Intracellular Antioxidant System Research Articles

Morin Reactivates Nrf2 by Targeting Inhibition of Keap1 to Alleviate Deoxynivalenol-Induced Intestinal Oxidative Damage

As a prevalent mycotoxin found in cereal foods and feed, deoxynivalenol (DON) disrupts the orderly regeneration of intestinal epithelial tissue by interfering with the intracellular antioxidant defense system. However, the potential of mulberry leaf-derived Morin, a natural flavonoid active substance with clearing reactive oxygen species (ROS), to mitigate DON-induced intestinal oxidative damage remains unclear. Our investigation demonstrates that Morin effectively reverses the decline in growth performance and repairs damaged jejunal structures and barrier function under DON exposure. Furthermore, the proliferation and differentiation of intestinal stem cells (ISCs) is enhanced significantly after Morin intervention. Importantly, Morin increases the levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in the serum and jejunal tissue, while reducing the accumulation of ROS and malondialdehyde (MDA). Molecular interaction analysis further confirms that Morin targets inhibition of Keap1 to activate the Nrf2-mediated antioxidant system. In summary, our results suggest that Morin alleviates the oxidative damage induced by DON by regulating the Keap1/Nrf2 pathway, thereby restoring the proliferation and differentiation activity of ISC, which provides new insights into Morin mitigating DON damage.

Silencing superoxide dismutases (SOD1&SOD2) potentiates ROS-induced apoptosis in chordoma cells.

Chordoma, characterized as a slow growing yet locally invasive and destructive bone tumor mainly emerging in the sacrum and clivus, presents a unique challenge due to its rarity, hampering the development of effective treatment strategies. Comprehensive understanding of tumor biology is crucial to suggest novel treatment modalities. Reactive oxygen species (ROS), a family of chemically reactive and unstable oxygen derivatives, are controlled by an intracellular antioxidant system to maintain homeostasis. Higher doses of ROS levels have been associated with the oxidative stress-induced tumor cell death, highlighting the potential of fine-tuning ROS regulation as a target for cancer therapies. The association of ROS mechanism and chordoma remains to be elucidated. In this study, we investigated the effect of targeting the ROS mechanism in chordoma, focusing on superoxide dismutase 1 and superoxide dismutase 2. Two different chordoma datasets were used to assess oxidative stress-related genes. ROS levels and mitochondrial membrane potential (mtMP) in chordoma cells were measured. The gene expression levels of SOD1 and SOD2 in chordoma patients were also evaluated. SOD2 and SOD1 targeted siRNAs were used to silence gene expression in chordoma cells, and quantitative real-time PCR (qRT-PCR) was used to compare gene expression levels. Apoptotic cell populations were determined using flow cytometry. The levels of ROS and mtMP were increased in chordoma cell lines compared to healthy nucleus pulposus cells. The chordoma omics data showed induced levels of SOD2. Chordoma tissues also showed high levels of the SOD2 gene. Silencing SOD2 and combined silencing of SOD2 and SOD1 expression increased ROS levels or mtMP, and both induced apoptosis in chordoma cells. ROS imbalance plays a role in chordoma pathogenesis. SOD2 and SOD1 might be key enzymes in chordoma to modulate ROS levels, and inhibiting the SOD2 and SOD1 activity might be a potential therapeutic target for chordoma treatment.

Bioinspired artificial antioxidases for efficient redox homeostasis and maxillofacial bone regeneration

Reconstructing large, inflammatory maxillofacial defects using stem cell-based therapy faces challenges from adverse microenvironments, including high levels of reactive oxygen species (ROS), inadequate oxygen, and intensive inflammation. Here, inspired by the reaction mechanisms of intracellular antioxidant defense systems, we propose the de novo design of an artificial antioxidase using Ru-doped layered double hydroxide (Ru-hydroxide) for efficient redox homeostasis and maxillofacial bone regeneration. Our studies demonstrate that Ru-hydroxide consists hydroxyls-synergistic monoatomic Ru centers, which efficiently react with oxygen species and collaborate with hydroxyls for rapid proton and electron transfer, thus exhibiting efficient, broad-spectrum, and robust ROS scavenging performance. Moreover, Ru-hydroxide can effectively sustain stem cell viability and osteogenic differentiation in elevated ROS environments, modulating the inflammatory microenvironment during bone tissue regeneration in male mice. We believe this Ru-hydroxide development offers a promising avenue for designing antioxidase-like materials to treat various inflammation-associated disorders, including arthritis, diabetic wounds, enteritis, and bone fractures.

Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide‐induced Nephrotoxicity and Urotoxicity in Rats

To evaluate kefir, a naturally occurring fermented dairy product, with pharmacological and therapeutic qualities including antioxidant, anti-apoptotic, and anti-inflammatory effects against cyclophosphamide (CP)-induced hemorrhagic cystitis and nephrotoxicity in rats. For this purpose, experimental rats were divided into 6 groups; control (Group 1), 150 mg/kg CP (Group 2), 5 mg/kg kefir (Group 3), l0 mg/kg kefir (Group 4), 5 mg/kg kefir+150 CP (Group 5), l0 mg/kg kefir+150 CP (Group 6). Since there was no difference in kefirs fermented on different days, kefirs from the 1st, 2nd, and 3rd days were mixed and given to the rats for 12 days, while CP was given as an only dose and i.p. on the 12th day of the experiment. Histologic evaluations revealed that CP caused toxicity in kidney and bladder. On the other hand, biochemical evaluations showed a significant increase in serum blood urea nitrogen (BUN) and creatinine (Cre) levels, which are tissue toxicity markers, and a significant decrease in catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, which are intracellular antioxidant system markers, in the CP-treated experimental group. However, all values were reversed as a result of kefir (5 and 10 mg/kg) treatment. These results showed that kefir is an effective protective agent against CP-induced hemorrhagic cystitis and nephrotoxicity.

Transcriptome Analysis Provides Insights into the Mechanism of the Transcription Factor AaCrz1 Regulating the Infection Structure Formation of Alternaria alternata Induced by Pear Peel Wax Signal.

Alternaria alternata, a causal agent of pear black spot, can recognize and respond to physicochemical signals from fruit surfaces through an intricate signaling network to initiate infection. Crz1 is an important transcription factor downstream of the calcium signaling pathway. In this study, we first investigated the infection structure formation process of the wild type (WT) and ΔAaCrz1 strains induced by the cuticular wax of the "Zaosu" pear by microscopic observation. We found that the infection process was delayed and the rate of appressorium formation and infection hyphae formation was significantly decreased in the ΔAaCrz1 strain. RNA-seq of WT and ΔAaCrz1 strains was analyzed after 6 h of induction with pear wax. A total of 893 up-regulated and 534 down-regulated genes were identified. Among them, genes related to cell wall degrading enzymes, ABC transporters, and ion homeostasis were down-regulated, and the autophagy pathway was induced and activated. In addition, disruption to the intracellular antioxidant system was also found after AaCrz1 knockdown. In summary, this study provides new information on the mechanism of the transcription factor AaCrz1 in the regulation of infection structure formation of A. alternata induced by pear peel wax signal, which can be used to develop new strategies for controlling fungal diseases in the future.

Mitochondrial Dysfunction Associated with mtDNA Mutation: Mitochondrial Genome Editing in Atherosclerosis Research.

Atherosclerosis is a complex cardiovascular disease often associated with mitochondrial dysfunction, which can lead to various cellular and metabolic abnormalities. Within the mitochondrial genome, specific mutations have been implicated in contributing to mitochondrial dysfunction. Atherosclerosis-associated m.15059G>A mutation has been of particular interest due to its potential role in altering mitochondrial function and cellular health. This study aims to investigate the role of the atherosclerosis-associated m.15059G>A mutation in the development of mitochondrial dysfunction in monocyte-- like cells. Monocyte-like cytoplasmic hybrid cell line TC-HSMAM1, which contains the m.15059G>A mutation in mtDNA, was used. The MitoCas9 vector was utilized to eliminate mtDNA copies carrying the m.15059G>A mutation from TC-HSMAM1 cybrids. Mitochondrial membrane potential, generation of reactive oxygen species, and lipid peroxidation levels were assessed using flow cytometry. Cellular reduced glutathione levels were assessed using the confocal microscopy. The oxygen consumption rate was measured using polarographic oxygen respirometry. The elimination of the m.15059G>A mutation resulted in a significant increase in mitochondrial membrane potential and improved mitochondrial efficiency while also causing a decrease in the generation of reactive oxygen species, lipid peroxidation, as well as cellular bioenergetic parameters, such as proton leak and non-mitochondrial oxygen consumption. At the same time, no changes were found in the intracellular antioxidant system after the mitochondrial genome editing. The presence of the m.15059G>A mutation contributes to mitochondrial dysfunction by reducing mitochondrial membrane potential, increasing the generation of reactive oxygen species and lipid peroxidation, and altering mitochondrial bioenergetics. Elimination of the mtDNA containing atherogenic mutation leads to an improvement in mitochondrial function.

