RESUMEN

Osteomyelitis is an osseous infectious disease that primarily affects children and the elderly with high morbidity and recurrence. The conventional treatments of osteomyelitis contain long-term and high-dose systemic antibiotics with debridements, which are not effective and lead to antibiotic resistance with serious side/adverse effects in many cases. Hence, developing novel antibiotic-free interventions against osteomyelitis (especially antibiotic-resistant bacterial infection) is urgent and anticipated. Here, a bone mesenchymal stem cell membrane-constructed nanocell (CFE@CM) was fabricated against osteomyelitis with the characteristics of acid-responsiveness, hydrogen peroxide self-supplying, enhanced chemodynamic therapeutic efficacy, bone marrow targeting and cuproptosis induction. Notably, mRNA sequencing was applied to unveil the underlying biological mechanisms and found that the biological processes related to copper ion binding, oxidative phosphorylation, peptide biosynthesis and metabolism, etc., were disturbed by CFE@CM in bacteria. This work provided an innovative antibiotic-free strategy against osteomyelitis through copper-enhanced Fenton reaction and distinct cuproptosis, promising to complement the current insufficient therapeutic regimen in clinic.

Asunto(s)

Cobre , Osteomielitis , Osteomielitis/tratamiento farmacológico , Animales , Cobre/química , Cobre/farmacología , Concentración de Iones de Hidrógeno , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Ratones , Peróxido de Hidrógeno/metabolismo , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/química , Humanos , Staphylococcus aureus/efectos de los fármacos

RESUMEN

Numerous nanoparticles have been utilized to deliver Fe2+ for tumor ferroptosis therapy, which can be readily converted to Fe3+via Fenton reactions to generate hydroxyl radical (•OH). However, the ferroptosis therapeutic efficacy of large tumors is limited due to the slow conversion of Fe3+ to Fe2+via Fenton reactions. Herein, a strategy of intratumor Fe3+/2+ cyclic catalysis is proposed for ferroptosis therapy of large tumors, which was realized based on our newly developed hollow mesoporous iron sesquioxide nanoparticle (HMISN). Cisplatin (CDDP) and Gd-poly(acrylic acid) macrochelates (GP) were loaded into the hollow core of HMISN, whose surface was modified by laccase (LAC). Fe3+, CDDP, GP, and LAC can be gradually released from CDDP@GP@HMISN@LAC in the acidic tumor microenvironment. The intratumor O2 can be catalyzed into superoxide anion (O2•-) by LAC, and the intratumor NADPH oxidases can be activated by CDDP to generate O2•-. The O2•- can react with Fe3+ to generate Fe2+, and raise H2O2 level via the superoxide dismutase. The generated Fe2+ and H2O2 can be fast converted into Fe3+ and •OH via Fenton reactions. The cyclic catalysis of intratumor Fe3+/2+ initiated by CDDP@GP@HMISN@LAC can be used for ferroptosis therapy of large tumors.

Asunto(s)

Ferroptosis , Hierro , Ferroptosis/efectos de los fármacos , Animales , Catálisis , Humanos , Hierro/química , Línea Celular Tumoral , Nanopartículas/química , Porosidad , Ratones , Cisplatino/química , Cisplatino/uso terapéutico , Neoplasias/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Ratones Endogámicos BALB C , Peróxido de Hidrógeno/química , Microambiente Tumoral/efectos de los fármacos , Ratones Desnudos , Femenino

RESUMEN

The 3,3',5,5'-tetramethylbenzidine-H2O2 (TMB-H2O2) platform has gained widespread use for rapid detection of various analytes in foods. However, the existing TMB-H2O2 platforms suffer from limited accuracy, as their signal output is confined to the visible region, which is prone to interference from various food colorants in real samples. To address this challenge, a novel Au@Os-mediated TMB-H2O2 platform is developed for both rapid and accurate detection of analytes in foods. The prepared Au@Os NPs exhibit remarkable peroxidase-like activity, making the platform display dual absorption peaks in visible and near-infrared (NIR) regions, respectively. This Au@Os-mediated TMB-H2O2 platform exhibited three linear ranges across different concentrations of ziram from 1-100, 150-600, and 800-2000 nM with limit of detection (LOD) 7.9 nM and limit of quantification (LOQ) 24.15 nM respectively. Further, the Au@Os-mediated TMB-H2O2 platform was also used for rapid and accurate detection of ziram in real food samples like apple, tomato, and black tea.

