Amount Of Reactive Oxygen Species Research Articles

Physical Activity Regulates and Mediates the Signaling Pathway and Pathophysiological Mechanisms of the Neuroinflammation and Neurodegenerative

Context: The correlation between neuroinflammation and neurodegenerative disorders has been extensively documented. Elevated levels of inflammatory cytokines in the bloodstream have been demonstrated to impair memory function and heighten susceptibility to neurodegenerative disorders. Furthermore, elevated quantities of reactive oxygen species (ROS) in the body, known as oxidative stress, exacerbate neurodegenerative illnesses and negatively affect learning and memory. Neuroprotection prevents neuronal cell death by intervening and blocking the pathogenetic process that leads to cellular malfunction and death. Methods: We evaluated several studies in the WEB of SCIENCE, SCOPUS, and PubMed. Furthermore, we identified the central genes and signaling pathways associated with neurogenesis, the neural system, and neuroplasticity through data mining, a literature review of artificial intelligence, and an in-silico study. Results: Physical exercise (PE) benefits various physiological systems, including the central nervous system. The beneficial impacts of physical activity on cognitive performance, neural well-being, and safeguarding neurons against different brain injuries are extensively documented. Furthermore, research has demonstrated that PE is a powerful non-pharmacological intervention that enhances cognitive function, including learning and memory, while decreasing the likelihood of developing neurodegenerative disorders. Additionally, engaging in moderate physical activity that does not result in extreme fatigue has a beneficial impact on reducing inflammation and promoting antioxidant effects. According to the hormesis theory, physical inactivity and extreme overtraining can decrease physiological function. Conclusions: In summary, a combination of moderate aerobic exercise, HIIT, and resistance training, performed at appropriate intensities, is most beneficial for neuroprotection and cognitive health. Regular engagement in these activities can help mitigate the risk of neurodegenerative diseases and enhance overall brain function.

Investigating antioxidant effects of hamamelitannin-conjugated zinc oxide nanoparticles on oxidative stress-Induced neurotoxicity in zebrafish larvae model.

An excessive amount of reactive oxygen species triggers oxidative stress, leading to an imbalance in cellular homeostasis. Antioxidant therapy is an effective tool for lowering the oxidative stress and associated ailments. Recently, green nano-based drug formulations have demonstrated promising antioxidant activity and neutralizing oxidative stress. In this study, a tannin molecule Hamamelitannin (HAM), was utilized to synthesize zinc oxide nanoparticles HAM-ZnO NPs, to mitigate oxidative stress and associated ailments . The HAM-ZnO NPs were synthesized and characterized by XRD, SEM, and FTIR. The antioxidant potentials of HAM-ZnO NPs were analyzed by in vitro antioxidant assays. Zebrafish embryos and larvae were used as in-vivo models to assess the toxicity and antioxidant protective mechanism. Hydrogen peroxide (1mM) was employed to induce oxidative stress and treated with HAM-ZnO NPs to study the cognitive impairment and antioxidant enzyme levels. Levels of reactive oxygen species and cell death due to oxidative stress induction were studied by 2',7'-dichlorodihydrofluorescein diacetate and Acridine orange staining methods. Additionally, expression of Antioxidant genes such as SOD, CAT, GPx, and GSR were studied. . HAM-ZnO NPs exhibited a spherical morphology and size ranges between 48 and 53nm. In vitro antioxidant studies revealed the antioxidant properties of HAM-ZnO NPs. Furthermore, in vivo studies indicated that HAM-ZnO NPs don't possess any cytotoxic effects in zebrafish larvae at concentrations between (5-25µg/ml), The study also observed that HAM-ZnO NPs significantly reduced Hydrogen Peroxide-induced stress and increased antioxidant activity in zebrafish larvae. Also, the antioxidant gene expression was upregulated in the HAM-ZnO NPs zebrafish larvae. Findings in this study showed that HAM-ZnO NPs might be a potential intervention for diseases linked to oxidative stress.

Environmentally Persistent Free Radicals stimulate CYP2E1-mediated generation of reactive oxygen species at the expense of substrate metabolism.

