Elimination Of Reactive Oxygen Species Research Articles

Multienzyme Mimicking Cascade Mn3O4 Catalyst to Augment Reactive Oxygen Species Elimination and Colorimetric Detection: A Study of Phase Variation upon Calcination Temperature.

Over decades, nanozyme has served as a better replacement of bioenzymes and fulfills most of the shortcomings and intrinsic disadvantages of bioenzymes. Recently, manganese-based nanomaterials have been highly noticed for redox-modulated multienzyme mimicking activity and wide applications in biosensing and biomedical science. The redox-modulated multienzyme mimicking activity was highly in tune with their size, surface functionalization, and charge on the surface and phases. On the subject of calcination temperature to Mn3O4 nanoparticles (NPs), its phase has been transformed to Mn2O3 NPs and Mn5O8 NPs upon different calcination temperatures. Assigning precise structure-property connections is made easier by preparing the various manganese oxides in a single step. The present study has focused on the variation of multienzyme mimicking activity with different phases of Mn3O4 NPs, so that they can be equipped for multifunctional activity with greater potential. Herein, spherical Mn3O4 NPs have been synthesized via a one-step coprecipitation method, and other phases are obtained by direct calcination. The calcination temperature varies to 100, 200, 400, and 600 °C and the corresponding manganese oxide NPs are named M-100, M-200, M-400, and M-600, respectively. The phase transformation and crystalline structure are evaluated by powder X-ray diffraction and selected-area electron diffraction analysis. The different surface morphologies are easily navigated by Fourier transform infrared, field-emission scanning electron microscopy, and high-resolution transmission electron microscopy analysis. Fortunately, for the mixed valence state of Mn3O4 NPs, all phases of manganese oxide NPs showed multienzyme mimicking activity including superoxide dismutase (SOD), catalase, oxidase (OD), and peroxidase; therefore, it offers a synergistic antioxidant ability to overexpose reactive oxygen species. Mn3O4 NPs exhibited good SOD-like enzyme activity, which allowed it to effectively remove the active oxygen (O2•-) from cigarette smoke. A sensitive colorimetric sensor with a low detection limit and a promising linear range has been designed to detect two isomeric phenolic pollutants, hydroquinone (H2Q) and catechol (CA), by utilizing optimized OD activity. The current probe has outstanding sensitivity and selectivity as well as the ability to visually detect two isomers with the unaided eye.

Reactive Oxygen Species and Mitochondrial Calcium's Roles in the Development of Atherosclerosis.

In the last decade, there has been increasing evidence connecting mitochondrial dysfunction to the onset and advancement of atherosclerosis. Both reactive oxygen species (ROS) and the disruption of mitochondrial calcium (Ca2+) regulation have garnered significant attention due to their involvement in various stages of atherosclerosis. This abstract discusses the potential therapeutic applications of targeting mitochondrial calcium (Ca2+) and reactive oxygen species (ROS), while also providing an overview of their respective roles in atherosclerosis. The abstract underscores the importance of mitochondrial Ca2+ homeostasis in cellular physiology, including functions such as energy production, cell death signaling, and maintaining redox balance. Alterations in the mitochondria's Ca2+ handling disrupt all these procedures and speed up the development of atherosclerosis. Reactive oxygen species (ROS), generated during mitochondrial respiration, are widely recognized as significant contributors to the development of atherosclerosis. Through modulating the function of calcium ion (Ca2+) transport proteins, ROS can impact the regulation of mitochondrial Ca2+ handling. These oxidative modifications lead to vascular remodeling and plaque formation by impairing endothelial function, encouraging the recruitment of inflammatory cells, and promoting smooth muscle cell proliferation. Preclinical investigations indicate that interventions aimed at regulating the production and elimination of reactive oxygen species (ROS) hold promise for mitigating atherosclerosis. Targeting mitochondrial processes represents a prospective therapeutic strategy for addressing this condition. Further research is necessary to elucidate the intricate molecular mechanisms associated with mitochondrial dysfunction in atherosclerosis and develop effective therapeutic strategies to decelerate disease progression.

Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.

Sources of fertilizers on the phytotechnical characteristics, oxidative stress and thymol production of Thymus vulgaris L.