Asunto(s)

Contaminación de Alimentos , Oro , Peróxido de Hidrógeno , Límite de Detección , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/análisis , Oro/química , Contaminación de Alimentos/análisis , Bencidinas/química , Malus/química , Solanum lycopersicum/química , Té/química , Nanopartículas del Metal/química , Colorantes de Alimentos/análisis

RESUMEN

Low fluorescence under visible light excitation and catalytic activity limit many applications of graphene quantum dots in optical detection, biosensing, catalysis and biomedical. The paper reports design and synthesis of histidine, serine and folic acid-functionalized and boron and iron-doped graphene quantum dot (Fe/B-GQD-HSF). The Fe/B-GQD-HSF shows excellent fluorescence behavior and peroxidase-like activity. Excitation of 330 nm ultraviolet light produces the strongest blue fluorescence and excitation of 480 nm visible light produces the strongest yellow fluorescence. The specific activity reaches 92.67 U g-1, which is higher than that of other graphene quantum dots. The Fe/B-GQD-HSF can catalyze oxidation of 3,3',5,5'-tetramethylbenzidine with H2O2 to form blue compound. Based on this, it was used for colorimetric and fluorescence detection of H2O2. The absorbance at 652 nm linearly increases with the increase of H2O2 concentration between 0.5 and 100 µM with detection limit of 0.43 µM. The fluorescence signal linearly decreases with the increase of H2O2 concentration between 0.05 and 100 µM with detection limit of 0.035 µM. The analytical method has been satisfactorily applied in detection of H2O2 in food. The study also paves one way for design and synthesis of functional graphene quantum dots with ideal fluorescence behavior and catalytic activity.

Asunto(s)

Boro , Colorimetría , Ácido Fólico , Grafito , Histidina , Peróxido de Hidrógeno , Hierro , Puntos Cuánticos , Serina , Puntos Cuánticos/química , Grafito/química , Peróxido de Hidrógeno/análisis , Peróxido de Hidrógeno/química , Colorimetría/métodos , Ácido Fólico/análisis , Ácido Fólico/química , Hierro/análisis , Hierro/química , Boro/química , Histidina/análisis , Histidina/química , Serina/análisis , Serina/química , Espectrometría de Fluorescencia/métodos , Límite de Detección , Análisis de los Alimentos/métodos , Peroxidasa/química , Peroxidasa/metabolismo , Catálisis

RESUMEN

Fenton and Fenton-like processes, which could produce highly reactive species to degrade organic contaminants, have been widely used in the field of wastewater treatment. Therein, the chemistry of Fenton process including the nature of active oxidants, the complicated reactions involved, and the behind reason for its strongly pH-dependent performance, is the basis for the application of Fenton and Fenton-like processes in wastewater treatment. Nevertheless, the conflicting views still exist about the mechanism of the Fenton process. For instance, reaching a unanimous consensus on the nature of active oxidants (hydroxyl radical or tetravalent iron) in this process remains challenging. This review comprehensively examined the mechanism of the Fenton process including the debate on the nature of active oxidants, reactions involved in the Fenton process, and the behind reason for the pH-dependent degradation of contaminants in the Fenton process. Then, we summarized several strategies that promote the Fe(II)/Fe(III) cycle, reduce the competitive consumption of active oxidants by side reactions, and replace the Fenton reagent, thus improving the performance of the Fenton process. Furthermore, advances for the future were proposed including the demand for the high-accuracy identification of active oxidants and taking advantages of the characteristic of target contaminants during the degradation of contaminants by the Fenton process.

Asunto(s)

Peróxido de Hidrógeno , Hierro , Eliminación de Residuos Líquidos , Hierro/química , Peróxido de Hidrógeno/química , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Aguas Residuales/química , Oxidación-Reducción , Radical Hidroxilo/química

RESUMEN

We address the targeted destruction of Karenia brevis using the algaecide calcium peroxide, in tandem with the flocculation and sinking of the species. The specific aspect of the approach is the incorporation of the algaecide within the floc to rapidly kill K. brevis, thus minimizing escape of cells from the floc and reentry to the water column. CaO2 gradually produces H2O2, which diffuses through cell membranes and induces oxidative stress, leading to cell death via excessive reactive oxygen species (ROS) formation. The effect of varying doses of calcium peroxide on K. brevis cells was measured with pulse amplitude modulated fluorometry and indicated that doses as low as 30 mg/L when integrated into flocs are effective in suppressing photosynthesis. Cell viability assays also indicate that such low levels are sufficient to cause cell death in a 3-6 hour time period. Thus, the proposed technology involving the incorporation of calcium peroxide in a cationic flocculating agent (polyaluminum chloride, PAC) leads to an inexpensive and scalable technology to mitigate harmful algal blooms of K. brevis.

