Endogenous Reactive Oxygen Species Research Articles

AuCePt porous hollow cascade nanozymes targeted delivery of disulfiram for alleviating hepatic insulin resistance

As the pathophysiological basis of type 2 diabetes mellitus (T2DM), insulin resistance (IR) is closely related to oxidative stress (OS) and inflammation, while nanozymes have a good therapeutic effect on inflammation and OS by scavenging reactive oxygen species (ROS). Hence, AuCePt porous hollow cascade nanozymes (AuCePt PHNs) are designed by integrating the dominant enzymatic activities of three metallic materials, which exhibit superior superoxide dismutase/catalase-like activities, and high drug loading capacity. In vitro experiments proved that AuCePt PHNs can ultra-efficiently scavenge endogenous and exogenous ROS. Moreover, AuCePt PHNs modified with lactobionic acid (LA) and loaded with disulfiram (DSF), named as AuCePt PHNs-LA@DSF, can significantly improve glucose uptake and glycogen synthesis in IR hepatocytes by regulating the insulin signaling pathways (IRS-1/AKT) and gluconeogenesis signaling pathways (FOXO-1/PEPCK). Intravenous administration of AuCePt PHNs-LA@DSF not only showed high liver targeting efficiency, but also reduced body weight and blood glucose and improved IR and lipid accumulation in high-fat diet-induced obese mice and diabetic ob/ob mice. This research elucidates the intrinsic activity of AuCePt PHNs for cascade scavenging of ROS, and reveals the potential effect of AuCePt PHNs-LA@DSF in T2DM treatment.Graphical abstract

GALNT14-mediated O-glycosylation drives lung adenocarcinoma progression by reducing endogenous reactive oxygen species generation

Aberrant glycosylation, resulting from dysregulated expression of glycosyltransferases, is a prevalent feature of cancer cells. N-acetylgalactosaminyltransferase-14 (GALNT14) serves as a pivotal enzyme responsible for initiating O-GalNAcylation. It remains unclear whether and how GALNT14 affects lung adenocarcinoma (LUAD). Here, GALNT14 expression in LUAD was analyzed by searching public databases and verified by examining clinical samples. Bioinformatics, LC-MS/MS, RNA-seq, and RIP-seq analyses were used to uncover the mechanism underlying GALNT14. We observed that GALNT14 was frequently overexpressed in LUAD tissues. High GALNT14 expression was positively associated with advanced TNM stage, larger tumor size, and unfavorable prognosis. Functionally, GALNT14 facilitated LUAD cell proliferation, migration, and invasion in vitro and accelerated tumor growth in vivo. Mechanistically, GALNT14 reduced the accumulation of endogenous reactive oxygen species (ROS) to exert its oncogenic function via O-glycosylating hnRNPUL1 to upregulate AKR1C2 expression. Meanwhile, GALNT14 expression was directly modulated by miR-125a.These findings indicated that GALNT14-mediated O-GalNAcylation could drive LUAD progression via eliminating ROS and might be a valuable therapeutic target.

Self-Illuminating Copper-Luminol Coordination Polymers for Bioluminescence Imaging of Oxidative Damage.

Timely detection of reactive oxygen species (ROS) accumulated during inflammation is essential for an early disease diagnosis. Compared to fluorescence probes with limited sensitivity and accuracy, chemiluminescence (CL) imaging offers the potential for highly sensitive molecular visualization of ROS by minimizing background interferences. However, the development of bright and easily manufacturable CL probes for ROS imaging remains challenging. In this study, a novel chemiluminescent nanoprobe named Cu-Lum@NPs for ROS imaging in inflammation was synthesized by using a one-step solvothermal method. The Cu-Lum@NPs, which are composed of coordination polymers containing copper ions and luminol (Lum), demonstrate intrinsic peroxidase-like activity that relies on Cu(I) as the catalytic active center to initiate the Fenton reaction. This catalytic process facilitates the decomposition of hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) and superoxide anion radicals (O2•-), leading to the oxidation of Lum and inducing strong luminescence. Cu-Lum@NPs, displaying nanozyme characteristics, were observed to accelerate and enhance the ROS-responsive luminescence (10-1600-fold in solution and over 100-fold in neutrophils) and notably extend persistent luminescence. The Cu-Lum@NPs allowed for CL imaging of endogenous ROS in living cells and animals with an outstanding signal-to-noise ratio exceeding 96 and facilitated oxidative damage luminescence imaging for tissue-specific detection. The study presents Cu-Lum@NPs, a highly sensitive and easily manufacturable chemiluminescent nanoprobe for ROS imaging both in vitro and in vivo, exhibiting enhanced luminescence and prolonged persistence for ROS-related disease detection.