The objective of this study was to assess the effects of different fertilizer sources on the phytotechnical characteristics, oxidative stress, and thymol production of Thymus vulgaris. The experiment was conducted in 3-dm³ pots containing soil:sand (2:1) + treatment (no fertilizer, organic fertilizer, or chemical fertilizer). The organic fertilizer was 8 kg m-2 of an equal mixture of bovine, goat, and quail manures. The variables assessed were leaf, stem, root, and total dry weights; chlorophyll and carotenoid contents; leaf nutrients; total polyphenols; total antioxidant capacity; oxygen radical absorption capacity; DPPH free radical scavenging activity; essential oil content; and thymol production, content, and yield. Organic fertilization significantly increased the variables assessed and reduced oxidative stress indicators. It resulted in gains in the dry weight of the plants and the accumulation of nutrients in dry leaves of T. vulgaris. For the quantitative parameters of the essential oil and thymol, organic fertilization was significantly higher than the other treatments, especially for thymol content and yield. T. vulgaris plants fertilized with organic fertilizer maximize their plant production and their yield of compounds of interest, such as thymol, possibly because these outputs indicate a balance between improved vegetative production and the elimination of reactive oxygen species.

Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing

Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal–organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors. Natural superoxide dismutase (SOD) and an artificial enzyme were spatially organized in these hierarchical mesoMOFs, forming a cascade antioxidant defense system, and presenting efficient intracellular and extracellular ROS scavenging performance. In vivo experiments demonstrated that the SOD@HMUiO-MnTCPP nanoparticles (S@M@H NPs) significantly accelerated diabetic wound healing. Transcriptomic and western blot results further indicated that the nanocomposite could inhibit fibroblast senescence and ferroptosis as well as the stimulator of interferon genes (STING) signaling pathway activation in macrophages mediated by mitochondrial oxidative stress through ROS elimination. Thus, the biomimetic multi-enzyme cascade catalytic system with spatial ordering demonstrated a high potential for diabetic wound healing, where senescence, ferroptosis, and STING signaling pathways may be potential targets.Graphical Schematic diagram showing the proposed mechanism that S@M@H NPs promoted diabetic wound healing

An Injectable Black Phosphorus Hydrogel for Rapid Tooth Extraction Socket Healing.

The excess production of reactive oxygen species (ROS) will delay tooth extraction socket (TES) healing. In this study, we developed an injectable thermosensitive hydrogel (NBP@BP@CS) used to treat TES healing. The hydrogel formulation incorporated black phosphorus (BP) nanoflakes, recognized for their accelerated alveolar bone regeneration and ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator aimed at enhancing angiogenesis. In vivo investigations strongly demonstrated that NBP@BP@CS improved TES healing due to antioxidation and promotion of alveolar bone regeneration by BP nanoflakes. The sustained release of NBP from the hydrogel promoted neovascularization and vascular remodeling. Our results demonstrated that the designed thermosensitive hydrogel provided great opportunity not only for ROS elimination but also for the promotion of osteogenesis and angiogenesis, reflecting the "three birds with one stone" concept, and has tremendous potential for rapid TES healing.

Role of Endothelial Nrf2 in the Regulation of Vasomotor Capacity and Arterial Blood Pressure

