosis.

Spinal cord injury (SCI) is one of the most severe injuries, characterized by multiple positive feedback regulatory signaling networks formed by oxidative stress and inflammation in the injury microenvironment, leading to neuronal cell damage and even death. Here, astragaloside IV (AS), known for its regulatory role in ferroptosis, was encapsulated in the cavity of apoferritin (HFn) after an in situ biomineralization process involving MnO2, resulting in the synthesis of HFn@MnO2/AS nanoparticles. These nanoparticles were then dispersed in chitosan/polyvinyl alcohol/glutaraldehyde/sodium β-glycerophosphate (CGPG) hydrogels to form CGPG-HFn@MnO2/AS injectable thermosensitive hydrogels that can scavenge reactive oxygen species (ROS) in the microenvironment. Our findings indicated that the prepared CGPG-HFn@MnO2/AS hydrogel exhibited remarkable efficacy in scavenging ROS in vitro, effectively ameliorating the oxidative stress microenvironment post-SCI. Furthermore, it inhibited oxidative stress-induced ferroptosis in vitro and in vivo by regulating SIRT1 signaling, thereby promoting neuronal cell migration and repair. Hence, the developed hydrogel combining MnO2 and AS exhibited multifaceted abilities to modulate the pathological microenvironment, providing a promising therapeutic strategy for central nervous system (CNS) diseases.

Neutrophil membrane-derived nanoparticles protect traumatic brain injury via inhibiting calcium overload and scavenging ROS

The secondary injury is more serious after traumatic brain injury (TBI) compared with primary injury. Release of excessive reactive oxygen species (ROS) and Ca2+ influx at the damaged site trigger the secondary injury. Herein, a neutrophil-like cell membrane-functionalized nanoparticle was developed to prevent ROS-associated secondary injury. NCM@MP was composed of three parts: (1) Differentiated neutrophil-like cell membrane (NCM) was synthesized, with inflammation-responsive ability to achieve effective targeting and to increase the retention time of Mn3O4 and nimodipine (MP) in deep injury brain tissue via C-X-C chemokine receptor type 4, integrin beta 1 and macrophage antigen-1. (2) Nimodipine was used to inhibit Ca2+ influx, eliminating the ROS at source. (3) Mn3O4 further eradicated the existing ROS. In addition, NCM@MP also exhibited desirable properties for T1 enhanced imaging and low toxicity which may serve as promising multifunctional nanoplatforms for precise therapies. In our study, NCM@MP obviously alleviated oxidative stress response, reduced neuroinflammation, protected blood–brain barrier integrity, relieved brain edema, promoted the regeneration of neurons, and improved the cognition of TBI mice. This study provides a promising TBI management to relieve the secondary spread of damage.Graphical

Metabolic reprogramming of poly(morpho)nuclear giant cells determines glioblastoma recovery from doxorubicin-induced stress

BackgroundMulti-drug resistance of poly(morpho)nuclear giant cells (PGCs) determines their cytoprotective and generative potential in cancer ecosystems. However, mechanisms underlying the involvement of PGCs in glioblastoma multiforme (GBM) adaptation to chemotherapeutic regimes remain largely obscure. In particular, metabolic reprogramming of PGCs has not yet been considered in terms of GBM recovery from doxorubicin (DOX)-induced stress.MethodsLong-term proteomic and metabolic cell profiling was applied to trace the phenotypic dynamics of GBM populations subjected to pulse DOX treatment in vitro, with a particular focus on PGC formation and its metabolic background. The links between metabolic reprogramming, drug resistance and drug retention capacity of PGCs were assessed, along with their significance for GBM recovery from DOX-induced stress.ResultsPulse DOX treatment triggered the transient formation of PGCs, followed by the appearance of small expanding cell (SEC) clusters. Development of PGCs was accompanied by the mobilization of their metabolic proteome, transient induction of oxidative phosphorylation (OXPHOS), and differential intracellular accumulation of NADH, NADPH, and ATP. The metabolic background of PGC formation was confirmed by the attenuation of GBM recovery from DOX-induced stress following the chemical inhibition of GSK-3β, OXPHOS, and the pentose phosphate pathway. Concurrently, the mobilization of reactive oxygen species (ROS) scavenging systems and fine-tuning of NADPH-dependent ROS production systems in PGCs was observed. These processes were accompanied by perinuclear mobilization of ABCB1 and ABCG2 transporters and DOX retention in the perinuclear PGC compartments.ConclusionsThese data demonstrate the cooperative pattern of GBM recovery from DOX-induced stress and the crucial role of metabolic reprogramming of PGCs in this process. Metabolic reprogramming enhances the efficiency of self-defense systems and increases the DOX retention capacity of PGCs, potentially reducing DOX bioavailability in the proximity of SECs. Consequently, the modulation of PGC metabolism is highlighted as a potential target for intervention in glioblastoma treatment.