Environmentally persistent free radicals (EPFRs) are a recently recognized component of particulate matter that cause respiratory and cardiovascular toxicity. The mechanism of EPFR toxicity appears to be related to their ability to generate reactive oxygen species (ROS), causing oxidative damage. EPFRs were shown to affect P450 function, inducing the expression of some forms through the Ah receptor. However, another characteristic of EPFRs lies in their ability to inhibit P450 activities. CYP2E1 is one of the P450s that is inhibited by EPFR (MCP230) exposure. As CYP2E1 is also known to generate ROS, it is important to understand the ability of EPFRs to influence the function of this enzyme and to identify the mechanisms involved. CYP2E1 was shown to be inhibited by EPFRs, and to a lesser extent by non-EPFR particles. As EPFR-mediated inhibition was more robust at subsaturating NADPH-cytochrome P450 reductase (POR) concentrations, disruption of POR·CYP2E1 complex formation and electron transfer were examined. Surprisingly, neither complex formation nor electron transfer between POR and CYP2E1 were inhibited by EPFRs. Examination of ROS production showed that MCP230 generated a greater amount of ROS than the non-EPFR CuO-Si. When a POR/CYP2E1-containing reconstituted system was added to the pollutant-particle systems there was a synergistic stimulation of ROS production. The results indicate that EPFRs cause inhibition of CYP2E1-mediated substrate metabolism, yet do not alter electron transfer and actually stimulate ROS generation. Taken together, the results are consistent with EPFRs affecting CYP2E1 function by inhibiting substrate metabolism and increasing the generation of ROS. Significance Statement Environmentally persistent free radicals affect CYP2E1 function by inhibition of monooxygenase activity. This inhibition is not due to disruption of the POR·CYP2E1 complex or inhibition of electron transfer, but due to uncoupling of NADPH and oxygen consumption from substrate metabolism to the generation of ROS. These results show that EPFRs block the metabolism of foreign compounds, and also synergistically stimulate the formation of reactive oxygen species that lead to oxidative damage within the organism.

A highly permeable nanoplatform based on functionalized carbon dots for synergistic reactive oxygen/nitrogen species tumor therapy

Reactive oxygen species (ROS)-based antitumor strategies, particularly chemodynamic therapy, have garnered considerable attention. However, challenges such as difficulties in achieving deep penetration, relatively low H2O2 levels in the tumor microenvironment, the requirement for low pH by the Fenton reaction, and their short lifespan have impeded satisfactory therapeutic outcomes. Hence, we have developed a nanoplatform with enhanced permeability that not only generates significant amounts of ROS but also converts them into longer-lasting reactive nitrogen species (RNS), thereby improving tumor therapy efficacy. In our study, carbon dots were functionalized by doping with gold atoms and grafting nitrosoglutathione (GSNO) to form ACN, which exhibits glucose oxidase-like properties and enables laser-responsive NO release. ACN and indocyanine green (ICG) were then loaded onto MnO2 nanoflowers to form MnO2@AI. Upon arrival at the tumor site, MnO2 reacts with H2O2 and GSH, leading to its degradation and the subsequent release of ACN, which is characterized by three permeation-promoting properties: ultra-small size, positive charge, and NO content. In addition, ACN promotes H2O2 production through glucose metabolism and reduces pH, both of which enhance the Fenton-like reaction of MnO2, thereby amplifying ROS generation. The ICG in MnO2@AI enhances its photothermal properties, leading to the responsive release of NO from GSNO grafted onto ACN, which then reacts with the increased ROS to generate more toxic RNS. Collectively, the approach described herein offers substantial potential for advancing the treatment of malignant tumors.