Aucubin Induces Apoptotic Cell Death Through Caspase-dependent Pathways in Human Osteosarcoma MG-63 Cells

Background Osteosarcomas (OSs) are predominantly generated by mesenchymal cells, which commonly develop in the distal and upper regions of the bones. OS has high mortality rates and treatment failures, mostly due to the presence of lung metastases. Purpose The present work aimed to scrutinize the anticancer potentials of aucubin against OS human osteosarcoma (MG-63) cells. Methods The proliferation of the control and aucubin-treated MG-63 cells was studied by an XTT assay. Various fluorescent staining assays were done to assess the endogenous reactive oxygen species (ROS) accumulation and apoptosis in the aucubin-treated MG-63 cells. The caspase-3, -8, and -9 activities were investigated using the assay kits. Results The XTT assay results confirmed that the aucubin treatment considerably reduced the MG-63 cells. The findings of the various fluorescent staining assays evidenced that the aucubin treatment remarkably promoted endogenous ROS accumulation and apoptosis in the OS cells. The caspase activities were also improved in the OS cells after the aucubin treatment. Conclusion The results of this work show that aucubin treatments inhibit cell proliferation and trigger apoptosis in MG-63 cells, suggesting its potential as a promising anticancer agent. These findings will facilitate the future development of aucubin as a talented anticancer agent to treat OS.

Ultra-Small Copper-Based Multienzyme-Like Nanoparticles Protect Against Hepatic Ischemia-Reperfusion Injury Through Scavenging Reactive Oxygen Species in Mice.

Hepatic ischemia-reperfusion injury (IRI) is a severe complication that occurs in the process of liver transplantation, hepatectomy, and other end-stage liver disease surgery, often resulting in the failure of surgery operation and even patient death. Currently, there is no effective way to prevent hepatic IRI clinically. Here, it is reported that the ultra-small copper-based multienzyme-like nanoparticles with catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) catalytic activities significantly scavenge the surge-generated endogenous reactive oxygen species (ROS) and effectively protects hepatic IRI. Density functional theory calculations confirm that the nanoparticles efficiently scavenge ROS through their synergistic effects of the ultra-small copper SOD-like activity and manganese dioxides CAT-like activity. Furthermore, the results show that the biocompatible CMP NPs significantly protected hepatocytes from IRI in vitro and in vivo. Importantly, their therapeutic effect is much stronger than that of N-acetylcysteamine acid (NAC), an FDA-approved antioxidative drug. Finally, it is demonstrated that the protective effects of CMP NPs on hepatic IRI are related to suppressing inflammation and hepatocytic apoptosis and maintaining endothelial functions through scavenging ROS in liver tissues. The study can provide insight into the development of next-generation nanomedicines for scavenging ROS.

Exogenous Reactive Oxygen Species Augments SMAD4 Expression And TGF-β Paradox in Human Breast Cancer