Intracellular Iron Deficiency and Abnormal Metabolism, Not Ferroptosis, Contributes to Homocysteine-Induced Vascular Endothelial Cell Death.

Background/Objectives: Homocysteine (Hcy) and iron are factors co-related with the progression of cardiovascular diseases. The vascular endothelium is an important barrier for physiological homeostasis, and its impairment initiates cardiovascular injury. However, the mechanism underlying Hcy-caused vascular endothelial cell injury and the participation of iron are not fully elucidated. This study aims to investigate the Hcy-induced vascular endothelial injury and iron metabolism dysfunction as well as the underlying molecular mechanism. Methods: Human umbilical vein endothelial cells (HUVECs) were employed as the experimental model to examine the Hcy-induced endothelial injury and its underlying mechanism via various biochemical assays. Results: Hcy suppressed the cell viability and proliferation and caused cell death in a concentration-dependent manner. Hcy induced cell cycle arrest, apoptosis, and autophagy as well as impairment of intracellular energy metabolism. Hcy disrupted the intracellular antioxidant system and mitochondrial function by increasing intracellular ROS, MDA and mitochondrial content, and decreasing the SOD activity and mitochondrial membrane potential. Hcy significantly reduced the GSH-Px activity along with the accumulation of intracellular GSH in a concentration-dependent manner. Ferroptosis inhibitors, Ferrostatin-1 (Fer-1), and Deferoxamine (DFO) significantly decreased the Hcy-caused cytotoxicity accompanied by a reduction in dysregulated mitochondria content, but only DFO ameliorated the elevation of intracellular ROS, and neither Fer-1 nor DFO affected the Hcy-caused reduction in intracellular ATP. In addition, Hcy decreased the intracellular concentration of iron, and supplementing Hcy with various concentrations of Fe3+ increased the cell viability and decreased the LDH release in a concentration-dependent manner. Hcy dramatically decreased the mRNA expression level of transferrin receptor while increasing the mRNA expression levels of transferrin, ferritin light chain, ferritin heavy chain, ferroportin, and SLC7A11. Moreover, Hcy suppressed the protein expression of phospho-Akt, phospho-mTOR, Beclin-1, LC3A/B, Nrf2, HO-1, phospho-MEK1/2, phospho-ERK1/2, and Caspase-3 in concentration- and time-dependent manners. Conclusions: Hcy-induced vascular endothelial injury is likely to be associated with apoptosis and autophagy, but not ferroptosis. The key underlying mechanisms are involved in the disruption of the intracellular antioxidant system and iron metabolism via regulation of PI3K/Akt/mTOR, MAPKs, Nrf2/HO-1, and iron metabolism.

The protective effects of selenium and boron on cyclophosphamide-induced hepatic oxidative stress, inflammation, and apoptosis in rats

Cyclophosphamide (CP) is an alkylating anticancer drug with broad clinical application that is highly effective in the treatment of cancer and non-malignant diseases. However, the main limiting effect of CP is multi-organ toxicity due to damage to normal tissues. The aim of this study is to compare the hepatoprotective potential of selenium (Se) and boron (B) in CP-induced liver injury in experimental rats. The rats were randomly divided into six equal groups: Control (saline), 200 mg/kg CP (administered once on the fourth day of the experiment), 1.5 mg/kg Se (administered once/time daily for 6 days), 20 mg/kg B (administered once/time daily for 6 days), Se + CP and B + CP administered intraperitoneally (i.p.). Administration of CP leads to an increase in the levels of apoptotic markers (Bax, caspase-3), the apoptotic signaling pathway (Nrf2), oxidative stress indicators (TOS, OSI), lipid peroxidation markers (MPO, MDA), inflammation levels (NF-kB, TNF-α, IL-1β, IL -6), liver function markers (ALT, AST, ALP), while apoptosis markers (Bcl-2), apoptosis pathway (Keap-1), oxidative stress indicator (TAS), inflammation (IL -10) and intracellular antioxidant defense system (SOD, CAT, GPx and GSH) decreased. In addition, degeneration of hepatocytes and congestion in the central veins were observed. In contrast, in the groups administered Se and B with CP, the changes that occurred were reversed. However, it was found that Se protects the liver slightly better against CP damage than B. The protective effect of Se and B against the toxic effects of CP on the antioxidant markers SOD, CAT and GPx1 was also investigated in silico. The in silico results were consistent with the in vivo results for SOD and CAT, but not for GPx1.