Cost-effective and natural-inspired lotus root/GelMA scaffolds enhanced wound healing via ROS scavenging, angiogenesis and reepithelialization

Skin wounds, prevalent and fraught with complications, significantly impact individuals and society. Wound healing encounters numerous obstacles, such as excessive reactive oxygen species (ROS) production and impaired angiogenesis, thus promoting the development of chronic wound. Traditional clinical interventions like hemostasis, debridement, and surgery face considerable challenges, including the risk of secondary infections. While therapies designed to scavenge excess ROS and enhance proangiogenic properties have shown effectiveness in wound healing, their clinical adoption is hindered by high costs, complex manufacturing processes, and the potential for allergic reactions. Lotus root, distinguished by its natural micro and macro porous architecture, exhibits significant promise as a tissue engineering scaffold. This study introduced a novel scaffold based on hybridization of lotus root-inspired and Gelatin Methacryloyl (GelMA), verified with satisfactory physicochemical properties, biocompatibility, antioxidative capabilities and proangiogenic abilities. In vivo tests employing a full-thickness wound model revealed that these scaffolds notably enhanced micro vessel formation and collagen remodeling within the wound bed, thus accelerating the healing process. Given the straightforward accessibility of lotus roots and the cost-effective production of the scaffolds, the novel scaffolds with ROS scavenging, pro-angiogenesis and re-epithelialization abilities are anticipated to have clinical applicability for various chronic wounds.

Nano-Fe3O4: Enhancing the tolerance of Elymus nutans to Cd stress through regulating programmed cell death

Cadmium (Cd) poses a significant threat to plant growth and the environment. Nano-Fe3O4 is effective in alleviating Cd stress in plants. Elymus nutans Griseb. is an important fodder crop on the Qinghai-Tibetan Plateau (QTP). However, the potential mechanism by which nano-Fe3O4 alleviates Cd stress in E. nutans is not well understood. E. nutans were subjected to single Cd, single nano-Fe3O4, and co-treatment with nano-Fe3O4 and Cd, and the effects on morphology, Cd uptake, antioxidant enzyme activity, reactive oxygen species (ROS) levels and programmed cell death (PCD) were studied to clarify the regulatory mechanism of nano-Fe3O4. The results showed that Cd stress significantly decreased the germination percentage and biomass of E. nutans. The photosynthetic pigment content decreased significantly under Cd stress. Cd stress also caused oxidative stress and lipid peroxidation, accumulation of excessive ROS, resulting in PCD, but the effect of nano-Fe3O4 was different. Seed germination, seedling growth, and physiological processes were analyzed to elucidate the regulatory role of nano-Fe3O4 nanoparticles in promoting photosynthesis, reducing Cd accumulation, scavenging ROS, and regulating PCD, to promote seed germination and seedling growth in E. nutans. This report provides a scientific basis for improving the tolerance of Elymus to Cd stress by using nano-Fe3O4.

Comparative Metabolome and Transcriptome Analysis of Rapeseed (Brassica napus L.) Cotyledons in Response to Cold Stress.