Background: The Transforming growth factor-β (TGF-β) functions to induce apoptosis, cell cycle arrest, and differentiation is central to sustaining tissue homeostasis and maintaining genomic stability. TGF-β normally, an effective tumor-suppressor that restricts the uncontrolled division of cells augments the development and progression of human malignancies when cytostatic activities of TGF-β are resisted by genetic and epigenetic events caused by tumorigenesis. This dichotomic nature of TGF-β during oncogenesis termed as “TGF-β Paradox,” persists to be the most crucial and puzzling query regarding its physio-pathological function and the role of cellular antioxidant status is highly interrelated which warrants more studies on the role of endogenous reactive oxygen species (ROS) in deciding epithelial-mesenchymal transition (EMT) process. The objective of the study was to check whether enhanced ROS augments the TGF-β pathway facilitating EMT. Methods: In vitro toxicity assay was performed to assess the appropriate concentration of hydrogen peroxide (H2O2) imparting oxidative stress. Comet assay and 8-OHdG (8-hydroxy-2’-deoxyguanosine) enzyme-linked immunosorbent assay (ELISA) were performed to check the extent of DNA damage and adduct production respectively. Mitogen-activated protein kinase (MAPK) p38 ELISA and mRNA gene expression analysis of TGF-β and SMAD were done to verify the effect of H2O2 on these signaling. Results: The objective of the study was to check whether enhanced ROS augments the TGF-β pathway facilitating EMT. Along with morphological alterations, a dose-dependent decrease in cell viability was seen at 300µM of H2O2 compared to 75µM. DCFDA labeling discovered the dose-dependent gradation of intracellular ROS generation and this was correlated to increased cellular DNA damage and DNA adduct production which was increased linearly with increasing H2O2 as evident with comet test and 8-OHdG ELISA. Significantly reduced MAPK p38 activity revealed by indirect ELISA analysis suggests lessened suppression of cell growth. Conclusions: The study establishes that higher intracellular ROS will facilitate the TGF-β paradox leading to epithelial mesenchymal transition which can adversely affect therapeutic strategies targeting EMT

Anti-Stress and Anti-ROS Effects of MnOx-Functionalized Thermosensitive Nanohydrogel Protect BMSCs for Intervertebral Disc Degeneration Repair.

Stem cell transplantation is proven to be a promising strategy for intervertebral disc degeneration (IDD) repair. However, replicative senescence of bone marrow-derived mesenchymal stem cells (BMSCs), shear damage during direct injection, mechanical stress, and the reactive oxygen species (ROS)-rich microenvironment in degenerative intervertebral discs (IVDs) cause significant cellular damage and limit the therapeutic efficacy. Here, an injectable manganese oxide (MnOx)-functionalized thermosensitive nanohydrogel is proposed for BMSC transplantation for IDD therapy. The MnOx-functionalized thermosensitive nanohydrogel not only successfully protects BMSCs from shear force and mechanical stress before and after injection, but also repairs the harsh high-ROS environment in degenerative IVDs, thus effectively increasing the viability of BMSCs and resident nucleus pulposus cells (NPCs). The MnOx-functionalized thermosensitive nanohydrogel provides mechanical protection for stem cells and helps to remove endogenous ROS, providing a promising stem cell delivery platform for the treatment of IDD.

Mitochondrial Plasticity and Glucose Metabolic Alterations in Human Cancer under Oxidative Stress-From Viewpoints of Chronic Inflammation and Neutrophil Extracellular Traps (NETs).

Oxidative stress elicited by reactive oxygen species (ROS) and chronic inflammation are involved both in deterring and the generation/progression of human cancers. Exogenous ROS can injure mitochondria and induce them to generate more endogenous mitochondrial ROS to further perpetuate the deteriorating condition in the affected cells. Dysfunction of these cancer mitochondria may possibly be offset by the Warburg effect, which is characterized by amplified glycolysis and metabolic reprogramming. ROS from neutrophil extracellular traps (NETs) are an essential element for neutrophils to defend against invading pathogens or to kill cancer cells. A chronic inflammation typically includes consecutive NET activation and tissue damage, as well as tissue repair, and together with NETs, ROS would participate in both the destruction and progression of cancers. This review discusses human mitochondrial plasticity and the glucose metabolic reprogramming of cancer cells confronting oxidative stress by the means of chronic inflammation and neutrophil extracellular traps (NETs).

Development of ROS-sensitive capofungin hydrogel by crosslinking chitosan with four-arm polyethylene glycol derivative for treatment of vulvovaginal candidiasis