Stratified nanoflower bimetallic cobalt/iron alloy derived from CoFe-MOFs as efficient peroxymonosulfate activator for antibiotics degradation: Performance, mechanism, and toxicity

Co-based metal-organic framework (Co-MOFs) derivative has gained wide attention in the field of advanced oxidative processes (AOPs). However, the degradation efficiency of single cobalt element remains suboptimal and its activation mechanism still needs to be further explored. In this study, stratified nanoflower bimetallic cobalt/iron alloys (CoFe-NC), derived from cobalt/iron bimetallic-organic frameworks (CoFe-MOFs), was synthesized via self-assembly at room temperature, hydrothermal synthesis and high-temperature carbonization processes and their performance as efficient activators of peroxymonosulfate (PMS) for the degradation of antibiotics was evaluated (removal efficiency of 100 % within 40 min, k=0.0951 min−1). The excellent degradation property benefit by specific nano-flowers structure with high specific surface area (424.67 m2/g), the cycle between Co0→Co2+↔ Co3+ and Fe0→Fe2+↔Fe3+, synergistic effect of Co and Fe bimetals. Furthermore, the CoFe-NC/PMS system exhibits exceptionally high cyclic stability (over 85 % degradation efficiency after four times degradation), a wide range of pH (3−11) and resistance to background ion interference (Cl–, H2PO4–, NO3–, HCO3– and HA), and reduced toxicity of the degradation products. Degradation mechanistic studies demonstrated that the activation of PMS by CoFe-NC generated amounts of reactive oxygen species (ROS) (SO4•−, •OH, •O2− and 1O2). Additionally, high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis identified fifteen intermediate degradation products and three possible degradation pathways were proposed. The results highlight the potential of CoFe-NC as a catalyst for antibiotic removal, providing insights into the optimization of bimetallic-organic framework for environmental applications.

Motor-Cargo Structured Nanotractors for Augmented NIR Phototherapy via Gas-Boosted Tumor Penetration and Respiration-Impaired Mitochondrial Dysfunction.

Tumor microenvironment, characterized by dense extracellular matrix and severe hypoxia, has caused pronounced resistance to photodynamic therapy (PDT). Herein, it has designed an artificial nitric oxide (NO) nanotractor with a unique "motor-cargo" structure, where a photoswitching upconversion nanoparticle (UCNP) core serves as the optical engine to harvest NIR light and asymmetrically coated mesoporous silica (SiO2) shell acts as a cargo unit to load nitric oxide (NO) fuel molecule (RBS, Roussin's black salt) and PDT photosensitizer (ZnPc, zinc phthalocyanine). Upon illumination by 980nm light, the UCNP emits blue light to excite RBS salt and release NO gas. On one hand, NO is used as the driving force to propel the particle with a high speed of ≈194µms-1 that generates significant rupture stress (over 0.95kPa) on cell membrane to promote cellular endocytosis and intratumoral penetration. On the other hand, NO enables to alleviate tumor hypoxia by inhibiting cellular respiration as an oxygen conserver. When the excitation is subsequently switched to 808nm light, the UCNP emits red light, triggering ZnPc to produce large amount of reactive oxygen species for PDT treatment. This study explores Janus-typed nanostructures for cell-particle interaction and gas-assisted phototherapy, opening avenues for versatile bioapplications.

Engineered microparticles modulate arginine metabolism to repolarize tumor-associated macrophages for refractory colorectal cancer treatment

BackgroundArginase is abundantly expressed in colorectal cancer and disrupts arginine metabolism, promoting the formation of an immunosuppressive tumor microenvironment. This significant factor contributes to the insensitivity of colorectal cancer to immunotherapy. Tumor-associated macrophages (TAMs) are major immune cells in this environment, and aberrant arginine metabolism in tumor tissues induces TAM polarization toward M2-like macrophages. The natural compound piceatannol 3ʹ-O-glucoside inhibits arginase activity and activates nitric oxide synthase, thereby reducing M2-like macrophages while promoting M1-like macrophage polarization.MethodsThe natural compounds piceatannol 3ʹ-O-glucoside and indocyanine green were encapsulated within microparticles derived from tumor cells, termed PG/ICG@MPs. The enhanced cancer therapeutic effect of PG/ICG@MP was assessed both in vitro and in vivo.ResultsPG/ICG@MP precisely targets the tumor site, with piceatannol 3ʹ-O-glucoside concurrently inhibiting arginase activity and activating nitric oxide synthase. This process promotes increased endogenous nitric oxide production through arginine metabolism. The combined actions of nitric oxide and piceatannol 3ʹ-O-glucoside facilitate the repolarization of tumor-associated macrophages toward the M1 phenotype. Furthermore, the increase in endogenous nitric oxide levels, in conjunction with the photodynamic effect induced by indocyanine green, increases the quantity of reactive oxygen species. This dual effect not only enhances tumor immunity but also exerts remarkable inhibitory effects on tumors.ConclusionOur research results demonstrate the excellent tumor-targeting effect of PG/ICG@MPs. By modulating arginine metabolism to improve the tumor immune microenvironment, we provide an effective approach with clinical translational significance for combined cancer therapy.