Ferroptosis: Regulatory mechanisms and potential targets for bone metabolism: A review.

Bone homeostasis is a homeostasis process constructed by osteoblast bone formation and osteoclast bone resorption. Bone homeostasis imbalance and dysfunction are the basis for the development of various orthopedic diseases such as osteoporosis, osteoarthritis, and steroid-induced avascular necrosis of femoral head. Previous studies have demonstrated that ferroptosis can induce lipid peroxidation through the generation of reactive oxygen species, activate a number of signaling pathways, and participate in the regulation of osteoblast bone formation and osteoclast bone resorption, resulting in bone homeostasis imbalance, which is an important factor in the pathogenesis of many orthopedic diseases, but the mechanism of ferroptosis is still unknown. In recent years, it has been found that, in addition to iron metabolism and intracellular antioxidant system imbalance, organelle dysfunction is also a key factor affecting ferroptosis. This paper takes this as the starting point, reviews the latest literature reports at home and abroad, elaborates the pathogenesis and regulatory pathways of ferroptosis and the relationship between ferroptosis and various organelles, and summarizes the mechanism by which ferroptosis mediates bone homeostasis imbalance, with the aim of providing new directions for the research related to ferroptosis and new ideas for the prevention and treatment of bone and joint diseases.

Hydroxyethyl starch conjugates co-assembled nanoparticles promote photodynamic therapy and antitumor immunity by inhibiting antioxidant systems

Photodynamic therapy (PDT) can produce high levels of reactive oxygen species (ROS) to kill tumor cells and induce antitumor immunity. However, intracellular antioxidant systems, including glutathione (GSH) system and thioredoxin (Trx) system, limit the accumulation of ROS, resulting in compromised PDT and insufficient immune stimulation. Herein, we designed a nanomedicine PtHPs co-loading photosensitizer pyropheophorbide a (PPa) and cisplatin prodrug Pt–COOH(IV) (Pt (IV)) based on hydroxyethyl starch (HES) to inhibit both GSH and Trx antioxidant systems and achieve potent PDT as well as antitumor immune responses. Specifically, HES-PPa and HES-Pt were obtained by coupling HES with PPa and Pt (IV), and assembled into nanoparticle PtHPs by emulsification method to achieve the purpose of co-delivery of PPa and Pt (IV). PtHPs improved PPa photostability while retaining PPa photodynamic properties. In vitro experiments showed that PtHPs reduced GSH, inhibited Trx system and had better cell-killing effect and ROS generation ability. Subcutaneous tumor models showed that PtHPs had good safety and tumor inhibition effect. Bilateral tumor models suggested that PtHPs promoted the release of damage-associated molecular patterns and the maturation of dendritic cells, induced T cell-mediated immune responses, and thus suppressed the growth of both primary and distal tumors. This study reports a novel platinum-based nanomedicine and provides a new strategy for boosting PDT therapy-mediated antitumor immunity by overcoming intrinsic antioxidant systems.

Exploring the Neuroprotective Potential of Desmodium Species: Insights into Radical Scavenging Capacity and Mechanisms against 6-OHDA-Induced Neurotoxicity.