Cold stress affects the seed germination and early growth of winter rapeseed, leading to yield losses. We employed transmission electron microscopy, physiological analyses, metabolome profiling, and transcriptome sequencing to understand the effect of cold stress (0 °C, LW) on the cotyledons of cold-tolerant (GX74) and -sensitive (XY15) rapeseeds. The mesophyll cells in cold-treated XY15 were severely damaged compared to slightly damaged cells in GX74. The fructose, glucose, malondialdehyde, and proline contents increased after cold stress in both genotypes; however, GX74 had significantly higher content than XY15. The pyruvic acid content increased after cold stress in GX74, but decreased in XY15. Metabolome analysis detected 590 compounds, of which 32 and 74 were differentially accumulated in GX74 (CK vs. cold stress) and XY15 (CK vs. cold stressed). Arachidonic acid and magnoflorine were the most up-accumulated metabolites in GX74 subjected to cold stress compared to CK. There were 461 and 1481 differentially expressed genes (DEGs) specific to XY15 and GX74 rapeseeds, respectively. Generally, the commonly expressed genes had higher expressions in GX74 compared to XY15 in CK and cold stress conditions. The expression changes in DEGs related to photosynthesis-antenna proteins, chlorophyll biosynthesis, and sugar biosynthesis-related pathways were consistent with the fructose and glucose levels in cotyledons. Compared to XY15, GX74 showed upregulation of a higher number of genes/transcripts related to arachidonic acid, pyruvic acid, arginine and proline biosynthesis, cell wall changes, reactive oxygen species scavenging, cold-responsive pathways, and phytohormone-related pathways. Taken together, our results provide a detailed overview of the cold stress responses in rapeseed cotyledons.

Mesoporous zinc-polyphenol nanozyme for attenuating renal ischemia-reperfusion injury.

Aim: To target the reactive oxygen species (ROS) accumulation and renal tubular epithelial cell (rTEC) death in renal ischemia-reperfusion injury (IRI), we constructed a nanoparticle that offers ROS scavenging and rTEC-death inhibition: mesoporous zinc-tannic acid nanozyme (ZnTA). Materials & methods: After successfully constructing ZnTA, we proceeded to examine its effect on ROS accumulation, cellular ferroptosisand apoptosis, as well as injury severity. Results: Malondialdehyde, Fe2+ amounts and 4-HNE staining demonstrated that ZnTA effectively attenuated rTEC ferroptosis. TUNEL staining confirmed that Zn2+ carried by ZnTA could effectively inhibit caspase 3 and caspase 9, mitigating apoptosis. Finally, it reduced renal IRI through the synergistic effect of ROSscavenging and cell-death inhibition. Conclusion: This study is expected to provide a paradigm for a combined therapeutic strategy for renal IRI.

Melatonin and copper oxide nanoparticles synergistically mitigate clubroot disease and enhance growth dynamics in Brassica rapa

Clubroot, a devastating soil borne disease affecting 30%∼50% of Brassicaceae crops worldwide, lacks effective control measures. In the present study, we explored the potential of melatonin (MT) and copper oxide nanoparticle (CuO-NPs) in mitigating clubroot severity in the Brassica rapa ssp. pekinensis. Following 18 h priming with MT, CuO-NPs, or both seeds were grown in controlled environment using synthetic potting mix. Inoculated with Plasmodiophora brassicae spores on 5th day, followed by a soil drench phyto-nano treatment with a week interval. Plants were assessed for various health and growth indices including disease, biometrics, photosynthesis, reactive oxygen species (ROS), antioxidant enzyme activity, hormones and genes expression at onset of secondary clubroot infection using established protocols. Statistical analysis employed ANOVA with Fisher's LSD for significance assessment (P < 0.05). Our results revealed that seed priming with both MT (50 μMol/L) and CuO-NPs (200 mg/L), followed by soil drenching significantly reduced clubroot incidence (38%) and disease index (57%), compared to control treatments. This synergistic effect was associated with enhanced plant growth (shoots: 48% and roots: 59%). Plants treated with both MT and CuO-NPs showed robust antioxidant defenses, significantly increased superoxide dismutase (SOD (25/29%)), catalase (CAT (83/55%)), and ascorbate peroxidase (APX (83/46%)) activity in both shoots/roots, respectively, compared to infected control. Notably, salicylic acid and jasmonic acid levels doubled in treated plants, while stress hormone abscisic acid (ABA) decreased by 80% in roots and 21% in shoots. Gene expression analysis corroborated these findings, showing that the combined treatment activated antioxidant defense genes (SOD, APX and CAT) by 1.9–7.2-fold and upregulated hormone signaling genes JAZ1 (7.8-fold), MYC2 (3.9-fold) and SABP2 (36-fold). Conversely, ABA biosynthesis genes (ABA1 and NCED1) were downregulated up to 7.2-fold, while plant resistance genes NPR1, PRB1 and PDF1.2 were dramatically increased by up to 6.3-fold compared to infected plants. Overall, our combined treatment approach significantly reduces clubroot severity in B. rapa via enhanced antioxidant defenses, improved ROS scavenging, coordinated hormonal regulation and increased pathogen response genes. This study offers promising strategy for developing effective control measures against clubroot in susceptible cruciferous crops.