Transport of microplastics treated with dielectric barrier discharge (DBD) plasma in saturated porous media

The performance of discharge plasma in treating organic pollutants and micro-organisms in water is impressive. When discharge plasma is used to treat polluted water containing organic pollutants and microorganisms, the presence of a certain amount of microplastics (MPs) in the water is unavoidable due to the complexity of the components contained in the water and the prevalence of MPs. MPs, as one of the pollutants that are difficult to be degraded by discharge plasma, undergo physical and chemical changes that increase their risk in the environment after treatment. Therefore, it is necessary to understand the fate of MPs after being treated with discharge plasma. In this study, the surface morphology of plastics before and after discharge plasma treatment was observed by scanning electron microscopy (SEM). The plastics after discharge plasma treatment were characterized by Fourier transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS) to determine the changes in oxygen-containing functional groups on the surface. The recovery of microplastics (MPs) in saturated porous media under different physicochemical and plasma oxidation conditions was investigated by column experiments. It has been shown that MPs exhibit increased recovery under conditions of increased flow rate and pH. A decrease in recovery was observed at elevated ionic strength and co-existing cation valence. High voltages and low air flow rates increase the oxidation of MPs by increasing the thermal effects of the dielectric barrier discharge (DBD) plasma system, the amount of reactive oxygen species (ROS) and the intensity of ultraviolet ray (UV) irradiation. The mobility of MPs is enhanced by a combination of these factors. The advection–dispersion equation (ADE) fits the transport data of MPs well. The interaction energy between quartz sand and MPs was calculated using the Derjaguin–Landau–Verwey–Overbeek (DLVO) theory. This study provides a new perspective on the potential risks of discharge plasma in water treatment.

APEX1 in intestinal epithelium triggers neutrophil infiltration and intestinal barrier damage in ulcerative colitis

Ulcerative colitis (UC) can lead to the generation of large amounts of reactive oxygen species and DNA damage. DNA repair caused by base excision repair (BER) enzymes is an important mechanism for maintaining genomic integrity. However, the specific relationship between the function of BER enzymes and UC remains unclear. To address this, we conducted a study on non-cancerous colon tissue from patients with UC, focusing on the role of apurinic/apyrimidinic endonuclease 1 (APEX1) in BER to explore its significance in the progression of UC. Our research found that the expression of APEX1 in epithelium cells was significantly correlated to the severity of inflammatory bowel disease (IBD) and the infiltration and function of neutrophils in human UC and mouse models, particularly in relation to neutrophil extracellular traps (NETs) and the degranulation processes. APEX1 deficiency resulted in decreased production of the chemokines CXCL1 by the NF-κB pathway in epithelium cells, leading to reduced accumulation and activation of neutrophils associated with colitis in colon tissue, as well as decreased levels of IL-1β. Furthermore, APEX1 deficiency reduced symptoms of colitis by decreasing epithelial cell apoptosis and altering the gut microbiome. Studies related to the redox activity of APEX1 have shown that the combination of the redox inhibitor E3330 with 5-aminosalicylic acid (5-ASA) can effectively alleviate colitis, indicating that APEX1 has promising prospects for clinical treatment of IBD. APEX1 is required for interactions between neutrophil and intestinal epithelial cells. This study provided a mechanism demonstrating that APEX1 protein triggered the risk of UC by promoting neutrophil infiltration and compromising intestinal epithelial barrier function.

