Regulation Of Reactive Oxygen Species Research Articles

DGK5β-derived phosphatidic acid regulates ROS production in plant immunity by stabilizing NADPH oxidase

In plant immunity, phosphatidic acid (PA) regulates reactive oxygen species (ROS) by binding to respiratory burst oxidase homolog D (RBOHD), an NADPH oxidase responsible for ROS production. Here, we analyze the influence of PA binding on RBOHD activity and the mechanism of RBOHD-bound PA generation. PA binding enhances RBOHD protein stability by inhibiting vacuolar degradation, thereby increasing chitin-induced ROS production. Mutations in diacylglycerol kinase 5 (DGK5), which phosphorylates diacylglycerol to produce PA, impair chitin-induced PA and ROS production. The DGK5 transcript DGK5β (but not DGK5α) complements reduced PA and ROS production in dgk5-1 mutants, as well as resistance to Botrytis cinerea. Phosphorylation of S506 residue in the C-terminal calmodulin-binding domain of DGK5β contributes to the activation of DGK5β to produce PA. These findings suggest that DGK5β-derived PA regulates ROS production by inhibiting RBOHD protein degradation, elucidating the role of PA-ROS interplay in immune response regulation.

NAT2 Gene Variants as a Provocative Factor for the Severe Course of COVID-19 Pneumonia in Ukrainian Patients

Background: Previous studies indicate a close relationship between the severity of COVID-19 and oxidative stress. N-acetyltransferase 2 (NAT2) is an enzyme that metabolizes a wide range of xenobiotics and plays an important role in the regulation of reactive oxygen species, consequently contributing to the development of oxidative stress. Aim: To determine the impact of NAT2 gene variants on the risk of developing and the progression of severe COVID-19-associated pneumonia in patients from the Poltava region of Ukraine. Methods: The study included 117 patients who were diagnosed with severe COVID-19 pneumonia and received treatment in the intensive care unit. The NAT2 gene variants were identified through the PCR-RFLP method. Results: The presence of the AA genotype of the A803G variant in patients with severe COVID-19 pneumonia is associated with an almost 3-fold reduction in the risk of lethal outcomes. The presence of the TT genotype of the C481T variant was associated with the need for artificial lung ventilation. Patients in the study group with a heterozygous GA genotype of the G590A variant demonstrated a notable rise in the risk of developing systemic inflammatory response syndrome and acute respiratory distress syndrome, with a nearly 2.5-fold and 3-fold increase, respectively. The G857A variant was not associated with the risk of developing the above-- mentioned complications in the examined patients. Conclusion: The obtained results suggested that the NAT2 gene variants might influence the incidence, course, and adverse consequences of COVID-19.

Oxidase enzyme genes are differentially expressed during Acanthamoeba castellanii encystment.

Acanthamoeba castellanii, a ubiquitous protozoan, is responsible for significant diseases such as Acanthamoeba keratitis and granulomatous amoebic encephalitis. A crucial survival strategy of A. castellanii involves the formation of highly resistant cysts during adverse conditions. This study delves into the cellular processes underpinning encystment, focusing on gene expression changes related to reactive oxygen species (ROS) balance, with a particular emphasis on mitochondrial processes. Our findings reveal a dynamic response within the mitochondria during encystment, with the downregulation of key enzymes involved in oxidative phosphorylation (COX, AOX, and NADHalt) during the initial 48h, followed by their overexpression at 72h. This orchestrated response likely creates a pro-oxidative environment, facilitating encystment. Analysis of other ROS processing enzymes across the cell reveals differential expression patterns. Notably, antioxidant enzymes, such as catalases, glutaredoxins, glutathione S-transferases, peroxiredoxins, and thioredoxins, mirror the mitochondrial trend of downregulation followed by upregulation. Additionally, glycolysis and gluconeogenesis are downregulated during the early stages in order to potentially balance the metabolic requirement of the cyst. Our study underscores the importance of ROS regulation in Acanthamoeba encystment. Understanding these mechanisms offers insights into infection control and identifies potential therapeutic targets. This work contributes to unraveling the complex biology of A. castellanii and may aid in combatting Acanthamoeba-related infections. Further research into ROS and oxidase enzymes is warranted, given the organism's remarkable respiratory versatility.