Introduction: Hypertension is a serious global public health issue. It is a complex disease with multiple factors contributing to its pathophysiology. One of these factors is oxidative stress, which results from an imbalance between the production and elimination of reactive oxygen species (ROS). Studies have shown that an increased ROS in endothelial cells (EC) impairs the vasodilatory capacity of blood vessels that contributes to blood pressure elevation. However, the modulation of endothelial ROS in the setting of hypertension is still not completely understood. To maintain cellular homeostasis, antioxidant enzymes continually adjust ROS levels under the orchestrating of transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of endogenous antioxidant responses. Modulation of endothelial Nrf2 expression may be a potential therapeutic option in hypertension. Therefore, the major objective of this study was to evaluate the role of Nrf2 in the modulation of endothelium associated vascular function and how it regulates vascular tone and blood pressure (BP). Methods: BP was measured in the conscious state using radiotelemetry transducers implanted into EC-specific Nrf2-knockout mice (Tie2-Cre-Nrf2 Floxed), EC specific Keap1 knockout mice (Tie2-Cre-Keap1 Floxed) and Wildtype (WT), all on the C57B6J background. After baseline BP recordings, mice were implanted with subcutaneous osmotic minipumps (7 days) for Angiotensin II (Ang II) (600ng/Kg/min) infusion or in a separate group L-nitroarginine methyl ester (L-NAME) (100 mg/kg/d in drinking water) for 2 weeks. For each intervention, recordings were done daily for 2 hours and one 24-hour measurement was done once per week. Endothelial specific downregulation or upregulation of Nrf2 was confirmed by immunohistochemistry on mouse aortic tissue and protein expression from mouse EC. For in-vitro studies: femoral-to-popliteal artery segments were harvested from mice of each genotype. Vasodilation was assessed in response to flow (30 uL·min−1) and acetylcholine (ACh, 10−7-10−3 M) with and without L-NAME, using video microscopy. Results: Ang II infusion significantly increased the mean arterial pressure (MAP) in each group when compared to their baseline values (Baseline: Nrf2KO = 92.6 ± 3.1, Keap1KO = 93.8 ± 4.1 and WT = 92.8 ± 1.7 mmHg; after Ang II Nrf2KO = 141.7 ± 3.8, Keap1KO = 121.9±5.4 and WT = 120.4±5.4 mmHg). The response to ANG II was significantly (p<0.05) augmented in Nrf2KO mice and stayed elevated for a longer period after emptying of the pump. The response to L-NAME was similar in both Nrf2KO and WT mice. Protein expression of Nrf2 was decreased in Nrf2KO mice in comparison to WT mice. Nrf2KO mice exhibited reduced endothelium-dependent vasodilation induced by flow (WT: 35.8± 1.3%, Nrf2KO: 24.1 ±1.7%; p<0.0001) and ACh (10−3M) (WT: 60.4±4.1%, Nrf2KO: 44.7± 2.1%; p<0.0001) compared to WT. In contrast, endothelial dependent vasodilatory responses to flow and Ach were markedly elevated in Keap1KO mice (51.3± 6.8%, p<0.0001; 71.6±11.6%, p<0.0087, respectively) compared to both WT and Nrf2KO mice. Conclusion: These results suggest that antioxidant defense mediated by Nrf2 in the endothelium plays a significant role in the modulation of blood pressure and vascular tone. Based on the L-NAME data, these effects are most likely due to an increase in the nitric oxide bioavailability and reduced ROS. University of Nebraska Theodore Hubbard foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Epigallocatechin-3-gallate derived polymer coated Prussian blue for synergistic ROS elimination and antibacterial therapy

Reactive oxygen species (ROS) play a vital role in wound healing process by fighting against invaded bacteria. However, excess ROS at the wound sites lead to oxidative stress that can trigger deleterious effects, causing cell death, tissue damage and chronic inflammation. Therefore, we fabricated a core–shell structured nanomedicine with antibacterial and antioxidant properties via a facile and green strategy. Specifically, Prussian blue (PB) nanozyme was fabricated and followed by coating a layer of epigallocatechin-3-gallate (EGCG)-derived polymer via polyphenolic condensation reaction and self-assembly process, resulting in PB@EGCG. The introduction of PB core endowed EGCG-based polyphenol nanoparticles with excellent NIR-triggered photothermal properties. Besides, owing to multiple enzyme-mimic activity of PB and potent antioxidant capacity of EGCG-derived polymer, PB@EGCG exhibited a remarkable ROS-scavenging ability, mitigated intracellular ROS level and protected cells from oxidative damage. Under NIR irradiation (808 nm, 1.5 W/cm2), PB@EGCG (50 µg/mL) exerted synergistic EGCG-derived polymer-photothermal antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus).In vivo therapeutic effect was evaluated using a S. aureus-infected rat model indicated PB@EGCG with a prominent bactericidal ability could modulate the inflammatory microenvironment and accelerate wound healing. Overall, this dual-functional nanomedicine provides a promising strategy for efficient antibacterial therapy.