Simultaneous production of singlet oxygen and superoxide anion by thiocarbonyl coumarin for photodynamic therapy

Photodynamic therapy (PDT) is a medical treatment that kills target cells through reactive oxygen species (ROS) generated by photosensitizers (PS) and surrounding oxygen under the stimulus of light. Despite of its popularity in cancer treatment, PDT relys on oxygen and therefore suffers from long response time and low efficiency under low-oxygen situations such as tumor hypoxia. Herein, to improve the usage of oxygen and increase ROS yield, we synthesized six potential PSs termed DC-O, DC-S, DC-BrO, DC-BrS, DC-IO, and DC-IS, by modifying coumarins with thiocarbonyl and bromine/iodine. We found that the thiocarbonyl group induces a significant bathochromic shift of the absorption spectra. In addition, the ROS production was significantly improved, likely because these PSs can simultaneously generate singlet oxygen (1O2) and superoxide anions (O2•−) through different pathways. Among these compounds, DC-BrS produces largest amount of ROS and exhibits strongest cytotoxicity towards cells, the survival rate of B16-F10 cells incubated with DC-BrS was only 20.7 % after irradiation at 460 nm for 10 min, indicating DC-BrS as a strong candidate for photodynamic therapy. Most importantly, this work provides an important direction for the design of PSs in the future.

The Potential Role of Reactive Oxygen Species Produced by Low-Density Neutrophils in Periodontitis.

Neutrophils own an arsenal of dischargeable chemicals that enable them to handle bacterial challenges, manipulating innate immune response and actual participation in acquired immunity. The reactive oxygen species (ROS) are one of the most important chemicals that neutrophils discharge to eradicate pathogens. Despite their beneficial role, the ROS were strongly correlated to periodontal tissue destruction. Lowdensity neutrophils (LDN) have been recognized for producing enhanced quantities of ROS. However, the potential role of ROS produced by LDN in periodontitis is unknown. The aim of the study was to investigate the impact of ROS produced by LDN in periodontal diseases. Venous blood and periodontal parameters were obtained from 100 systemically healthy subjects divided into 40 participants with healthy periodontium in the control group and 60 with unstable periodontitis in the study group. Flow cytometry was used to measure the production of ROS by LDN in both groups. The data were analyzed for normal distribution using the Shapiro-Wilk test at p < 0.05, Spearman's correlations, and Mann-Whitney U test. Statistical analysis was performed in SPSS v25. No difference between the groups had been obtained in ROS production by LDN. However, a significant positive correlation existed between ROS and clinical attachment loss in periodontitis. LDN exhibits the same ROS generation capacity in the control and periodontitis groups.

Effects of Pressure, Hypoxia, and Hyperoxia on Neutrophil Granulocytes

Background: The application of normo- and hyperbaric O2 is a common therapy option in various disease patterns. Thereby, the applied O2 affects the whole body, including the blood and its components. This study investigates influences of pressure and oxygen fraction on human blood plasma, nutrient media, and the functions of neutrophil granulocytes (PMNs). Methods: Neutrophil migration, reactive oxygen species (ROS) production, and NETosis were examined by live cell imaging. The treatment of various matrices (Roswell Park Memorial Institute 1640 medium, Dulbecco’s Modified Eagle’s Medium, H2O, human plasma, and isolated PMNs) with hyperbaric oxygen (HBO) was performed. In addition, the expression of different neutrophil surface epitopes (CD11b, CD62L, CD66b) and the oxidative burst were investigated by flow cytometry (FACS). The application of cold atmospheric plasma (CAP) to normoxic and normobaric culture media served as a positive control. Soluble reaction products such as H2O2, reactive nitrogen species (RNS: NO2− and NO3−), and ROS-dependent dihydrorhodamine oxidation were quantified by fluoro- and colorimetric assay kits. Results: Under normobaric normoxia, PMNs migrate slower and shorter in comparison with normobaric hyper- or hypoxic conditions and hyperbaric hyperoxia. The pressure component has less effect on the migration behavior of PMNs than the O2 concentration. Individual PMN cells produce prolonged ROS at normoxic conditions. PMNs showed increased expression of CD11b in normobaric normoxia, lower expression of CD62L in normobaric normoxia, and lower expression of CD66b after HBO and CAP treatment. Treatment with CAP increased the amount of ROS and RNS in common culture media. Conclusions: Hyperbaric and normobaric O2 influences neutrophil functionality and surface epitopes in a measurable way, which may have an impact on disorders with neutrophil involvement. In the context of hyperbaric experiments, especially high amounts of H2O2 in RPMI after hyperbaric oxygen should be taken into account. Therefore, our data support a critical indication for the use of normobaric and hyperbaric oxygen and conscientious and careful handling of oxygen in everyday clinical practice.