Signalling regulation of reactive oxygen species in fish inflammation

AbstractReactive oxygen species (ROS), which are key cellular signalling molecules, are reactive chemicals containing oxygen. Cell survival or death is a critical issue in the inflammatory response. Accumulation of ROS involves ROS generation and scavenging, which determine ROS homeostasis. Understanding the roles of ROS in modulating the inflammatory response in fish is vital for helping protect fish from the damage of water pollutants in harsh environmental conditions. ROS‐related key genes and signalling pathways are relatively conserved in fish but vary among different species. Recent frequent incidences of fish diseases have posed a considerable challenge to large‐scale aquaculture. ROS is important in stress perception, integration of diverse stress‐responsive signalling networks, and activation of animal defence mechanisms, which frequently occur during inflammation in fish. This review summarises recent studies on ROS signalling pathways during inflammation in fish. Furthermore, it examines the relationship between ROS and inflammation in fish. This review may contribute to the understanding of the underlying mechanisms by which ROS regulate inflammation in fish and provide suggestions for sustainable development in aquaculture.

Inhibition of palmitoyltransferase ZDHHC12 sensitizes ovarian cancer cells to cisplatin through ROS-mediated mechanisms.

Platinum-based therapies have revolutionized the treatment of high-grade serous ovarian cancer (HGSOC). However, high rates of disease recurrence and progression remain a major clinical concern. Impaired mitochondrial function and dysregulated reactive oxygen species (ROS), hallmarks of cancer, hold potential as therapeutic targets for selectively sensitizing cisplatin treatment. Here, we uncover an oncogenic role of the palmitoyltransferase ZDHHC12 in regulating mitochondrial function and ROS homeostasis in HGSOC cells. Analysis of The Cancer Genome Atlas (TCGA) ovarian cancer data revealed significantly elevated ZDHHC12 expression, demonstrating the strongest positive association with ROS pathways among all ZDHHC enzymes. Transcriptomic analysis of independent ovarian cancer datasets and the SNU119 cell model corroborated this association, highlighting a strong link between ZDHHC12 expression and signature pathways involving mitochondrial oxidative metabolism and ROS regulation. Knockdown of ZDHHC12 disrupted this association, leading to increased cellular complexity, ATP levels, mitochondrial activity, and both mitochondrial and cellular ROS. This dysregulation, achieved by the siRNA knockdown of ZDHHC12 or treatment with the general palmitoylation inhibitor 2BP or the fatty acid synthase inhibitor C75, significantly enhanced cisplatin cytotoxicity in 2D and 3D spheroid models of HGSOC through ROS-mediated mechanisms. Markedly, ZDHHC12 inhibition significantly augmented the anti-tumor activity of cisplatin in an ovarian cancer xenograft tumor model, as well as in an ascites-derived organoid line of platinum-resistant ovarian cancer. Our data suggest the potential of ZDHHC12 as a promising target to improve the outcome of HGSOCs in response to platinum-based chemotherapy.

Evolution of the Major Components of Innate Immunity in Animals.

Innate immunity is present in all animals. In this review, we explore the main conserved mechanisms of recognition and innate immune responses among animals. In this sense, we discuss the receptors, critical for binding to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs); the downstream signaling proteins; and transcription factors that govern immune responses. We also highlight conserved inflammatory mediators that are induced after the recognition of DAMPs and PAMPs. At last, we discuss the mechanisms that are involved in the regulation and/or generation of reactive oxygen species (ROS), influencing immune responses, like heme-oxygenases (HOs).

ROS: Executioner of regulating cell death in spinal cord injury.

The damage to the central nervous system and dysfunction of the body caused by spinal cord injury (SCI) are extremely severe. The pathological process of SCI is accompanied by inflammation and injury to nerve cells. Current evidence suggests that oxidative stress, resulting from an increase in the production of reactive oxygen species (ROS) and an imbalance in its clearance, plays a significant role in the secondary damage during SCI. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulatory molecule for cellular redox. This review summarizes recent advancements in the regulation of ROS-Nrf2 signaling and focuses on the interaction between ROS and the regulation of different modes of neuronal cell death after SCI, such as apoptosis, autophagy, pyroptosis, and ferroptosis. Furthermore, we highlight the pathways through which materials science, including exosomes, hydrogels, and nanomaterials, can alleviate SCI by modulating ROS production and clearance. This review provides valuable insights and directions for reducing neuronal cell death and alleviating SCI through the regulation of ROS and oxidative stress.

