Therapeutic Potential of Pentoxifylline in Paraquat-Induced Pulmonary Toxicity: Role of the Phosphodiesterase Enzymes.

Pentoxifylline (PTX), a non-selective phosphodiesterase inhibitor, has demonstrated protective effects against lung injury in animal models. Given the significance of pulmonary toxicity resulting from paraquat (PQ) exposure, the present investigation was designed to explore the impact of PTX on PQ-induced pulmonary oxidative impairment in male mice.Following preliminary studies, thirty-six mice were divided into six groups. Group 1 received normal saline, group 2 received a single dose of PQ (20 mg/kg; i.p.), and group 3 received PTX (100 mg/kg/day; i.p.). Additionally, treatment groups 4-6 were received various doses of PTX (25, 50, and 100 mg/kg/day; respectively) one hour after a single dose of PQ. After 72 hours, the animals were sacrificed, and lung tissue was collected.PQ administration caused a significant decrease in hematocrit and an increase in blood potassium levels. Moreover, a notable increase was found in the lipid peroxidation (LPO), nitric oxide (NO), and myeloperoxidase (MPO) levels, along with a notable decrease in total thiol (TTM) and total antioxidant capacity (TAC) contents, catalase (CAT) and superoxide dismutase (SOD) enzymes activity in lung tissue. PTX demonstrated the ability to improve hematocrit levels; enhance SOD activity and TTM content; and decrease MPO activity, LPO and NO levels in PQ-induced pulmonary toxicity. Furthermore, these findings were well-correlated with the observed lung histopathological changes.In conclusion, our results suggest that the high dose of PTX may ameliorate lung injury by improving the oxidant/antioxidant balance in animals exposed to PQ.

Multifunctional N, Fe-doped carbon dots with peroxidase-like activity for the determination of H2O2 and ascorbic acid and cell protection against oxidation.

Multifunctional N, Fe-doped carbon dots (N, Fe-CDs) were synthesized by the one-step hydrothermal method using ferric ammonium citrate and dicyandiamide as raw materials. The N, Fe-CDs exhibited peroxidase-like (POD) activity by catalyzing the oxidization of 3,3',5,5'-tetramethylbenzidine (TMB) to the green oxidation state ox-TMB in the presence of hydrogen peroxide (H2O2). Subsequently, based on the POD activity of N, Fe-CDs, an efficient and sensitive colorimetric method for the detection of H2O2 and ascorbic acid (AA) was established with a limit of detection of 0.40 µM and 2.05 µM. The proposed detection method has been successfully applied to detect AA in fruit juice, vitamin C tablets, and human serum samples and has exhibited excellent application prospects in biotechnology and food fields. Furthermore, N, Fe-CDs also showed a protective effect on the cell damage caused by H2O2 and could be used as an antioxidant agent.

Histopathological evaluation of the lungs in experimental autoimmune encephalomyelitis.

IMPORTANCE: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by inflammation within the central nervous system. However, inflammation in non-neuronal tissues, including the lungs, has not been fully evaluated. OBJECTIVE: This study evaluated the inflammatory response in lungs of EAE mice by immunohistochemistry and histochemistry. METHODS: Eight adult C57BL/6 mice were injected with myelin oligodendrocyte glycoprotein35-55 to induce the EAE. Lungs and spinal cords were sampled from the experimental mice at the time of sacrifice and used for the western blotting, histochemistry, and immunohistochemistry. RESULTS: Histopathological examination revealed inflammatory lesions in the lungs of EAE mice, characterized by infiltration of myeloperoxidase (MPO)- and galectin-3-positive cells, as determined by immunohistochemistry. Increased numbers of collagen fibers in the lungs of EAE mice were confirmed by histopathological analysis. Western blotting revealed significantly elevated level of osteopontin (OPN), cluster of differentiation 44 (CD44), MPO and galectin-3 in the lungs of EAE mice compared with normal controls (p < 0.05). Immunohistochemical analysis revealed both OPN and CD44 in ionized calcium-binding adapter molecule 1-positive macrophages within the lungs of EAE mice. CONCLUSIONS AND RELEVANCE: Taken together, these findings suggest that the increased OPN level in lungs of EAE mice led to inflammation; concurrent increases in proinflammatory factors (OPN and galectin-3) caused pulmonary impairment.

Synthesis and Characterization of Cross-Linked Aggregates of Peroxidase from Megathyrsus maximus (Guinea Grass) and Their Application for Indigo Carmine Decolorization.