In this study, we collected seven prevalent Taiwanese Desmodium plants, including three species with synonymous characteristics, in order to assess their antioxidant phytoconstituents and radical scavenging capacities. Additionally, we compared their inhibitory activities on monoamine oxidase (MAO) and 6-hydroxydopamine (6-OHDA) auto-oxidation. Subsequently, we evaluated the neuroprotective potential of D. pulchellum on 6-OHDA-induced nerve damage in SH-SY5Y cells and delved into the underlying neuroprotective mechanisms. Among the seven Desmodium species, D. pulchellum exhibited the most robust ABTS radical scavenging capacity and relative reducing power; correspondingly, it had the highest total phenolic and phenylpropanoid contents. Meanwhile, D. motorium showcased the best hydrogen peroxide scavenging capacity and, notably, D. sequax demonstrated remarkable prowess in DPPH radical and superoxide scavenging capacity, along with selective inhibitory activity against MAO-B. Of the aforementioned species, D. pulchellum emerged as the frontrunner in inhibiting 6-OHDA auto-oxidation and conferring neuroprotection against 6-OHDA-induced neuronal damage in the SH-SY5Y cells. Furthermore, D. pulchellum effectively mitigated the increase in intracellular ROS and MDA levels through restoring the activities of the intracellular antioxidant defense system. Therefore, we suggest that D. pulchellum possesses neuroprotective effects against 6-OHDA-induced neurotoxicity due to the radical scavenging capacity of its antioxidant phytoconstituents and its ability to restore intracellular antioxidant activities.

Insight into the surface discharge cold plasma efficient inactivation of Pseudomonas fluorescens in water based on exogenous reactive oxygen and nitrogen species: Synergistic mechanism and energy benefits

As well known, surface discharge cold plasma has efficient inactivation ability and a variety of RONS are main active particles for inactivation, but their synergistic mechanism is still not clear. Therefore, surface discharge cold plasma system was applied to treat Pseudomonas fluorescens to study bacterial inactivation mechanism and energy benefit. Results showed that energy efficiency was directly proportional to applied voltage and inversely proportional to initial concentration. Cold plasma treatment for 20 min was inactivated by approximately > 4-log10Pseudomonas fluorescens and application of •OH and 1O2 scavengers significantly improved survival rate. In addition, •OH and 1O2 destroyed cell membrane structure and membrane permeability, which promoted diffusion of RONS into cells and affecting energy metabolism and antioxidant capacity, leading to bacterial inactivation. Furthermore, accumulation of intracellular NO and ONOOH was related to infiltration of exogenous RNS, while accumulation of •OH, H2O2, 1O2, O2- was the result of joint action of endogenous and exogenous ROS. Transcriptome analysis revealed that different RONS of cold plasma were responsible for Pseudomonas fluorescens inactivation and related to activation of intracellular antioxidant defense system and regulation of genes expression related to amino acid metabolism and energy metabolism, which promoting cellular process, catalytic activity and other biochemical pathways.

The Impact of Cr(III) and Cr(VI) on Lipid Accumulation in Chlorella pyrenoidosa

In this study, Chlorella pyrenoidosa was cultured with different concentrations of Cr(III) and Cr(VI), and the changes in biomass, lipid content, protein content and total sugar content of Chlorella pyrenoidosa under different culture conditions were detected. The effects of Cr(III) and Cr(VI) on the intracellular antioxidant system and related key enzymes of lipid synthesis were analyzed. The results showed that appropriate Cr(III) and Cr(VI) concentrations could make Chlorella pyrenoidosa regulate the contents of SOD, POD, ASA, CAT and GSH in cells, improve the enzyme activity of ACC and promote lipid synthesis. The aim was to investigate the mechanism of lipid synthesis by analyzing the distribution of Cr(III) and Cr(VI) in algal cells. The lipid content of Chlorella pyrenoidosa reached its highest level at 50.43 wt% and 38.00 wt% when both Cr(III) and Cr(VI) concentrations in the culture environment were 0.5 mg/L. These values were 1.37 and 1.03 times higher than the control group, respectively. The addition of appropriate Cr(III) and Cr(VI) concentrations can increase ME enzyme activity and decrease PEPC enzyme activity, shorten the biomass accumulation cycle and prolong the lipid synthesis cycle.

Precisely Self-Cooperative Nanoassembly Enables Photothermal/Ferroptosis Synergistic Tumor Eradication.