An apoptosis-inducing factor controls programmed cell death and laccase expression during fungal interactions

Apoptotic-like programmed cell death (PCD) is one of the main strategies for fungi to resist environmental stresses and maintain homeostasis. The apoptosis-inducing factor (AIF) has been shown in different fungi to trigger PCD through upregulating reactive oxygen species (ROS). This study identified a mitochondrial localized AIF homolog, CcAIF1, from Coprinopsis cinerea monokaryon Okayama 7. Heterologous overexpression of CcAIF1 in Saccharomyces cerevisiae caused apoptotic-like PCD of the yeast cells. Ccaif1 was increased in transcription when C. cinerea interacted with Gongronella sp. w5, accompanied by typical apoptotic-like PCD in C. cinerea, including phosphatidylserine externalization and DNA fragmentation. Decreased mycelial ROS levels were observed in Ccaif1 silenced C. cinerea transformants during cocultivation, as well as reduction of the apoptotic levels, mycelial growth, and asexual sporulation. By comparison, Ccaif1 overexpression led to the opposite phenotypes. Moreover, the transcription and expression levels of laccase Lcc9 decreased by Ccaif1 silencing but increased firmly in Ccaif1 overexpression C. cinerea transformants in coculture. Thus, in conjunction with our previous report that intracellular ROS act as signal molecules to stimulate defense responses, we conclude that CcAIF1 is a regulator of ROS to promote apoptotic-like PCD and laccase expression in fungal-fungal interactions. In an axenic culture of C. cinerea, CcAIF1 overexpression and H2O2 stimulation together increased laccase secretion with multiplied production yield. The expression of two other normally silent isozymes, Lcc8 and Lcc13, was unexpectedly triggered along with Lcc9.Key points• Mitochondrial CcAIF1 induces PCD during fungal-fungal interactions• CcAIF1 is a regulator of ROS to trigger the expression of Lcc9 for defense• CcAIF1 overexpression and H2O2 stimulation dramatically increase laccase production

OsUGE2 Regulates Plant Growth through Affecting ROS Homeostasis and Iron Level in Rice

BackgroundThe growth and development of rice (Oryza sativa L.) are affected by multiple factors, such as ROS homeostasis and utilization of iron. Here, we demonstrate that OsUGE2, a gene encoding a UDP-glucose 4-epimerase, controls growth and development by regulating reactive oxygen species (ROS) and iron (Fe) level in rice. Knockout of this gene resulted in impaired growth, such as dwarf phenotype, weakened root growth and pale yellow leaves. Biochemical analysis showed that loss of function of OsUGE2 significantly altered the proportion and content of UDP-Glucose (UDP-Glc) and UDP-Galactose (UDP-Gal). Cellular observation indicates that the impaired growth may result from decreased cell length. More importantly, RNA-sequencing analysis showed that knockout of OsUGE2 significantly influenced the expression of genes related to oxidoreductase process and iron ion homeostasis. Consistently, the content of ROS and Fe are significantly decreased in OsUGE2 knockout mutant. Furthermore, knockout mutants of OsUGE2 are insensitive to both Fe deficiency and hydrogen peroxide (H2O2) treatment, which further confirmed that OsUGE2 control rice growth possibly through Fe and H2O2 signal. Collectively, these results reveal a new pathway that OsUGE2 could affect growth and development via influencing ROS homeostasis and Fe level in rice.

Systems-level analyses dissociate genetic regulators of reactive oxygen species and energy production.

Respiratory chain dysfunction can decrease ATP and increase reactive oxygen species (ROS) levels. Despite the importance of these metabolic parameters to a wide range of cellular functions and disease, we lack an integrated understanding of how they are differentially regulated. To address this question, we adapted a CRISPRi- and FACS-based platform to compare the effects of respiratory gene knockdown on ROS to their effects on ATP. Focusing on genes whose knockdown is known to decrease mitochondria-derived ATP, we showed that knockdown of genes in specific respiratory chain complexes (I, III, and CoQ10 biosynthesis) increased ROS, whereas knockdown of other low ATP hits either had no impact (mitochondrial ribosomal proteins) or actually decreased ROS (complex IV). Moreover, although shifting metabolic conditions profoundly altered mitochondria-derived ATP levels, it had little impact on mitochondrial or cytosolic ROS. In addition, knockdown of a subset of complex I subunits-including NDUFA8, NDUFB4, and NDUFS8-decreased complex I activity, mitochondria-derived ATP, and supercomplex level, but knockdown of these genes had differential effects on ROS. Conversely, we found an essential role for ether lipids in the dynamic regulation of mitochondrial ROS levels independent of ATP. Thus, our results identify specific metabolic regulators of cellular ATP and ROS balance that may help dissect the roles of these processes in disease and identify therapeutic strategies to independently target energy failure and oxidative stress.