Asunto(s)

Dinoflagelados , Peróxidos , Dinoflagelados/fisiología , Dinoflagelados/efectos de los fármacos , Floculación , Floraciones de Algas Nocivas , Hidróxido de Aluminio/farmacología , Hidróxido de Aluminio/química , Óxidos/farmacología , Peróxido de Hidrógeno , Especies Reactivas de Oxígeno/metabolismo , Fotosíntesis/efectos de los fármacos

RESUMEN

The Chinese bayberry pomace wine (CPW) was prepared with the assisted fermentation of lactic acid bacteria and acetic acid bacteria, and its antioxidant effect on Drosophila melanogaster was researched. After mixed fermentation, CPW had a better color, which means there was more retention of anthocyanins, and the functional activity of anthocyanins could enhance the antioxidant capacity of flies. We found that the lifespan of flies exposed to CPW was prolonged, and the reproductive capacity of these flies was decreased. The food intake of flies was also influenced by CPW with gender differences. Furthermore, CPW alleviated the excessive proliferation of the intestinal precursor cells of H2O2-induced flies and activated the transcription level of antibacterial peptide genes. CPW had a protective effect on H2O2-induced acute injury flies, with an increased survival rate, enhanced SOD and CAT activities, and decreased malondialdehyde (MDA) content in flies. The expression of oxidative stress-related genes including CuZn-SOD, Mn-SOD, and CAT was also significantly upregulated by CPW, but the downregulation effect of CPW on age-related gene expression such as methuselah (MTH), the target of rapamycin (TOR) and ribosomaiprotein S6 kinase (S6K) was sex-specific. These results suggested that CPW played an important role in anti-oxidative stress injury, which was beneficial to promoting the reuse of by-products from Chinese bayberry processing.

Asunto(s)

Antioxidantes , Drosophila melanogaster , Fermentación , Myrica , Estrés Oxidativo , Vino , Animales , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/metabolismo , Estrés Oxidativo/efectos de los fármacos , Vino/análisis , Antioxidantes/farmacología , Antioxidantes/metabolismo , Masculino , Femenino , Myrica/química , Longevidad/efectos de los fármacos , Antocianinas/farmacología , Peróxido de Hidrógeno/metabolismo , Frutas/química , Pueblos del Este de Asia

RESUMEN

Salinity is the major abiotic stress among others that determines crop productivity. The primary goal is to examine the impact of Zinc Oxide Nanoparticles (ZnO NPs) on the growth, metabolism, and defense systems of pea plants in simulated stress conditions. The ZnO NPs were synthesized via a chemical process and characterized by UV, XRD, and SEM. The ZnO NPs application (50 and 100) ppm and salt (50 mM and 100 mM) concentrations were carried out individually and in combination. At 50 ppm ZnO NPs the results revealed both positive and negative effects, demonstrating an increase in the root length and other growth parameters, along with a decrease in Malondialdehyde (MDA) and hydrogen peroxide concentrations. However, different concentrations of salt (50 mM and 100 mM) had an overall negative impact on all assessed parameters. In exploring the combined effects of ZnO NPs and salt, various concentrations yielded different outcomes. Significantly, only 50 mM NaCl combined with 50 ppm ZnO NPs demonstrated positive effects on pea physiology, leading to a substantial increase in root length and improvement in other physiological parameters. Moreover, this treatment resulted in decreased levels of MAD, Glycine betaine, and hydrogen peroxide. Conversely, all other treatments exhibited negative effects on the assessed parameters, possibly due to the high concentrations of both stressors. The findings offered valuble reference data for research on the impact of salinity on growth parameters of future agriculture crop.