Immunomodulatory melanin@Pt nanoparticle-reinforced adhesive hydrogels for healing diabetic oral ulcers

Oral ulcers may be addressed with various biomaterials infused with medications or cytokines. However, many patients derive little advantage from these substances due to inadequate adhesion, brief retention in the mouth, and diminished drug effectiveness. Here, we introduce a hydrogel patch (MPG3) consisting of a biopolymer matrix with light-activated adhesion features infused with platinum-decorated melanin nanoparticles that possess healing-promoting abilities. Initially, through straightforward local application, an adhesive hydrogel barrier forms over mucosal imperfections upon exposure to ultraviolet light. Following this, MPG3 exhibits outstanding oxygen production and reactive oxygen species elimination properties. These capabilities contribute to regulating the wound microenvironment, thereby expediting the wound's transition from the inflammatory to the proliferative stage. In rat models of oral ulcers, the MPG3 patch hastens recovery by modulating the inflammatory milieu of the damaged tissue and fostering expedited re-epithelialization and blood vessel formation. Conclusively, this light-activated adhesive hydrogel shows promise for swift wound healing and could revolutionize therapeutic approaches for treating clinical oral ulcers, especially in diabetic patients.

Silk fibroin hydrogel adhesive enables sealed-tight reconstruction of meniscus tears

Despite orientationally variant tears of the meniscus, suture repair is the current clinical gold treatment. However, inaccessible tears in company with re-tears susceptibility remain unresolved. To extend meniscal repair tools from the perspective of adhesion and regeneration, we design a dual functional biologic-released bioadhesive (S-PIL10) comprised of methacrylated silk fibroin crosslinked with phenylboronic acid-ionic liquid loading with growth factor TGF-β1, which integrates chemo-mechanical restoration with inner meniscal regeneration. Supramolecular interactions of β-sheets and hydrogen bonds richened by phenylboronic acid-ionic liquid (PIL) result in enhanced wet adhesion, swelling resistance, and anti-fatigue capabilities, compared to neat silk fibroin gel. Besides, elimination of reactive oxygen species (ROS) by S-PIL10 further fortifies localized meniscus tear repair by affecting inflammatory microenvironment with dynamic borate ester bonds, and S-PIL10 continuously releases TGF-β1 for cell recruitment and bridging of defect edge. In vivo rabbit models functionally evidence the seamless and dense reconstruction of torn meniscus, verifying that the concept of meniscus adhesive is feasible and providing a promising revolutionary strategy for preclinical research to repair meniscus tears.

Biodegradable Lipid-Modified Poly(Guanidine Thioctic Acid)s: A Fortifier of Lipid Nanoparticles to Promote the Efficacy and Safety of mRNA Cancer Vaccines.

Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.

Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic diseases, neurological disorders (Alzheimer's and Parkinson's diseases), and other disorders. To counteract the harmful effects of ROS, organisms have evolved a complex, three-line antioxidant defense system. The first-line defense mechanism is the most efficient and involves antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). This line of defense plays an irreplaceable role in the dismutation of superoxide radicals (O2•-) and hydrogen peroxide (H2O2). The removal of superoxide radicals by SOD prevents the formation of the much more damaging peroxynitrite ONOO- (O2•- + NO• → ONOO-) and maintains the physiologically relevant level of nitric oxide (NO•), an important molecule in neurotransmission, inflammation, and vasodilation. The second-line antioxidant defense pathway involves exogenous diet-derived small-molecule antioxidants. The third-line antioxidant defense is ensured by the repair or removal of oxidized proteins and other biomolecules by a variety of enzyme systems. This review briefly discusses the endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) and exogenous (e.g., smoking, radiation, drugs, pollution) sources of ROS (superoxide radical, hydrogen peroxide, hydroxyl radical, peroxyl radical, hypochlorous acid, peroxynitrite). Attention has been given to the first-line antioxidant defense system provided by SOD, CAT, and GPx. The chemical and molecular mechanisms of antioxidant enzymes, enzyme-related diseases (cancer, cardiovascular, lung, metabolic, and neurological diseases), and the role of enzymes (e.g., GPx4) in cellular processes such as ferroptosis are discussed. Potential therapeutic applications of enzyme mimics and recent progress in metal-based (copper, iron, cobalt, molybdenum, cerium) and nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) are also discussed. Moreover, attention has been given to the mechanisms of action of low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids(e.g., β-carotene, lycopene, lutein), flavonoids(e.g.,quercetin, anthocyanins, epicatechin), and glutathione (GSH)), the activation of transcription factors such as Nrf2, and the protection against chronic diseases. Given that there is a discrepancy between preclinical and clinical studies, approaches that may result in greater pharmacological and clinical success of low-molecular-weight antioxidant therapies are also subject to discussion.