Retracted: Hypoxia-Activated PI3K/Akt Inhibits Oxidative Stress via the Regulation of Reactive Oxygen Species in Human Dental Pulp Cells.

[This retracts the article DOI: 10.1155/2019/6595189.].

Enhancing bovine immune, antioxidant and anti-inflammatory responses with vitamins, rumen-protected amino acids, and trace minerals to prevent periparturient mastitis.

Mastitis, the inflammatory condition of mammary glands, has been closely associated with immune suppression and imbalances between antioxidants and free radicals in cattle. During the periparturient period, dairy cows experience negative energy balance (NEB) due to metabolic stress, leading to elevated oxidative stress and compromised immunity. The resulting abnormal regulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with increased non-esterified fatty acids (NEFA) and β-hydroxybutyric acid (BHBA) are the key factors associated with suppressed immunity thereby increases susceptibility of dairy cattle to infections, including mastitis. Metabolic diseases such as ketosis and hypocalcemia indirectly contribute to mastitis vulnerability, exacerbated by compromised immune function and exposure to physical injuries. Oxidative stress, arising from disrupted balance between ROS generation and antioxidant availability during pregnancy and calving, further contributes to mastitis susceptibility. Metabolic stress, marked by excessive lipid mobilization, exacerbates immune depression and oxidative stress. These factors collectively compromise animal health, productive efficiency, and udder health during periparturient phases. Numerous studies have investigated nutrition-based strategies to counter these challenges. Specifically, amino acids, trace minerals, and vitamins have emerged as crucial contributors to udder health. This review comprehensively examines their roles in promoting udder health during the periparturient phase. Trace minerals like copper, selenium, and calcium, as well as vitamins; have demonstrated significant impacts on immune regulation and antioxidant defense. Vitamin B12 and vitamin E have shown promise in improving metabolic function and reducing oxidative stress followed by enhanced immunity. Additionally, amino acids play a pivotal role in maintaining cellular oxidative balance through their involvement in vital biosynthesis pathways. In conclusion, addressing periparturient mastitis requires a holistic understanding of the interplay between metabolic stress, immune regulation, and oxidative balance. The supplementation of essential amino acids, trace minerals, and vitamins emerges as a promising avenue to enhance udder health and overall productivity during this critical phase. This comprehensive review underscores the potential of nutritional interventions in mitigating periparturient bovine mastitis and lays the foundation for future research in this domain.

Achieving precise non-invasive ROS spatiotemporal manipulation for colon cancer immunotherapy

Colon cancer (CC) stands as a formidable global health challenge, ranking as the third leading cause of cancer-related mortality. Traditional photodynamic therapy encounters limitations stemming from the limited penetration depth of light and the effective regulation of reactive oxygen species (ROS). Here, we present an in-situ ROS spatiotemporal manipulation system that synergizes the power of piezoelectric nanoparticles with potent immune adjuvants. This exclusive ROS nanogenerator exhibits precision in targeting colon tumor sites, inducing controlled oxidative stress to eliminate malignant cells, while simultaneously unleashing the full potential of the immune system to suppress cancer cell growth and impede metastasis. Notably, this system achieves spatiotemporal manipulation of ROS through piezocatalytic mechanisms triggered self-generated ROS. Moreover, it skillfully customizes ROS production in response to tumor size, optimizing therapeutic efficacy with precision. To enhance the therapeutic efficacy, glucan, a bioactive polysaccharide that augments the immune response while simultaneously inhibiting the spread of cancer cells, is integrated. This cancer treatment approach is enabling precise ROS generation and immune modulation at the tumor site, ushering in a new era of dynamic immunotherapy.

Tea Polyphenols Inhibit the Occurrence of Enzymatic Browning in Fresh-Cut Potatoes by Regulating Phenylpropanoid and ROS Metabolism.