Asunto(s)

Pisum sativum , Estrés Salino , Óxido de Zinc , Óxido de Zinc/farmacología , Pisum sativum/efectos de los fármacos , Pisum sativum/crecimiento & desarrollo , Pisum sativum/fisiología , Pisum sativum/metabolismo , Estrés Salino/efectos de los fármacos , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Raíces de Plantas/fisiología , Malondialdehído/metabolismo , Peróxido de Hidrógeno/metabolismo , Nanopartículas del Metal , Nanopartículas , Salinidad

RESUMEN

BACKGROUND: Staphylococcus aureus is an infectious bacterium that is frequently found in healthcare settings and the community. This study aimed to prepare rutin-loaded chitosan nanoparticles (Rut-CS NPs) and assess their antibacterial activity against pathogenic strains of S. aureus. RESULTS: The synthesized Rut-CS NPs exhibited an amorphous morphology with a size ranging from 160 to 240 nm and a zeta potential of 37.3 mV. Rut-CS NPs demonstrated significant antibacterial activity against S. aureus strains. Following exposure to Rut-CS NPs, the production of staphyloxanthin pigment decreased by 43.31-89.63%, leading to increased susceptibility of S. aureus to hydrogen peroxide. Additionally, visual inspection of cell morphology indicated changes in membrane integrity and permeability upon Rut-CS NPs exposure, leading to a substantial increase (107.07-191.08%) in cytoplasmic DNA leakage in the strains. Furthermore, ½ MIC of Rut-CS NPs effectively inhibited the biofilm formation (22.5-37.5%) and hemolytic activity (69-82.59%) in the S. aureus strains. CONCLUSIONS: Our study showcases that Rut-CS NPs can serve as a novel treatment agent to combat S. aureus infections by altering cell morphology and inhibiting virulence factors of S. aureus.

Asunto(s)

Antibacterianos , Biopelículas , Quitosano , Pruebas de Sensibilidad Microbiana , Nanopartículas , Rutina , Staphylococcus aureus , Xantófilas , Staphylococcus aureus/efectos de los fármacos , Quitosano/farmacología , Quitosano/química , Rutina/farmacología , Rutina/química , Nanopartículas/química , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas/efectos de los fármacos , Xantófilas/farmacología , Xantófilas/química , Hemólisis/efectos de los fármacos , Factores de Virulencia , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Humanos , Peróxido de Hidrógeno/farmacología

RESUMEN

Climate change-induced drought stress decreases crop productivity, but the application of ß-sitosterol (BS) and biochar (BC) boosts crop growth and yield. A pot experiment was conducted to examine the effects of the alone and combined application of BS and BC on the growth and yield of Phaseolus vulgaris under drought stress. The synergistic application of BS and BC increased plant height (46.9cm), shoot dry weight (6.9g/pot), and root dry weight (2.5g/pot) of P. vulgaris plants under drought stress. The trend of applied treatments for photosynthetic rate remained as BC (15%)

Asunto(s)

Carbón Orgánico , Sequías , Phaseolus , Sitoesteroles , Sitoesteroles/farmacología , Phaseolus/efectos de los fármacos , Phaseolus/fisiología , Phaseolus/crecimiento & desarrollo , Carbón Orgánico/farmacología , Valor Nutritivo , Estrés Fisiológico/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Malondialdehído/metabolismo , Resistencia a la Sequía

RESUMEN

Textile wastewater, laden with persistent dyes and non-biodegradable organics, poses a challenge for treatment in common effluent treatment plants (CETPs) using conventional methods. Pre-treatment of textile effluents is essential to ensure compatibility with CETPs. The present study employed three-dimensional (3D) aluminum and graphite electrodes for a sequential electro-coagulation and electro-Fenton (EC + EF) process. An experimental plan of 25 experiments was constructed using Taguchi method. The combination resulted in high removal efficiencies: 99.91% for color, 93.20% for chemical oxygen demand (COD), and 91.75% for total organic carbon (TOC) for the operating parameters; for EC, current density (J): 20 mA/cm2, time (t): 45 min, speed of rotation (N): 55 rpm; and for EF, current density (J): 25 mA/cm2, time (t): 50 min, iron concentration: 40 mg/L. Post-treatment, the wastewater exhibited an enhanced biodegradability index of 0.875, rendering it suitable for CETPs. There was an increase of 11% in the total energy consumption when energy spent during rotation and aeration at the time of EC and EF, respectively, were considered. This energy increases the cost and is not accounted for, in previous research. The energy consumption in kWh per g of COD removed at optimum condition for the hybrid treatment was 0.0314, which is lower than the energy consumption by other electrochemical processes employing plate electrodes. This indicates that 3D electrodes are more energy efficient than plate electrodes. PRACTITIONER POINTS: Hybrid electrochemical processes can be used as pre-treatment method for textile effluents. Three-dimensional electrodes improve removal rates with lower energy consumption. Significant color, COD, and TOC abatement were noted post-hybrid treatment of textile wastewater. Biodegradability of the textile effluent improves after the hybrid treatment.