Superoxide dismutase mimetic nanozymes attenuate cardiac microvascular ischemia–reperfusion injury associated with hyperhomocysteinemia

The combination of homocysteine (Hcy) and copper ion (Cu2+) induces cardiac microvascular ischemia–reperfusion injury (IRI) by causing oxidative stress in the reperfusion treatment of ischemic cardiopathy. Therefore, antioxidant elimination of reactive oxygen species (ROS) shows great potential in the treatment of IRI. Herein, cerium vanadate nanorods (CVNRs) were designed and developed as an efficient ROS scavenger for the treatment of myocardial IRI in hyperhomocysteinemic rat (HHcyR) model. Thanks to its outstanding superoxide dismutase (SOD)-like activity, the CVNRs showed a significant antioxidant effect in human cardiac microvascular endothelial cells treated with Hcy and Cu2+ under hypoxia/reperfusion condition and greatly preserved the morphology and function of mitochondria. Further intravenous administration of CVNRs significantly maintained the integrity and perfusion of microvasculature, minimized the microcirculation malfunction, and finally reduced the myocardial infarction and maintained the heart function after IRI. Moreover, the administration of CVNRs in HHcyR exhibited negligible organ toxicity and inflammation response, indicating their excellent biocompatibility and biosafety. Collectively, the SOD-mimicking CVNRs can serve as a promising antioxidant nanozyme to treat cardiac microvascular IRI complicated with hyperhomocysteinemia, providing a new prospect for the development of antioxidant nanozyme in IRI treatment even with other risk factors.

Promoting collateral formation in type 2 diabetes mellitus using ultra-small nanodots with autophagy activation and ROS scavenging

BackgroundImpaired collateral formation is a major factor contributing to poor prognosis in type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease. However, the current pharmacological treatments for improving collateral formation remain unsatisfactory. The induction of endothelial autophagy and the elimination of reactive oxygen species (ROS) represent potential therapeutic targets for enhancing endothelial angiogenesis and facilitating collateral formation. This study investigates the potential of molybdenum disulfide nanodots (MoS2 NDs) for enhancing collateral formation and improving prognosis.ResultsOur study shows that MoS2 NDs significantly enhance collateral formation in ischemic tissues of diabetic mice, improving effective blood resupply. Additionally, MoS2 NDs boost the proliferation, migration, and tube formation of endothelial cells under high glucose/hypoxia conditions in vitro. Mechanistically, the beneficial effects of MoS2 NDs on collateral formation not only depend on their known scavenging properties of ROS (H2O2, •O2-, and •OH) but also primarily involve a molecular pathway, cAMP/PKA-NR4A2, which promotes autophagy and contributes to mitigating damage in diabetic endothelial cells.ConclusionsOverall, this study investigated the specific mechanism by which MoS2 NDs mediated autophagy activation and highlighted the synergy between autophagy activation and antioxidation, thus suggesting that an economic and biocompatible nano-agent with dual therapeutic functions is highly preferable for promoting collateral formation in a diabetic context, thus, highlighting their therapeutic potential.Graphical

Photoactivated 9-methylacridine destroys midgut tissues of Aedes aegypti larvae by targeting ROS-mediated apoptosis in the mitochondrial pathway of midgut cells