During fresh-cut processing, potatoes lose their inherent protective cellular structure, leading to enzymatic browning that compromises sensory and edible quality. Tea polyphenols (TPs), natural preservatives with potent reducing properties, are hypothesized to impact this browning process. However, their influence and regulatory mechanism on the enzymatic browning of fresh-cut potatoes remain poorly understood. This study used the "Holland Seven" potato as the research material to explore the effects of a treatment with different TP concentrations (0.1 g L-1, 0.2 g L-1, and 0.3 g L-1) on the browning phenomenon and quality of fresh-cut potatoes during storage. The results showed that appropriate concentrations of TP treatment had a good preservation effect on the appearance and edible quality of fresh-cut potatoes. Furthermore, exogenous TP treatment reduced the content of enzymatic browning substrates (caffeic acid, p-coumaric acid, and ferulic acid) by regulating phenylpropanoid metabolism. Meanwhile, TP treatment augmented the activities of antioxidative enzymes (superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase), maintained higher levels of ascorbic acid (Vc), and reduced glutathione (GSH). Consequently, the TP treatment could inhibit enzymatic browning by regulating reactive oxygen species (ROS) metabolism and the Vc-GSH cycle in fresh-cut potatoes.

Construction of a novel pyrene-based two-dimensional supramolecular organic framework and the selective regulation of reactive oxygen species for photocatalysis

We report herein a novel pyrene-based two-dimensional supramolecular organic framework (SOF) in water via host–guest interactions, which exhibits regulation of ROS and high photocatalytic efficiency.

Natural Flavonoid-Derived Enzyme Mimics DHKNase Balance the Two-Edged Reactive Oxygen Species Function for Wound Healing and Inflammatory Bowel Disease Therapy.

Rational regulation of reactive oxygen species (ROS) plays a vital importance in maintaining homeostasis of living biological systems. For ROS-related pathologies, chemotherapy technology derived from metal nanomaterials currently occupies a pivotal position. However, they suffer from inherent issues such as complicated synthesis, batch-to-batch variability, high cost, and potential biological toxicity caused by metal elements. Here, we reported for the first time that dual-action 3,5-dihydroxy-1-ketonaphthalene-structured small-molecule enzyme imitator (DHKNase) exhibited 2-edged ROS regulation, catering to the execution of physiology-beneficial ROS destiny among diverse pathologies in living systems. Based on this, DHKNase is validated to enable remarkable therapeutic effects in 2 classic disease models, including the pathogen-infected wound-healing model and the dextran sulfate sodium (DSS)-caused inflammatory bowel disease (IBD). This work provides a guiding landmark for developing novel natural small-molecule enzyme imitator and significantly expands their application potential in the biomedical field.

The role of SIRT3 in homeostasis and cellular health.

Mitochondria are responsible for maintaining cellular energy levels, and play a major role in regulating homeostasis, which ensures physiological function from the molecular to whole animal. Sirtuin 3 (SIRT3) is the major protein deacetylase of mitochondria. SIRT3 serves as a nutrient sensor; under conditions of mild metabolic stress, SIRT3 activity is increased. Within the mitochondria, SIRT3 regulates every complex of the electron transport chain, the tricarboxylic acid (TCA) and urea cycles, as well as the mitochondria membrane potential, and other free radical scavengers. This article reviews the role of SIRT3 in regulating homeostasis, and thus physiological function. We discuss the role of SIRT3 in regulating reactive oxygen species (ROS), ATP, immunological function and mitochondria dynamics.

Transcriptomic Analysis of Gene Expression and Effect of Electromagnetic Field in Brain Tissue after Traumatic Brain Injury.