Asunto(s)

Hierro , Eliminación de Residuos Líquidos , Aguas Residuales , Contaminantes Químicos del Agua , Aguas Residuales/química , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/química , Hierro/química , Industria Textil , Residuos Industriales , Técnicas Electroquímicas/métodos , Peróxido de Hidrógeno/química , Textiles , Purificación del Agua/métodos , Análisis de la Demanda Biológica de Oxígeno

RESUMEN

BACKGROUND: Dysfunction of the cholinergic system and increased oxidative stress have a crucial role in cognitive disorders including Alzheimer's disease (AD). Here, we have investigated the protective effects of betanin, a novel acetylcholinesterase (AChE) inhibitor, on hydrogen peroxide (H2O2)-induced cell death in PC12 cells. METHODS AND RESULTS: The protective effects were assessed by measuring cell viability, the amount of reactive oxygen species (ROS) production, AChE activity, cell damage, and apoptosis using resazurin, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), Ellman method, lactate dehydrogenase (LDH) release, propidium iodide (PI) staining and flow cytometry, and Western blot analysis. H2O2 (150 µM) resulted in cell viability reduction and apoptosis induction while, pretreatment with the betanin (10, 20, and 50 µM) and N-Acetyl-L-cysteine (NAC) (2.5 and 5 mM) significantly increased the viability (P < 0.05, P < 0.01 and P < 0.001) and at 5-50 µM betanin decreased ROS amount (P < 0.05, P < 0.01 and P < 0.001). Whereas, pretreatment with the betanin (10, 20, and 50 µM) decreased AChE activity (P < 0.001), also at 20 and 50 µM betanin reduced the release of LDH (P < 0.001), and at 10-50 µM decreased the percentage of apoptotic cells (P < 0.001). Apoptosis biomarkers such as cleaved poly (ADP-ribose) polymerase (PARP) (P < 0.01 and P < 0.001) and cytochrome c (P < 0.05 and P < 0.001) were attenuated after pretreatment of PC12 cells with betanin at 10-20 µM and 10-50 µM respectively. Indeed, survivin (P < 0.001) increased after pretreatment of cells with betanin at 10-20 µM. CONCLUSIONS: Overall, betanin may use the potential to delay or prevent cell death caused by AD through decreasing the activity of AChE as well as attenuating the expression of proteins involved in the apoptosis pathway.

Asunto(s)

Acetilcolinesterasa , Apoptosis , Betacianinas , Supervivencia Celular , Inhibidores de la Colinesterasa , Peróxido de Hidrógeno , Estrés Oxidativo , Especies Reactivas de Oxígeno , Células PC12 , Animales , Ratas , Apoptosis/efectos de los fármacos , Inhibidores de la Colinesterasa/farmacología , Peróxido de Hidrógeno/farmacología , Especies Reactivas de Oxígeno/metabolismo , Betacianinas/farmacología , Supervivencia Celular/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Acetilcolinesterasa/metabolismo , Fármacos Neuroprotectores/farmacología

RESUMEN

In plants, a local infection can lead to systemic acquired resistance (SAR) through increased production of salicylic acid (SA). For many years, the identity of the mobile signal and its direct transduction mechanism for systemic SA synthesis in initiating SAR have been debated. We found that in Arabidopsis thaliana, after a local infection, the conserved cysteine residue of the transcription factor CCA1 HIKING EXPEDITION (CHE) undergoes sulfenylation in systemic tissues, which enhances its binding to the promoter of the SA-synthesis gene ISOCHORISMATE SYNTHASE1 (ICS1) and increases SA production. Furthermore, hydrogen peroxide (H2O2) produced through NADPH oxidases is the mobile signal that sulfenylates CHE in a concentration-dependent manner. Accumulation of SA and the previously reported signal molecules, such as N-hydroxypipecolic acid (NHP), then form a signal amplification loop to establish SAR.