An aromatic ring-containing compound with a wide range of biological activities, 9-methylacridine (AD-9-Me) is a precursor for the synthesis of various drugs. However, its photoactivation properties and mechanism of damage as a photo activator against Aedes aegypti are unknown. The toxic effects of AD-9-Me on Aedes aegypti mosquitoes were determined under light and non-light conditions. The results showed that the toxicity of AD-9-Me to mosquito larvae was significantly higher than that of the dark treatment after 24 h of light exposure; AD-9-Me was mainly distributed in the midgut of larvae, after 24 h of treatment, it can cause an increase in calcium ion concentration, reactive oxygen species (ROS) eruption and ROS accumulation by blocking the ROS elimination pathway in midgut cells. This in turn caused an increase in protein carbonyl and malondialdehyde (MDA) content, a decrease in mitochondrial membrane potential (MMP), a disruption of the barrier function of midgut tissues, a significant decrease in midgut weight and chitin content, which induced the up-regulation of AeDronc, AeCaspase8 and AeCaspase7 genes, leading to apoptotic cell death. In this study, we confirmed that AD-9-Me has photoactivation activity and mainly acts on the midgut of mosquito larvae, which can generate a large amount of ROS in the cells of the midgut and induce apoptosis to occur, resulting in the disruption of the function of the tissues of mosquito larvae, accelerating the death and delaying the development of the mosquito larvae.

Selenium nanoparticles/carboxymethyl chitosan/alginate antioxidant hydrogel for treating steroid-induced osteonecrosis of the femoral head

Oxidative stress plays a crucial role in steroid-induced osteonecrosis of the femoral head (SONFH). Although several antioxidant strategies have been investigated for treating SONFH, their antioxidant efficiencies and therapeutic effects remain unsatisfactory. Here, we developed a selenium nanoparticles/carboxymethyl chitosan/alginate (SeNPs/CMC/Alg) antioxidant hydrogel and evaluated its ability to treat SONFH. In vitro assays indicated that the SeNPs/CMC/Alg hydrogel exhibited excellent properties, such as low cytotoxicity, sustained SeNPs release, and favorable antioxidant activity. Under oxidative stress, the SeNPs/CMC/Alg hydrogel promoted reactive oxygen species (ROS) elimination and enhanced the osteogenic and proangiogenic abilities of bone marrow mesenchymal stem cells (BMSCs). After establishing a rabbit model of SONFH, the SeNPs/CMC/Alg hydrogel was transplanted into the femoral head after core decompression (CD) surgery. Radiographic and histological analyses revealed that the hydrogel treatment alleviated SONFH by eliminating ROS and promoting osteogenesis and angiogenesis compared to those in the CD and CMC/Alg groups. In vitro and in vivo studies indicated that the Wnt/β-catenin signaling pathway was activated by the SeNPs/CMC/Alg hydrogel in both hydrogen peroxide-conditioned BMSCs and necrotic femoral heads. These findings indicate that local transplantation of the SeNPs/CMC/Alg hydrogel is beneficial for treating SONFH, as it promotes ROS elimination and activation of the Wnt/β-catenin signaling pathway.

Achieving Clearance of Drug-Resistant Bacterial Infection and Rapid Cutaneous Wound Regeneration Using an ROS-Balancing-Engineered Heterojunction.

Intractable infected microenvironments caused by drug-resistant bacteria stalls the normal course of wound healing. Sono-piezodynamic therapy (SPT) is harnessed to combat pathogenic bacteria, but the superabundant reactive oxygen species (ROS) generated during SPT inevitably provoke severe inflammatory response, hindering tissue regeneration. Consequently, an intelligent nanocatalytic membrane composed of poly(lactic-co-glycolic acid) (PLGA) and black phosphorus /V2C MXene bio-heterojunctions (2D2-bioHJs) is devised. Under ultrasonication, 2D2-bioHJs effectively eliminate drug-resistant bacteria by disrupting metabolism and electron transport chain (ETC). When ultrasonication ceases, they enable the elimination of SPT-generated ROS. The 2D2-bioHJs act as a "lever" that effectively achieves a balance between ROS generation and annihilation, delivering both antibacterial and anti-inflammatory properties to the engineered membrane. More importantly, in vivo assays corroborate that the nanocatalytic membranes transform the stalled chronic wound environment into a regenerative one by eradicating the bacterial population, dampening the NF-κB inflammatory pathway and promoting angiogenesis. As envisaged, this work demonstrates a novel tactic to arm membranes with programmed antibacterial and anti-inflammatory effects to remedy refractory infected wounds from drug-fast bacteria.