Traumatic brain injury (TBI) due to a direct blow or penetrating injury to the head damages the brain tissue and affects brain function. Primary and secondary damage to the brain tissue increases disability, morbidity, and mortality and costs millions of dollars in treatment. Injury to the brain tissue results in the activation of various inflammatory and repair pathways involving many cellular and molecular factors. Increased infiltration of immune cells to clear the debris and lesion healing, activation of Schwann cells, myelination, oligodendrocyte formation, and axonal regeneration occur after TBI to regenerate the tissue. However, secondary damage to brain tissue results in behavioral symptoms. Repair and regeneration are regulated by a complex cascade involving various cells, hormones, and proteins. A change in the expression of various proteins due to altered gene expression may be the cause of impaired repair and the sequelae in TBI. In this pilot study, we used a Yucatan miniswine model of TBI with and without electromagnetic field (EMF) stimulation and investigated the differential gene expression between injured and non-injured cortex tissues. We found several differentially expressed genes including INSC, TTR, CFAP126, SEMA3F, CALB1, CDH19, and SERPINE1. These genes are associated with immune cell infiltration, myelination, reactive oxygen species regulation, thyroid hormone transportation, cell proliferation, and cell migration. There was a time-dependent effect of EMF stimulation on the gene and protein expression. The findings support the beneficial effect of EMF stimulation in the repair process following TBI.

Protective Effect of Berberine on Acute Gastric Ulcer by Promotion of Tricarboxylic Acid Cycle-Mediated Arachidonic Acid Metabolism.

Peptic ulcer is a high incidence gastrointestinal disease in China. Berberine (BBR) is a natural product isolated from the Chinese herb Coptis chinensis Franch that has protective effects in digestive diseases. We aimed to evaluate the ability of BBR to attenuate acute gastric ulcer induced by one-time administration of ethanol in the rat. Tissue pathological morphology, macroscopic score, ulcer healing rate, and serum levels of the inflammatory cytokines nitric oxide (NO), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), and anti-inflammatory interleukin-10 (IL-10) were used to determine the efficacy of BBR and evaluated to identify the optimal dosage. Subsequently, transcriptome and metabolome sequencing were conducted in Control, Model, and optimal dosage groups to explore the pathogenesis of the disease and the mechanism of action of the drug. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), as well as those of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined by enzyme-linked immunosorbent assay to verify the results of transcriptomics and metabolomics analyses. BBR significantly improved the pathological morphology of gastric ulcers, increased the macroscopic score and healing rate, decreased serum levels of NO, IL-6, and PGE2, and increased serum levels of IL-10, thus effectively alleviating gastric ulcer severity. Transcriptome results showed that the therapeutic effect of BBR was mainly mediated by the arachidonic acid metabolism pathway at the gene level, which is closely associated with inflammation and increased levels of reactive oxygen species (ROS). The differentially accumulated metabolite prostaglandin E1, which is a negative regulator of ROS, was significantly up-regulated after BBR administration. The validation results indicated that BBR pretreatment increased SOD and GSH-Px enzyme activities, while reducing levels of the oxidative products MDA and MPO. This study demonstrated that BBR exerts a protective effect on acute gastric ulcer by promoting tricarboxylic acid cycle-mediated arachidonic acid metabolism.

PH-Responsive Wound Dressing Based on Biodegradable CuP Nanozymes for Treating Infected and Diabetic Wounds.

Nanozymes, emerging nanomaterials for wound healing, exhibit enzyme-like activity to modulate the levels of reactive oxygen species (ROS) at wound sites. Yet, the solo regulation of endogenous ROS by nanozymes often falls short, particularly in chronic refractory wounds with complex and variable pathological microenvironments. In this study, we report the development of a multifunctional wound dressing integrating a conventional alginate (Alg) hydrogel with a newly developed biodegradable copper hydrogen phosphate (CuP) nanozyme, which possesses good near-infrared (NIR) photothermal conversion capabilities, sustained Cu ion release ability, and pH-responsive peroxidase/catalase-mimetic catalytic activity. When examining acute infected wounds characterized by a low pH environment, the engineered Alg/CuP composite hydrogels demonstrated high bacterial eradication efficacy against both planktonic bacteria and biofilms, attributed to the combined action of catalytically generated hydroxyl radicals and the sustained release of Cu ions. In contrast, when applied to chronic diabetic wounds, which typically have a high pH environment, these composite hydrogels exhibit significant angiogenic performance. This is driven by the provision of catalytically generated dissolved oxygen and a beneficial supplement of Cu ions released from the degradable CuP nanozyme. Further, a mild thermal effect induced by NIR irradiation amplifies the catalytic activities and bioactivity of Cu ions, thereby enhancing the healing process of both infected and diabetic wounds. Our study validates that the synergistic integration of photothermal effects, catalytic activity, and released Cu ions can concurrently yield high antibacterial efficiency and tissue regenerative activity, rendering it highly promising for various clinical applications in wound healing.