PH and ROS Dual-Responsive Autocatalytic Release System Potentiates Immunotherapy of Colorectal Cancer.

The immunosuppressive microenvironment severely limits the responsiveness of colorectal cancer (CRC) to immunotherapy. Herein, a pH and reactive oxygen species (ROS) dual-responsive autocatalytic release system (TPDM/PGA) is constructed to reverse the immunosuppressive microenvironment and potentiate CRC immunotherapy. Dihydroartemisinin (DHA) and mitoxantrone (MTO) are conjugated to ROS-responsive polyethylenimine (TP) via a ROS-cleavable linker, respectively, and then coated with polyglutamic acid (PGA) to endow pH and ROS dual-responsiveness. The dissociation of PGA within the acidic TME facilitates its deep penetration and cell internalization, while the intracellular released DHA and MTO in response to high levels of H2O2 further produced a large amount of ROS, forming positive feedback to accelerate drug release and exacerbate oxidative stress. TPDM/PGA collaboratively reversed the immunosuppressive microenvironment and induced a strong anti-tumor immune response when combined with anti-PD-L1 antibody, significantly inhibiting tumor growth and prolonging the survival time of CT26 and MC38 tumor-bearing mice. The excellent therapeutic effect, together with the good tolerance, make TPDM/PGA a promising candidate for enhanced immunotherapy of colorectal cancer.

Transcription factor gene TaWRKY76 confers plants improved drought and salt tolerance through modulating stress defensive-associated processes in Triticum aestivum L.

WRKY transcription factor (TF) family acts as essential regulators in plant growth and abiotic stress responses. This study reported the function of TaWRKY76, a member of WRKY TF family in Triticum aestivum L., in regulating plant osmotic stress tolerance. TaWRKY76 transcripts were significantly upregulated upon drought and salt signaling, with dose extent- and stress temporal-dependent manners. Plant GUS activity assays suggested that stress responsive cis-acting elements, such as DRE and ABRE, exert essential roles in defining gene transcription under osmotic stress conditions. The TaWRKY76 protein targeted onto nucleus and possessed ability interacting with TaMYC2, a MYC TF member of wheat. TaWRKY76 and TaMYC2 positively regulated plant drought and salt adaptation by modulating osmotic stress-related physiological indices, including osmolyte contents, stomata movement, root morphology, and reactive oxygen species (ROS) homeostasis. Yeast one-hybrid assay indicated the binding ability of TaWRKY76 with promoters of TaDREB1;1, TaNCEB3, and TaCOR15;4. ChIP-PCR analysis confirmed that the osmotic stress genes are transcriptionally regulated by TaWRKY76. Moreover, the transgenic lines with knockdown of these stress-response genes displayed lowered plant biomass together with worsened root growth traits, decreased proline contents, and elevated ROS amounts. These results suggested that these stress defensive genes contributed to TaWRKY76-modulated osmotic stress tolerance. Highly positive correlations were observed between yield and the transcripts of TaWRKY76 in a wheat variety panel under field drought condition. A major haplotype TaWRKY76 Hap1 conferred improved drought tolerance. Our results suggested that TaWRKY76 is essential in plant drought and salt adaptation and a valuable target for molecular breeding stress-tolerant cultivars in Triticum aestivum L..

A Wurster-Type Covalent Organic Framework with Internal Electron Transfer-Enhanced Catalytic Capacity for Tumor Therapy.