Asunto(s)

Proteínas de Arabidopsis , Arabidopsis , Peróxido de Hidrógeno , Enfermedades de las Plantas , Ácido Salicílico , Factores de Transcripción , Arabidopsis/genética , Arabidopsis/microbiología , Arabidopsis/inmunología , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Peróxido de Hidrógeno/metabolismo , Ácido Salicílico/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Enfermedades de las Plantas/microbiología , Resistencia a la Enfermedad/genética , Regiones Promotoras Genéticas , Transferasas Intramoleculares/metabolismo , Transferasas Intramoleculares/genética , NADPH Oxidasas/metabolismo , NADPH Oxidasas/genética , Regulación de la Expresión Génica de las Plantas , Cisteína/metabolismo , Transducción de Señal , Pseudomonas syringae

RESUMEN

A colorimetric sensor for the rapid and sensitive detection of GSH was developed. The hydrothermal method was utilized to synthesize chitosan-stabilized gold nanoparticles (CS-AuNPs). The synthesized CS-AuNPs were characterized by UV-vis absorption spectroscopy, transmission electron microscopy (TEM), X-ray diffractograms (XRD), and Fourier transform infrared spectroscopy (FTIR). The CS-AuNPs are well-dispersed and possess a spherical shape with an average particle size of 10.05 ± 2.26 nm in aqueous solution. They show an intrinsic peroxidase-like activity, which could efficiently catalyze the decomposition of H2O2 to produce •OH radicals. These radicals then oxidized 3, 3´, 5, 5´-tetramethylbenzidine (TMB), resulting in the formation of the blue oxidized product oxTMB, observed a visible color change (from colorless to blue), and oxTMB had an obvious absorption peak at 652 nm. The presence of GSH could inhibit the peroxidase-like activity of CS-AuNPs, thereby reducing the formation of oxTMB. The solution's blue hue underwent a reduction in absorption intensity. Based on this fact, a novel and sensitive colorimetric sensor for detection of GSH was constructed. Under optimal conditions, the results of detection had an excellent linear relationship between the concentration of GSH and ∆A within the range 0.5 ~ 50.0 × 10-6 mol/L. The limit of detection (LOD) for GSH was 2.10 × 10-7 mol/L, which was much lower than those in most previous works. Furthermore, for detection in real human serum samples, the recoveries of GSH and the relative standard deviations (RSD) in the serum were in the range 98.40 ~ 103.32% and 1.85 ~ 3.54%, respectively. Thus, this visual colorimetric method has good precision and can be used for GSH detection in practical applications, promising in the fields of bioanalysis and illness diagnostics.

Asunto(s)

Quitosano , Colorimetría , Glutatión , Oro , Límite de Detección , Nanopartículas del Metal , Oro/química , Humanos , Colorimetría/métodos , Quitosano/química , Nanopartículas del Metal/química , Glutatión/sangre , Glutatión/química , Peróxido de Hidrógeno/química , Bencidinas/química , Peroxidasa/química

RESUMEN

Pathogen-host competition for manganese and intricate immunostimulatory pathways severely attenuates the efficacy of antibacterial immunotherapy against biofilm infections associated with orthopaedic implants. Herein, we introduce a spatiotemporal sono-metalloimmunotherapy (SMIT) strategy aimed at efficient biofilm ablation by custom design of ingenious biomimetic metal-organic framework (PCN-224)-coated MnO2-hydrangea nanoparticles (MnPM) as a metalloantibiotic. Upon reaching the acidic H2O2-enriched biofilm microenvironment, MnPM can convert abundant H2O2 into oxygen, which is conducive to significantly enhancing the efficacy of ultrasound (US)-triggered sonodynamic therapy (SDT), thereby exposing bacteria-associated antigens (BAAs). Moreover, MnPM disrupts bacterial homeostasis, further killing more bacteria. Then, the Mn ions released from the degraded MnO2 can recharge immune cells to enhance the cGAS-STING signaling pathway sensing of BAAs, further boosting the immune response and suppressing biofilm growth via biofilm-specific T cell responses. Following US withdrawal, the sustained oxygenation promotes the survival and migration of fibroblasts, stimulates the expression of angiogenic growth factors and angiogenesis, and neutralizes excessive inflammation. Our findings highlight that MnPM may act as an immune costimulatory metalloantibiotic to regulate the cGAS-STING signaling pathway, presenting a promising alternative to antibiotics for orthopaedic biofilm infection treatment and pro-tissue repair.

Asunto(s)

Biopelículas , Compuestos de Manganeso , Óxidos , Oxígeno , Biopelículas/efectos de los fármacos , Animales , Ratones , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Oxígeno/metabolismo , Óxidos/farmacología , Óxidos/química , Antibacterianos/farmacología , Peróxido de Hidrógeno/metabolismo , Inmunoterapia/métodos , Humanos , Terapia por Ultrasonido/métodos , Nanopartículas/química , Transducción de Señal/efectos de los fármacos , Antígenos Bacterianos/inmunología , Staphylococcus aureus/efectos de los fármacos , Femenino