Role of ROS and autophagy in the pathological process of atherosclerosis.

Activation of autophagy and production of reactive oxygen species occur at various stages of atherosclerosis.To clarify the role and mechanism of autophagy and reactive oxygen species in atherosclerosis is of great significance to the prevention and treatment of atherosclerosis.Recent studies have shown that basal autophagy plays an important role in protecting cells from oxidative stress, reducing apoptosis and enhancing atherosclerotic plaque stability.Autophagy deficiency and excessive accumulation of reactive oxygen species can impair the function of endothelial cells, macrophages and smooth muscle cells, trigger autophagic cell death, and lead to instability and even rupture of plaques. However, the main signaling pathways regulating autophagy, the molecular mechanisms of autophagy and reactive oxygen species interaction, how they are initiated and distributed in plaques, and how they affect atherosclerosis progression, remain to be clarified.At present, there is no autophagy inducer used to treat atherosclerosis clinically.Therefore, it is urgent to clarify the mechanism of autophagy and find new targets for autophagy. Antioxidant agents generally have defects such as low reactive oxygen species scavenging efficiency and high cytotoxicity. Highly potent autophagy inducers and reactive oxygen species scavengers still need to be further developed and validated to provide more possibilities for innovative treatments for atherosclerosis.

Mesoporous manganese-doped nano-antioxidant suppresses pyroptosis for effective ischemic stroke therapy

Pyroptosis mediates neuroinflammation following ischemic stroke and contributes to its development, indicating that targeting pyroptosis-related pathways could be a potential therapeutic strategy for stroke. In this study, a mesoporous manganese-doped cerium oxide (MMC) nano-antioxidant encapsulated with caspase-1 inhibitor VX765 is rationally designed and engineered to relieve ischemic stroke by integrating the suppression of pyroptosis activity with reactive oxygen species (ROS) scavenging capability. Through the surface modification of Angiopoietin-2 (Ang2), the nano-antioxidant can specifically bind to the low-density lipoprotein receptor-related protein, cross the blood–brain barrier, and ultimately aggregate in ischemic neuronal tissues. In mice subjected to middle cerebral artery occlusion/reperfusion, the nano-antioxidant alleviates oxidative stress, inhibits cell pyroptosis, reduces inflammatory cytokines, and regulates microglial polarization toward M2, ultimately mitigating neuroinflammation and reperfusion injury in brain tissue. Mechanistic studies reveal that the pyroptosis-associated NOD-like receptor signaling pathway, the inflammation-associated TNF signaling pathway, the neutrophil chemotaxis-associated Toll-like receptor signaling pathway, and the oxidative stress-associated NF-kappa B signaling pathway are involved in the antioxidant-mediated stroke therapy. Endowed with pyroptosis-reversing ability and nano-antioxidant activities, this engineered antioxidant presents a novel therapeutic paradigm for minimizing reperfusion injury and enhancing stroke treatment efficacy.