The low immunogenicity of tumors, along with the abnormal structural and biochemical barriers of tumor-associated vasculature, impedes the infiltration and function of effector T cells at the tumor site, severely inhibiting the efficacy of antitumor immunotherapy. In this study, a cobaloxime catalyst and STING agonist (MSA-2)-coloaded Wurster-type covalent organic framework (Co-TB COF-M) with internal electron transfer-enhanced catalytic capacity was developed as a COF-based immune activator. The covalently anchored cobaloxime adjusts the energy band structure of TB COF and provides it with good substrate adsorption sites, enabling it to act as an electron transmission bridge between the COF and substrate in proton reduction catalytic reactions. This property significantly enhances the sonodynamic catalytic performance. Under sono-irradiation, Co-TB COF-M can produce a substantial amount of reactive oxygen species (ROS) to induce Gasdermin D-mediated pro-inflammatory pyroptosis, thereby effectively enhancing the immunogenicity of tumors. Furthermore, MSA-2 is specifically released in response to ROS at the tumor site, minimizing the off-target side effects. More importantly, Co-TB COF-induced STING activation normalizes tumor vasculature and increases the expression of endothelial T cell adhesion molecules, which greatly enhance the infiltration and function of effector T cells. Thus, Co-TB COF-M as an immune activator could remold the tumor microenvironment, leading to increased infiltration and an improved function of T cells for immunotherapy.

Fluorinated triphenylamine phthalocyanine @ silica-coated gold nanorods: A photoactivated lysosome escape and targeting mitochondria two-photon probe for imaging-guided photothermal synergistic photodynamic therapy in cancer cells

The timely evasion of nanomedicines from lysosomes is essential to avert premature degradation under the acidic and hydrolytic conditions characteristic of these cellular compartments. However, the development of effective strategies has been hindered by the complexity of design material and the scarcity of practical methods. In this study, we have synthesized a novel nanoparticle, designated as TPA-BPAF-SiPc@AuNR@SiO2. This nanoparticle was prepared by encapsulating near-infrared fluorinated triphenylamine-substituted silicon phthalocyanines (TPA-BPAF-SiPc) within mesoporous silica-coated gold nanorods (AuNR@SiO2). TPA-BPAF-SiPc@AuNR@SiO2 functions as a dual-function two-photon probe, facilitating photoactivated lysosome escape and targeting mitochondria. The inherent aggregation-induced emission (AIE) two-photon fluorescence of TPA-BPAF-SiPc is notably bright when encapsulated in AuNR@SiO2 nanocarriers, a phenomenon not observed in polymer nanocarriers composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) or in THF/water mixtures. Upon irradiation, this nanoparticle autonomously escapes from lysosomes and selectively targets mitochondria, a process can be visually monitored in real-time through the two-photon AIE fluorescence of TPA-BPAF-SiPc. Moreover, upon activation, TPA-BPAF-SiPc@AuNR@SiO2 produces a substantial quantity of reactive oxygen species (ROS) and induces hyperthermia effects, showcasing its potential for effective photodynamic therapy (PDT) in conjunction with synergistic hyperthermia. Flow cytometry data corroborate the induction of tumor cell death through both necrosis and apoptosis pathways by TPA-BPAF-SiPc@AuNR@SiO2. This study underscores the potential of TPA-BPAF-SiPc@AuNR@SiO2 as a multifunctional probe capable of enabling lysosome escape, mitochondria targeting, and two-photon fluorescence imaging-guided photothermal synergistic photodynamic therapy, specifically tailored for the treatment of breast cancer.

Highly efficient and broad-spectrum antibacterial carbon dots combat antibiotic resistance

Bacterial infections have become a major global public health issue, particularly with the emergence of multidrug-resistant strains. Therefore, developing non-antibiotic antimicrobial agents is crucial for treating drug-resistant bacterial infections. Building on previous research into natural products as novel antibacterial agents, this study synthesized curcumin-derived carbon dots using curcumin and ethylenediamine as raw materials through a hydrothermal method. The resulting carbon dots not only improved the water solubility and stability of curcumin but also exhibited highly efficient broad-spectrum antibacterial activity. Detailed investigations into the antibacterial performance and mechanisms of the carbon dots were conducted through experiments such as minimum inhibitory concentration (MIC) determination, live/dead bacterial staining, morphological studies, nucleic acid concentration detection, and reactive oxygen species (ROS) detection. The results indicated that the carbon dots significantly damaged the structural integrity of bacteria and generated large amounts of ROS. They exhibited remarkable antibacterial effects against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and effectively inhibited drug-resistant MRSA. Their antibacterial efficacy was notably superior to that of broad-spectrum antibiotics such as chloramphenicol and Sulfadiazine. This study highlights the potential application of curcumin-derived carbon dots in combating bacterial infections and provides valuable insights for developing novel antibacterial agents derived from natural products.