Mesoporous Ternary Nanozymes with Anti‐Senescence and Anti‐Inflammation Activities for Atherosclerosis Management

AbstractNumerous anti‐inflammatory agents and corresponding therapeutic strategies have been explored for treating inflammation‐related atherosclerosis, which has struggled with compromised antiatherosclerotic efficacy due to the complex pathogenesis. The senescent endothelial cells participate fundamentally at all stages in atherosclerosis, providing the basis for developing senotherapies to blunt the deleterious effects of senescent cells. In this work, a mesoporous palladium‐boron‐phosphorus ternary nanozyme with intrinsic superoxide dismutase/catalase‐mimicking properties is rationally engineered to co‐load H2 (an anti‐inflammatory agent) within nanozyme's crystal lattice and 4,4′‐dimethoxychalcone (DIM, an anti‐senescence agent) within mesopores, which elicits strong anti‐inflammatory effect in pro‐inflammatory macrophages by elimination of reactive oxygen species (ROS), H2 anti‐inflammation and promotion of cholesterol efflux, while simultaneously exerts anti‐senescence capacity in endothelial cells by protection of DNA from ROS damage and degradation of the cellular senescent components via autophagy activation. Both in vitro and in vivo experimental results verify the synergy between nanozyme‐based anti‐inflammatory therapy and autophagy activation, demonstrating that such a precise regulation of vascular senescence is applicable to augment antiatherosclerotic efficiency, which provides the nanomedicine‐enabled and senotherapy‐based paradigm for atherosclerosis management.

Molecular docking of selected steroid compounds from Hydrilla Verticillata on human Ros1 kinase receptor

Hydrilla verticillata, an aquatic plant, contains various steroids like stigmasterol, β-sitosterol, fucosterol, cholesterol, and campesterol with potential antioxidant properties. Antioxidants protect cells and tissues from Reactive Oxygen Species (ROS)-induced damage by impeding oxidation reactions and ROS elimination. This study aimed to investigate the molecular docking results of selected steroid compounds from H. verticillata with the human ROS1 kinase receptor. Five selected steroid compounds, collected from the PubChem database. The human ROS1 kinase receptor, PDB ID 3ZBF, was obtained from the RCSB Protein Data Bank. Molecular docking of these selected steroid compounds to human ROS1 Kinase was performed, comparing their binding affinities to crizotinib (native ligand) and ascorbic acid. The docking utilized the PyRx Virtual Screening Tool and visualization via BIOVIA Discovery Studio Visualizer. Results indicated that stigmasterol, β-sitosterol, fucosterol, cholesterol, and campesterol had binding affinities of -8.1, -8.2, -8.6, -8.4, and -8.5 kcal/mol, respectively, to the 3ZBF human ROS1 kinase receptor. While, crizotinib and ascorbic acid exhibited binding affinities of -8.4 kcal/mol and -4.7 kcal/mol. Some H. verticillata steroid compounds displayed stronger binding affinities than crizotinib and ascorbic acid. Furthermore, these compounds complied with Lipinski’s and Veber’s rules and achieved bioavailability score of 0.55, suggesting their potential as antioxidants and anticancers.

A Review on Bioactive Anthraquinone and Derivatives as the Regulators for ROS.

Anthraquinones are bioactive natural products, which are often found in medicinal herbs. These compounds exert antioxidant-related pharmacological actions including neuroprotective effects, anti-inflammation, anticancer, hepatoprotective effects and anti-aging, etc. Considering the benefits from their pharmacological use, recently, there was an upsurge in the development and utilization of anthraquinones as reactive oxygen species (ROS) regulators. In this review, a deep discussion was carried out on their antioxidant activities and the structure-activity relationships. The antioxidant mechanisms and the chemistry behind the antioxidant activities of both natural and synthesized compounds were furtherly explored and demonstrated. Due to the specific chemical activity of ROS, antioxidants are essential for human health. Therefore, the development of reagents that regulate the imbalance between ROS formation and elimination should be more extensive and rational, and the exploration of antioxidant mechanisms of anthraquinones may provide new therapeutic tools and ideas for various diseases mediated by ROS.