RESUMEN

Based on the peroxidase activity of Cu-hemin metal-organic framework (Cu-hemin MOF) nanozyme, a colorimetric enzyme-linked immunosensor was developed for the detection of furazolidone (FZD). Cu-hemin MOF is a bimetallic nanozyme that exhibited a stronger catalytic effect compared with single-metal organic framework nanoenzymes. Cu-hemin-MOF catalyzes hydrogen peroxide (H2O2) to produce hydroxyl radicals (•OH), which oxidizes the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (oxTMB). The absorbance change is at 650 nm. The content of AOZ in animal food can be quickly and accurately determined by changes in absorbance. The linear range of the colorimetric biosensor for detecting FZD was 0.01 ~ 62.52 ng/mL, and the limit of detection was as low as 0.01 ng/mL. The recovery of spikes samples was in the range 94.2-108.0 % and reproducibility was less than 4.8%. In addition, the cross-reaction rate was less than 0.1% when detecting other metabolites except AOZ, indicating that the sensor has good applicability and specificity. This study not only provides a better understanding of the relationship between the dispersion of nanoenzymes and enzyme-like activity but also offers a general method for detecting antibiotics using the nanoenzyme colorimetric method.

Asunto(s)

Colorimetría , Cobre , Furazolidona , Hierro , Límite de Detección , Estructuras Metalorgánicas , Colorimetría/métodos , Cobre/química , Furazolidona/análisis , Furazolidona/química , Estructuras Metalorgánicas/química , Hierro/química , Bencidinas/química , Peróxido de Hidrógeno/química , Animales , Técnicas Biosensibles/métodos , Inmunoensayo/métodos , Catálisis

RESUMEN

BACKGROUND: Breast cancer, with its high morbidity and mortality rates, is a significant global health burden. Traditional treatments-surgery, chemotherapy, and radiotherapy-are widely used but come with drawbacks such as recurrence, metastasis, and significant side effects, including damage to healthy tissues. To address these limitations, new therapeutic strategies are being developed. Peroxidases (POD) can catalyze excess H2O2 in the tumor microenvironment to generate reactive oxygen species (ROS), which induce cancer cell apoptosis by disrupting redox homeostasis and modulating apoptosis-related proteins. However, natural enzymes face challenges like poor stability, high cost, and sensitivity to environmental conditions, limiting their application in breast cancer treatment. Nanozymes, nanomaterials with enzyme-like activity, offer a promising alternative by overcoming these limitations. METHODS: In this study, we successfully prepared Au@Pd nanozymes with peroxidase activity by depositing metallic Pd on Au nanoparticles (Au NPs) synthesized using a trisodium citrate reduction method and ascorbic acid reduction. The in vitro validation was conducted through a series of experiments, including ROS detection, flow cytometry, CCK-8 assay, DNA damage assessment, live/dead cell staining, Western blot (WB), and qPCR. Tumor treatment was performed via tail vein injection of the drug, followed by HE staining of the treated tissues and biochemical analysis of the blood. RESULTS: Au@Pd nanozymes can effectively accumulate at the tumor site through the EPR effect and exert peroxidase-like activity, catalyzing the excess H2O2 in the tumor microenvironment to produce ROS. This triggers apoptosis pathways and DNA damage, leading to the downregulation of the anti-apoptotic protein Bcl-2, upregulation of the pro-apoptotic protein Bax, and induction of apoptosis-related genes, demonstrating strong anti-tumor effects. CONCLUSIONS: This study developed an efficient nanozyme-mediated catalytic therapy strategy targeting the tumor microenvironment for the treatment of breast cancer cells.

Asunto(s)

Apoptosis , Oro , Nanopartículas del Metal , Paladio , Microambiente Tumoral , Microambiente Tumoral/efectos de los fármacos , Oro/química , Humanos , Catálisis , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Femenino , Paladio/uso terapéutico , Paladio/química , Paladio/farmacología , Animales , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Peróxido de Hidrógeno/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Ratones Desnudos