Ferroptosis is identified as a potential target for anticancer therapy. However, most conventional ferroptosis inducers not only fail to trigger intracellular lipid peroxidation storm, but are also prone to cause ferroptosis-related toxicity through off-target destruction of intracellular antioxidant defense systems. Therefore, a potent and highly tumor-specific ferroptosis induction modality is desired. Herein, a self-cooperative nanomedicine for imaging-guided photothermal ferrotherapy, which is fabricated based on molecular nanoassembly (NA) of DiR (a photothermal probe) and ferrocene (Fc, a reactant of the Fenton reaction), is elaborately exploited. DiR-elicited hyperthermia induces both photothermal therapy (PTT) and a significant acceleration of the kinetics of the Fc-involved Fenton reaction, collaboratively causing a lipid peroxidation storm in tumor cells. In turn, plenty of lipid peroxides boost PTT through the downregulation of heat shock protein 90. As expected, such a self-cooperative NA demonstrates synergetic tumor eradication in the 4T1 breast tumor-bearing mice xenograft model. This study offers a novel nanotherapeutic paradigm for precise multimodal cancer therapy.

Combined effect of cold plasma-activated oxygen (CPAO) and microwave on microbial decontamination and quality of milkshake powder

This study presents a new method combining cold plasma-activated oxygen (CPAO) and microwave (MW) to decontaminate milkshake powder, exploring its effectiveness, mechanisms, and quality impact. CPAO (6 min) alone reduced bacterial load by 0.419 log CFU/g, and MW (3 min) by 0.030 log CFU/g. However, their co-application significantly amplified decontamination, achieving a 1.265 log CFU/g reduction. CPAO-MW co-treatment inflicted more oxidative damage on bacterial cell membranes and intracellular antioxidant defense system, leading to higher mortality. It also raised protein and lipid oxidation, while decreasing vitamin C and A levels in the powder. Specifically, CPAO (6 min)-MW (3 min) co-treatment increased the carbonyl content from 0.438 to 0.891 nmol/mg protein, malondialdehyde from 0.824 to 0.996 mg/kg, and lowered vitamin C from 162.151 to 137.640 mg/kg, and vitamin A from 2.05 to 1.38 mg/kg. This study shows CPAO-MW is effective for decontaminating powdered foods but highlights a need to reduce negative effects.

Moderate-Intensity Swimming Alleviates Oxidative Injury in Ischemic Heart

The global burden of cardiovascular diseases is indisputable, as it claims nearly 18 million lives a year. In this current study, we aimed to prove that exercise, a cornerstone in cardiovascular disease management, emerges as a powerful tool in the pathology of myocardial ischemia. Male rats were divided into three groups: pre-swimming training + isoproterenol (ISO) treated, isoproterenol-treated, and control-sedentary. Myocardial infarction was induced by the subcutaneous injection of 1.0 mg/kg ISO. After the subsequent rest period, the animals swam for 3 weeks, every day for 25 min. At the end of the experiment, the serum levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), as well as the cardiac concentrations of reactive oxygen species (ROS), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were determined. Our results indicate that both cardiac injury biomarkers (ANP, BNP) and ROS levels were significantly lower in swimming rats compared to the sedentary animals. Moreover, the level of enzymatic components of the intracellular antioxidant system, CAT, SOD, and GPx were increased in swimming animals after ISO-induced myocardial infarction. Our findings support the fact that moderate-intensity swimming training can be efficiently used to prevent myocardial infarction-induced ischemic injury, by inhibiting ROS production and strengthening intracellular antioxidant defense.

The role of ferroptosis in colorectal cancer and its potential synergy with immunotherapy.

Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies worldwide. Recently, ferroptosis, a novel form of regulated cell death characterized by iron dependency and lipid peroxidation, has garnered significant attention from researchers. The mechanisms underlying ferroptosis, including intracellular iron levels, lipid peroxidation, and antioxidant system regulation, offer new insights into cancer treatment strategies. This study aims to explore the emerging role of ferroptosis in the context of immunotherapy for CRC, highlighting its potential mechanisms and clinical applications. We employed a comprehensive review of current literature to elucidate the biological mechanisms of ferroptosis, its relationship with CRC, and the interplay between ferroptosis and immunotherapy. Ferroptosis reshapes the tumor microenvironment (TME) by regulating intracellular iron levels, lipid metabolism, and antioxidant systems, significantly enhancing the efficacy of immune checkpoint inhibitors (ICIs). Meanwhile, traditional Chinese medicine therapies promote antitumor immunity by modulating the TME and inducing ferroptosis. Additionally, advances in nanotechnology have facilitated precise therapy by enabling targeted delivery of ferroptosis inducers or immunomodulators, transforming "cold" tumors into "hot" tumors and further boosting ICI efficacy. This study comprehensively reviews the latest developments in ferroptosis, immunotherapy, traditional Chinese medicine, and nanotechnology in CRC, highlighting the importance of ferroptosis-related biomarkers and novel inducers for personalized treatment. In summary, ferroptosis offers a promising strategy to overcome CRC therapy resistance and enhance immunotherapy efficacy, warranting further investigation and translational application.