Both exogenous and endogenous reactive oxygen species (ROS) in vulvovaginal candidiasis (VVC) play pivotal roles in promoting the hyphal formation of Candida albicans (CA), which suggests that clearing ROS could inhibit CA hyphae formation. A ROS-sensitive hydrogel (CAS@4Arm-PB/CS) was formulated by using a novel four-arm polyethylene glycol (4Arm-PEG) derivative (4Arm-PB) as a crosslinking agent, chitosan (CS) as the hydrogel matrix, and caspofungin (CAS) as the antifungal drug against CA. The ROS-sensitivity, disintegration mechanism, crosslinking action, swelling degree, microstructure, modulus, and rheological properties of 4Arm-PB were characterized. According to the results, 5.0 % 4Arm-PB could quickly and efficiently cross-link 0.5 mg/mL of CS. The ROS-sensitivity of 4Arm-PB was 10–50 μM, indicating a strong ROS sensitivity. The in vitro and in vivo anti-CA results indicated that CAS@4Arm-PB/CS not only cleared endogenous and exogenous ROS and inhibited the formation of CA hyphae and biofilm but also contributed beneficially to the treatment of VVC mice caused by CA infection, implying a certain safety aspect and an in vivo applicability. This research introduces a novel functional crosslinking agent for CS hydrogel formulation, presenting a new avenue for hydrogel-based drug delivery systems and therapeutic strategies for VVC treatment.

Absence of mitochondrial CX9C-CX10C protein Cox12 generates oxidative and nitrosative stress in Saccharomyces cerevisiae: Implication on cellular redox homeostasis

Mitochondrial intermembrane space (IMS) harbors a series of small, evolutionarily conserved redox-active cysteine-rich proteins. These proteins are essential for the functioning of cytochrome c oxidase, but their role in maintaining cellular redox processes is unknown. Here, we find out that in the absence of two such cysteine-rich Cx9C-Cx10C proteins, cytochrome c oxidase subunit 12 (Cox12) or cytochrome c oxidase assembly factor 6 (Coa6), Saccharomyces cerevisiae cells become sensitive under the oxidative and nitrosative stress. Interestingly, knockout of COX12 generates a significant amount of endogenous reactive oxygen species (ROS) and reactive nitrogen species (RNS) as evidenced by FACS analysis. Moreover, cellular redox status, redox-active enzymes glutathione reductase, catalase, S-nitroso glutathione reductase, and protein nitration were significantly affected in Cox12 null cells. Further, we found that an overexpression of COX12 partially protects mitochondrial respiratory subunit Sdh2 under oxidative and nitrosative stress. Taken together, we provide proof of evidence that cysteine-rich proteins in the IMS dynamically control the cellular redox milieu and actively prevent reactive nitrogen and oxygen species generation.

Upconversion nanoparticles-CuMnO2 nanoassemblies for NIR-excited imaging of reactive oxygen species in vivo

Here, we designed a ratiometric luminescent nanoprobe based on lanthanide-doped upconversion nanoparticles-CuMnO2 nanoassemblies for rapid and sensitive detection of reactive oxygen species (ROS) levels in living cells and mouse. CuMnO2 nanosheets exhibit a wide absorption range of 300–700 nm, overlapping with the visible-light emission of upconversion nanoparticles (UCNPs), resulting in a significant upconversion luminescence quenching. In an acidic environment, H2O2 can promote the redox reaction of CuMnO2, leading to its dissociation from the surface of UCNPs and the restoration of upconversion luminescence. The variation in luminescence intensity ratio (UCL475/UCL450) were monitored to detect ROS levels. The H2O2 nanoprobe exhibited a linear response in the range of 0.314–10 μM with a detection limit of 11.3 nM. The biological tests proved the excellent biocompatibility and low toxicity of obtained UCNPs-CuMnO2 nanoassemblies. This ratiometric luminescent nanoprobe was successfully applied for the detection of exogenous and endogenous ROS in live cells as well as in vivo ROS quantitation. The dual transition metal ions endow this probe efficient catalytic decomposition capabilities, and this sensing strategy broadens the application of UCNPs-based nanomaterials in the field of biological analysis and diagnosis.

Tumor Microenvironment Reprogrammed Bimetallic Hybrid Nanostimulator for Triggering Radio-Cuproptosis-Immunotherapy.