RESUMEN

Cellular oxidative stress mediated by intrinsic and/or extrinsic reactive oxygen species (ROS) is associated with disease pathogenesis. Oxidative DNA damage can naturally be substituted by mitochondrial DNA (mtDNA), leading to base lesion/strand break formation, copy number changes, and mutations. In this study, we devised a single test for the sensitive quantification of acute mtDNA damage, repair, and copy number changes using supercoiling-sensitive quantitative PCR (ss-qPCR) and examined how oxidative stress-related mtDNA damage responses occur in oral cancer cells. We observed that exogenous hydrogen peroxide (H2O2) induced dynamic mtDNA damage responses, as reflected by early structural DNA damage, followed by DNA repair if damage did not exceed a particular threshold. However, high oxidative stress levels induced persistent mtDNA damage and caused a 5-30-fold depletion in mtDNA copy numbers over late responses. This dramatic depletion was associated with significant growth arrest and apoptosis, suggesting persistent functional consequences. Moreover, oral cancer cells responded differentially to oxidative injury when compared with normal cells, and different ROS species triggered different biological consequences under stress conditions. In conclusion, we developed a new method for the sensitive detection of mtDNA damage and copy number changes, with exogenous H2O2 inducing dynamic mtDNA damage responses associated with functional changes in stressed cancer cells. Finally, our method can help characterize oxidative DNA damage in cancer and other human diseases.

Asunto(s)

Daño del ADN , ADN Mitocondrial , Peróxido de Hidrógeno , Neoplasias de la Boca , Estrés Oxidativo , Especies Reactivas de Oxígeno , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Estrés Oxidativo/efectos de los fármacos , Humanos , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Peróxido de Hidrógeno/farmacología , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Reparación del ADN , Apoptosis/efectos de los fármacos , Variaciones en el Número de Copia de ADN

RESUMEN

The key to heterogeneous photo-Fenton technology lies in the efficient generation of hydrogen peroxide (H2O2). Herein, a newly-designed ZnO/ZnIn2S4 composite with heterostructure is synthesized. Benefiting from the formation of built-in electric field, the recombination of photoinduced electrons and holes is suppressed and interfacial charge transfer resistance is reduced. Importantly, the embedding of ZnO in ZnIn2S4 can improve the hydrophobicity and create microscopic three-phase interface, thereby boosting the capture capability for O2 and providing the convenience for the occurrence of O2 reduction reaction. More interestingly, the existence of ZnIn2S4 in the ZnO/ZnIn2S4 composite can reduce the Gibbs free energy (ΔG) of key intermediate (OOH*) formation, which will accelerate the generation of H2O2. As a result, the ZnO/ZnIn2S4 composite displays excellent performance in photocatalytic H2O2 production, and the highest yield was about 897.6 µmol/g/h within 60 min under visible light irradiation. The transfer of photoinduced carriers follows the S-scheme type mechanism. The photogenerated holes can be captured by drug residues (i.e., diclofenac sodium) to accelerate H2O2 production, while generated H2O2 can combine with Fe2+ to construct photo-Fenton system for achieving the advanced degradation of diclofenac sodium, which was mainly related to the formation of OH•. Furthermore, generated H2O2 can be applied for performing the inactivation of pathogenic bacteria. In short, current work will provide a valuable reference for future research.

Asunto(s)

Restauración y Remediación Ambiental , Peróxido de Hidrógeno , Óxido de Zinc , Peróxido de Hidrógeno/química , Óxido de Zinc/química , Restauración y Remediación Ambiental/métodos , Catálisis , Adsorción , Oxígeno/química

RESUMEN

The aqueous FeIV-oxo complex and FeIII-peroxy complex (e.g., ligand-assisted or interfacial FeIII-hydroperoxo intermediates) have been recognized as crucial reactive intermediates for decontamination in iron-based Fenton-like processes. Intermediates with terminal oxo ligands can undergo the oxygen atom exchange process with water molecules, whereas peroxides are unable to induce such exchanges. Therefore, these distinct metal-oxygen complexes can be distinguished based on the above feature. In this study, we identified previously unknown intermediates with a peroxy moiety and cobalt center that were generated during peroxymonosulfate (PMS) activation via aqueous CoII ions under acidic conditions. Results of theoretical calculations and tip-enhanced Raman spectroscopy revealed that the CoII ion tended to coordinate with the PMS anion to form a bidentate complex with a tetrahedral structure. These reactive cobalt intermediates were collectively named the CoII-PMS* complex. Depending on the inherent characteristics of the target contaminants, the CoII-PMS* complex can directly oxidize organic compounds or trigger PMS disproportionation to release hydroxyl radicals and sulfate radicals for collaborative decontamination. This work provides a comparative study between iron- and cobalt-based Fenton-like processes and proposes novel insights from the standpoint of diverse metal-oxygen complexes.

Asunto(s)

Cobalto , Hierro , Oxígeno , Cobalto/química , Hierro/química , Oxígeno/química , Peróxido de Hidrógeno/química , Oxidación-Reducción , Peróxidos/química