A self-healing injectable hydrogel integrated with enzymatic and nonenzymatic antioxidants as artificial antioxidant defense system for diabetic wound healing

Chronic diabetic wounds seriously threaten human health due to their intractable nature in a complex pathological microenvironment that contains oxidative stress, persistent inflammatory status, hypoxia and bacterial infections, of which oxidative damage contributing the most. Applied materials that can mimic the natural intracellular antioxidant defense system are perceived to have huge therapeutic potential. Herein, we present a novel strategy to prepare a versatile nanocomposite hydrogel by incorporating the nanoenzyme (manganese dioxide (MnO2)) and nonenzymatic antioxidant components (polydopamine (PDA)) in a dynamic hydrogel network composed of thioctic acid and tannic acid (TA). The prepared hydrogel exhibited outstanding adhesive and injectable properties, making it adapt perfectly to wounds with different shapes and depths. More importantly, encapsulation of PDA@MnO2 nanoparticles (NPs) conferred the hydrogel with superior antioxidant performance to effectively scavenge multiple types of reactive nitrogen and oxygen species (RNOS) and reduce the inflammatory response by regulating macrophage polarization. Meanwhile, the hydrogel showed high-performance catalyzing ability to transfer hydrogen peroxide (H2O2) into oxygen (O2), which could further alleviate hypoxic wound environment. Moreover, the nanocomposite hydrogel exhibited excellent near-infrared (NIR) photothermal antibacterial effect. Collectively, our findings indicate that the synthesized nanocomposite hydrogel shows potential for use in a clinical setting to treat diabetic wounds.

Fast Antioxidation Kinetics of Glutathione Intracellularly Monitored by a Dual‐Wire Nanosensor

AbstractThe glutathione (GSH) system is one of the most powerful intracellular antioxidant systems for the elimination of reactive oxygen species (ROS) and maintaining cellular redox homeostasis. However, the rapid kinetics information (at the millisecond to the second level) during the dynamic antioxidation process of the GSH system remains unclear. As such, we specifically developed a novel dual‐wire nanosensor (DWNS) that can selectively and synchronously measure the levels of GSH and ROS with high temporal resolution, and applied it to monitor the transient ROS generation as well as the rapid antioxidation process of the GSH system in individual cancer cells. These measurements revealed that the glutathione peroxidase (GPx) in the GSH system is rapidly initiated against ROS burst in a sub‐second time scale, but the elimination process is short‐lived, ending after a few seconds, while some ROS are still present in the cells. This study is expected to open new perspectives for understanding the GSH antioxidant system and studying some redox imbalance‐related physiological.

Fast Antioxidation Kinetics of Glutathione Intracellularly Monitored by a Dual-Wire Nanosensor.

The glutathione (GSH) system is one of the most powerful intracellular antioxidant systems for the elimination of reactive oxygen species (ROS) and maintaining cellular redox homeostasis. However, the rapid kinetics information (at the millisecond to the second level) during the dynamic antioxidation process of the GSH system remains unclear. As such, we specifically developed a novel dual-wire nanosensor (DWNS) that can selectively and synchronously measure the levels of GSH and ROS with high temporal resolution, and applied it to monitor the transient ROS generation as well as the rapid antioxidation process of the GSH system in individual cancer cells. These measurements revealed that the glutathione peroxidase (GPx) in the GSH system is rapidly initiated against ROS burst in a sub-second time scale, but the elimination process is short-lived, ending after a few seconds, while some ROS are still present in the cells. This study is expected to open new perspectives for understanding the GSH antioxidant system and studying some redox imbalance-related physiological.