Radio-immunotherapy driven by radiation-induced immunogenic cell death (ICD) is emerging as a potential opportunity to address conventional radiotherapy (RT) that is only applicable to localized tumor treatment. However, the effective activation of ICD during RT is severely limited by radiation dose, weak tumor immunogenicity, and radio-resistance caused by tumor microenvironment (TME). Herein, a novel bimetallic hybrid nanoscale coordination nanostimulator is first proposed by phosphate backbone doped with copper ions (Cu2+) and hafnium ions (Hf4+), and then modified with polyvinylpyrrolidone (PVP). The PVPylated Cu/Hf-doped phosphate nanostimulator (denoted as CHP) exhibits effective reprogramming of TME, including depletion of tumor endogenous glutathione (GSH), relief of tumor hypoxia and repolarization of M2 phenotypic macrophages, thus achieving tumor radiosensitization at low X-ray irradiation dose, gradually accumulation of tumor endogenous reactive oxygen species (ROS) and augmenting cuproptosis. In addition, cuproptosis can amplify RT-induced anti-tumor immunity through ICD activation, ultimately resulting in a robust anti-tumor immune response and long-term immunity, evidenced by distant tumor growth inhibition of 4T1-tumor-bearing models. More interestingly, it is discovered that CHP-mediated cuproptosis can be intensifiable during X-ray irradiation. Taken together, this work presents a novel radio-cuproptosis-immunotherapy cascade strategy, offering a new perspective for innovation in the treatment field of breast cancer.

Enzyme-Dynamic Extracellular Vesicles for Metalloimmunotherapy of Malignant Pleural Effusions.

Malignant pleural effusions (MPEs) are hard to treat, and their onset usually signals terminal cancer. Immunotherapies hold promise but must overcome the immunosuppressive MPE microenvironment. Herein, we treat MPEs via synergistically combining two emerging cancer therapy modalities: enzyme-dynamic therapy (EDT) and metalloimmunotherapy. To do so, a nanoplatform termed "A-R-SOME" was developed which comprises MPE-targeted M1 type extracellular vesicles (EVs) loaded with (1) a manganese-based superoxide dismutase (SOD) enzyme, (2) stimulator of interferon genes (STING) agonist diABZI-2, and (3) signal transducer and an activator of transcription 3 (STAT3) small interfering RNA. Endogenous reactive oxygen species within tumors induced immunogenic cell death by EDT, along with STING activation by both Mn and diABZI-2, and suppression of the STAT3 pathway. Systemically administered A-R-SOME alleviated the MPE immunosuppressive microenvironment, triggered antitumor systemic immunity, and long-term immune memory, leading to the complete eradication of MPE and pleural tumors with 100% survival rate in an aggressive murine model. A-R-SOME-induced immune effects were also observed in human patient-derived MPE, pointing toward the translation potential of A-R-SOME as an experimental malignancy treatment.

Peroxiredoxin 2 regulates DAF-16/FOXO mediated mitochondrial remodelling in response to exercise that is disrupted in ageing

ObjectivesA decline in mitochondrial function and increased susceptibility to oxidative stress is a hallmark of ageing. Exercise endogenously generates reactive oxygen species (ROS) in skeletal muscle and promotes mitochondrial remodelling resulting in improved mitochondrial function. It is unclear how exercise induced redox signalling results in alterations in mitochondrial dynamics and morphology. MethodsIn this study, a Caenorhabditis elegans model of exercise and ageing was used to determine the mechanistic role of Peroxiredoxin 2 (PRDX-2) in regulating mitochondrial morphology. Mitochondrial morphology was analysed using transgenic reporter strains and transmission electron microscopy, complimented with the analysis of the effects of ageing and exercise on physiological activity. ResultsThe redox state of PRDX-2 was altered with exercise and ageing, hyperoxidised peroxiredoxins were detected in old worms along with basally elevated intracellular ROS. Exercise generated intracellular ROS and rapid mitochondrial remodelling, which was disrupted with age. The exercise intervention promoted mitochondrial ER contact sites (MERCS) assembly and increased DAF-16/FOXO nuclear localisation. The prdx-2 mutant strain had a disrupted mitochondrial network as evidenced by increased mitochondrial fragmentation. In the prdx-2 mutant strain, exercise did not activate DAF-16/FOXO, mitophagy or increase MERCS assembly. The results demonstrate that exercise generated ROS increased DAF-16/FOXO transcription factor nuclear localisation required for activation of mitochondrial fusion events that were blunted with age. ConclusionsThe data demonstrate the critical role of PRDX-2 in orchestrating mitochondrial remodelling in response to a physiological stress by regulating redox dependent DAF-16/FOXO nuclear localisation.