Studies on the antifungal effects of Hinokitiol on Candida albicans: inhibition of germ tube formation and synergistic pharmacological effects of miconazole.

One of the goals of oral healthcare management is to manage dry mouth. Thus, moisturizers containing antimicrobial ingredients, such as hinokitiol (HT), are applied to the oral mucosa after oral care. In this study, we investigated the preventive effect of HT against the growth of Candida albicans (C. al) and its synergistic effect when combined with miconazole (MCZ), an oral treatment for candidiasis. As the concentration of HT increased, the length and percentage of germ tubes (GT) decreased. Larger inhibition circles were observed for MCZ concentrations of 2.0 and 4.0μg/disc compared to the HT medium without HT. The increased inhibitory effect was observed in both aerobic and anaerobic cultures. This suggests that the production of reactive oxygen species (ROS) by C. al cells increased with the combination of HT and MCZ. The length and percentage of GT increased, whereas the amount of ROS decreased when ROS scavengers were used in combination with the drug. HT led to morphological changes that inhibited the GT associated with pathogenic C. al, exhibited a complementary action against MCZ, and showed a possible association with hydrogen peroxide and superhydroxy anion radicals. These effects suggest that HT is a promising candidate for inhibiting C. al. In conclusion, HT demonstrated a prophylactic effect by inhibiting C. al and a synergistic effect with MCZ, a drug used to treat oral candidiasis. HT may also be useful for suppressing the onset and reducing the severity of oral candidiasis.

Protective effects of betanin, a novel acetylcholinesterase inhibitor, against H2O2-induced apoptosis in PC12 cells.

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. 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 (150µM) resulted in cell viability reduction and apoptosis induction while, pretreatment with the betanin (10, 20, and 50μM) and N-Acetyl-L-cysteine (NAC) (2.5 and 5mM) significantly increased the viability (P < 0.05, P < 0.01 and P < 0.001) and at 5-50μM betanin decreased ROS amount (P < 0.05, P < 0.01 and P < 0.001). Whereas, pretreatment with the betanin (10, 20, and 50μM) decreased AChE activity (P < 0.001), also at 20 and 50μM betanin reduced the release of LDH (P < 0.001), and at 10-50μM 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 10-20μM and 10-50μM respectively. Indeed, survivin (P < 0.001) increased after pretreatment of cells with betanin at 10-20μM. 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.

Antibacterial mechanism of water-soluble CeO2 nanoflowers and its product design in antibacterial application

Antibacterial surface coatings have attracted growing attention in the textile industry. In this study, water-soluble CeO2 nanoflowers were synthesized by a modified critical micelle antisolvent method, displaying the potential for mass production at a low cost. The structure and electronic states of CeO2 were investigated deeply. Moreover, the antibacterial mechanism of CeO2 was studied in depth. The results revealed that CeO2 nanoflowers with abundant oxygen vacancies can adsorb O2 and produce amounts of reactive oxygen species (ROS) by the electron transfer of Ce4+ and Ce3+. These compounds can destroy cell walls, resulting in the leakage of bacterial nucleic acids and proteins, leading to bacterial death. The CeO2 nanoflowers exhibited broad-spectrum antimicrobial properties and biological safety. The antibacterial cotton fabric was prepared by the impregnation method. Considering the material impregnation amounts and impregnation time, a new washing machine was designed to prepare the antibacterial fabric. In this work, fabrics were modified using CeO2 nanoflowers with a simple method suitable for mass production, showing great application potential in antimicrobial cotton fabric. In addition, in order to further expand the application field of CeO2 nanoflowers, antibacterial elevator button patches, antibacterial coatings and other products were designed.