Triterpene-Based Prodrug for Self-Boosted Drug Release and Targeted Oral Squamous Cell Carcinoma Chemotherapy.

Chemotherapy is one of the main treatments for oral squamous cell carcinoma (OSCC), especially as a combined modality approach with and after surgery or radiotherapy. Limited therapeutic efficiency and serious side effects greatly restrict the clinical performance of chemotherapeutic drugs. The development of smart nanomedicines has provided new research directions, to some extent. However, the involvement of complex carrier compositions inevitably brings biosafety concerns and greatly limits the "bench-to-bed" translation of most nanomedicines reported. In this study, a carrier-free self-assembled prodrug was fabricated by two triterpenes (glycyrrhetinic acid, GA and ginsenoside Rh2, Rh2) isolated from medicinal plants, licorice, and ginseng, for the targeted and highly effective treatment of OSCC. Reactive oxygen species (ROS) self-supplied molecule TK-GA2 was synthesized with ROS-responsive thioketal linker and prodrug was prepared by a rapid-solvent-exchange method with TK-GA2 and Rh2. After administration, oral tumor cells transported large amounts of prodrugs with glucose ligands competitively. Endogenous ROS in oral tumor cells then promoted the release of GA and Rh2. GA further evoked the generation of a large number of ROS to help self-boosted drug release and increase oxidative stress, synergistically causing tumor cell apoptosis with Rh2. Overall, this carrier-free triterpene-based prodrug might provide a preeminent opinion on the design of effective chemotherapeutics with low systemic toxicity against OSCC.

Endogenous and exogeneous stimuli-triggered reactive oxygen species evoke long-lived carbon monoxide to fight against lung cancer

Reactive oxygen species (ROS)-associated anticancer approaches usually suffer from two limitations, i.e., insufficient ROS level and short ROS half-life. Nevertheless, no report has synchronously addressed both concerns yet. Herein, a multichannel actions-enabled nanotherapeutic platform using hollow manganese dioxide (H-MnO2) carriers to load chlorin e6 (Ce6) sonosensitizer and CO donor (e.g., Mn2(CO)10) has been constructed to maximumly elevate ROS level and trigger cascade catalysis to produce CO. Therein, intratumoral H2O2 and ultrasound as endogenous and exogeneous triggers stimulate H-MnO2 and Ce6 to produce •OH and 1O2, respectively. The further cascade reaction between ROS and Mn2(CO)10 proceeds to release CO, converting short-lived ROS into long-lived CO. Contributed by them, such a maximumly-elevated ROS accumulation and long-lived CO release successfully suppresses the progression, recurrence and metastasis of lung cancer with a prolonged survival rate. More significantly, proteomic and genomic investigations uncover that the CO-induced activation of AKT signaling pathway, NRF-2 phosphorylation and HMOX-1 overexpression induce mitochondrial dysfunction to boost anti-tumor consequences. Thus, this cascade catalysis strategy can behave as a general means to enrich ROS and trigger CO release against refractory cancers.Graphic

Novel mandelic acid derivatives containing piperazinyls as potential candidate fungicides against Monilinia fructicola: Design, synthesis and mechanism study

Brown rot of stone fruit, a disease caused by the ascomycete fungus Monilinia fructicola, has caused significant losses to the agricultural industry. In order to explore and discover potential fungicides against M. fructicola, thirty-one novel mandelic acid derivatives containing piperazine moieties were designed and synthesized based on the amide skeleton. Among them, target compound Z31 exhibited obvious in vitro antifungal activity with the EC50 value of 11.8 mg/L, and significant effects for the postharvest pears (79.4 % protective activity and 70.5 % curative activity) at a concentration of 200 mg/L. Antifungal activity for the target compounds was found to be significantly improved by the large steric hindrance of the R1 groups and the electronegative of the piperazines in the molecular structure, according to a three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis. Further mechanism studies have demonstrated that the compound Z31 can disrupt cell membrane integrity, resulting in increased membrane permeability, release of intracellular electrolytes, and affect the normal growth of hyphae. Additional, morphological study also indicated that Z31 may disrupt the integrity of the membrane by inducing generate excess endogenous reactive oxygen species (ROS) and resulting in the peroxidation of cellular lipids, which was further verified by the detection of malondialdehyde (MDA) content. These studies have provided the basis for the creation of novel fungicides to prevent brown rot in stone fruits.

Rescue of nucleus pulposus cells from an oxidative stress microenvironment via glutathione-derived carbon dots to alleviate intervertebral disc degeneration

The senescence of nucleus pulposus (NP) cells (NPCs), which is induced by the anomalous accumulation of reactive oxygen species (ROS), is a major cause of intervertebral disc degeneration (IVDD). In this research, glutathione-doped carbon dots (GSH-CDs), which are novel carbon dot antioxidant nanozymes, were successfully constructed to remove large amounts of ROS for the maintenance of NP tissue at the physical redox level. After significantly scavenging endogenous ROS via exerting antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity, GSH-CDs with good biocompatibility have been demonstrated to effectively improve mitochondrial dysfunction and rescue NPCs from senescence, catabolism, and inflammatory factors in vivo and in vitro. In vivo imaging data and histomorphological indicators, such as the disc height index (DHI) and Pfirrmann grade, demonstrated prominent improvements in the progression of IVDD after the topical application of GSH-CDs. In summary, this study investigated the GSH-CDs nanozyme, which possesses excellent potential to inhibit the senescence of NPCs with mitochondrial lesions induced by the excessive accumulation of ROS and improve the progression of IVDD, providing potential therapeutic options for clinical treatment.Graphical

Nano-enzyme hydrogels for cartilage repair effectiveness based on ternary strategy therapy.

Designing artificial nano-enzymes for scavenging reactive oxygen species (ROS) in chondrocytes (CHOs) is considered the most feasible pathway for the treatment of osteoarthritis (OA). However, the accumulation of ROS due to the amount of nano-enzymatic catalytic site exposure and insufficient oxygen supply seriously threatens the clinical application of this therapy. Although metal-organic framework (MOF) immobilization of artificial nano-enzymes to enhance active site exposure has been extensively studied, artificial nano-enzymes/MOFs for ROS scavenging in OA treatment are still lacking. In this study, a biocompatible lubricating hydrogel-loaded iron-doped zeolitic imidazolate framework-8 (Fe/ZIF-8/Gel) centrase was engineered to scavenge endogenous overexpressed ROS synergistically generating dissolved oxygen and enhancing sustained lubrication for CHOs as a ternary artificial nano-enzyme. This property enabled the nano-enzymatic hydrogels to mitigate OA hypoxia and inhibit oxidative stress damage successfully. Ternary strategy-based therapies show excellent cartilage repair in vivo. The experimental results suggest that nano-enzyme-enhanced lubricating hydrogels are a potentially effective OA treatment and a novel strategy.

Lignin-Based Antioxidant Hydrogel Patch for the Management of Atopic Dermatitis by Mitigating Oxidative Stress in the Skin.

Atopic dermatitis (AD), a chronic skin condition characterized by itching, redness, and inflammation, is closely associated with heightened levels of endogenous reactive oxygen species (ROS) in the skin. ROS can contribute to the onset and progression of AD through oxidative stress, which leads to the release of proinflammatory cytokines, T-cell differentiation, and the exacerbation of skin symptoms. In this study, we aim to develop a therapeutic antioxidant hydrogel patch for the potential treatment of AD using lignin, a biomass waste material. Lignin contains polyphenol groups that enable it to scavenge ROS and exhibit antioxidant properties. The lignin hydrogel patches, possessing optimized mechanical properties through the control of the lignin and cross-linker ratio, demonstrated high ROS-scavenging capabilities. Furthermore, the lignin hydrogel demonstrated excellent biocompatibility with the skin, exhibiting beneficial properties in protecting human keratinocytes under high oxidative conditions. When applied to an AD mouse model, the hydrogel patch effectively reduced epidermal thickness in inflamed regions, decreased mast cell infiltration, and regulated inflammatory cytokine levels. These findings collectively suggest that lignin serves as a therapeutic hydrogel patch for managing AD by modulating oxidative stress through its ROS-scavenging ability.