We present the synthesis of a cross-linking enzyme aggregate (CLEAS) of a peroxidase from Megathyrsus maximus (Guinea Grass) (GGP). The biocatalyst was produced using 50%v/v ethanol and 0.88%w/v glutaraldehyde for 1 h under stirring. The immobilization yield was 93.74% and the specific activity was 36.75 U mg-1. The biocatalyst surpassed by 61% the free enzyme activity at the optimal pH value (pH 6 for both preparations), becoming this increase in activity almost 10-fold at pH 9. GGP-CLEAS exhibited a higher thermal stability (2-4 folds) and was more stable towards hydrogen peroxide than the free enzyme (2-3 folds). GGP-CLEAS removes over 80% of 0.05 mM indigo carmine at pH 5, in the presence of 0.55 mM H2O2 after 60 min of reaction, a much higher value than when using the free enzyme. The operational stability showed a decrease of enzyme activity (over 60% in 4 cycles), very likely related to suicide inhibition.

The Role of CCL Chemokines in Experimental Staphylococcus aureus Endophthalmitis.

Purpose: To test the hypothesis that (C-C motif) ligand 2 (CCL2) and CCL3 impact retinal function decline and inflammation during Staphylococcus aureus endophthalmitis. Methods: Experimental endophthalmitis was initiated by intravitreal injection of 5000 colony-forming units of S. aureus into the eyes of C57BL/6J, CCL2-/-, or CCL3-/- mice. At 12 and 24 hours post-infection, retinal function, bacterial load, and myeloperoxidase levels were quantified. Results: During S. aureus endophthalmitis, we observed a significant improvement in retinal function in CCL2-/- mice relative to C57BL/6J mice at 12 hours but not at 24 hours. In CCL3-/- mice, retinal function was significantly improved relative to C57BL/6J mice at 12 and 24 hours. The absence of CCL2 did not alter intraocular S. aureus intraocular concentrations. However, CCL3-/- mice had significantly lower intraocular S. aureus at 12 hours but not at 24 hours. No difference in myeloperoxidase levels was observed between C57BL/6J and CCL2-/- mice at 12 hours. CCL3-/- mice had almost no myeloperoxidase at 12 hours. At 24 hours, increased myeloperoxidase was observed in CCL2-/- and CCL3-/- mice relative to C57BL/6J mice. Conclusions: Although the absence of CCL2 resulted in improved retinal function retention at 12 hours, CCL3 deficiency resulted in improved retinal function at 12 and 24 hours. CCL3 deficiency, but not CCL2 deficiency, resulted in almost no inflammation at 12 hours. However, at 24 hours, the absence of CCL2 or CCL3 resulted in significantly increased inflammation. These results suggest that, although both CCL2 and CCL3 impact intraocular infection outcomes, CCL3 may have a more significant impact in S. aureus endophthalmitis.

Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression in myelodysplastic neoplasms (MPO-MDS-Valid): protocol for a multicentre diagnostic accuracy study.

INTRODUCTION: Many patients referred for suspicion of myelodysplastic neoplasm (MDS) are subjected to unnecessary discomfort from bone marrow aspiration, due to the low disease prevalence in this population. Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression could rule out MDS with sensitivity and negative predictive value estimates close to 100%, ultimately obviating the need for bone marrow aspiration in up to 35% of patients. However, the generalisability of these findings is uncertain due to the limited sample size, the enrolment of patients at a single study site, and the reliability issues associated with laboratory-developed tests and varying levels of operator experience. This study aims to validate the accuracy attributes of peripheral blood neutrophil myeloperoxidase expression quantified by flow cytometric analysis in an independent multicentre sample. METHODS AND ANALYSIS: The MPO-MDS-Valid project is a cross-sectional diagnostic accuracy study comparing an index test to a reference standard. Consecutive adult patients referred for suspicion of MDS are being recruited at seven university hospitals and one cancer centre in France. At each site, flow cytometric analysis of peripheral blood samples is performed by operators who are blinded to the reference diagnosis. A central adjudication committee whose members are unaware of the index test results will determine the reference diagnosis of MDS, based on cytomorphological evaluation of bone marrow performed in duplicate by experienced hematopathologists. The target sample size is 400 patients and the anticipated study recruitment completion date is 31 December 2025. ETHICS AND DISSEMINATION: An institutional review board (Comité de Protection des Personnes Nord-Ouest III, Caen, France) approved the protocol, prior to the start of the study. Participants are recruited using an opt-out approach. Efforts will be made to publish the primary results within 6 months after study completion. TRIAL REGISTRATION NUMBER: NCT05175469.

Multifunctional Fe/Cu Dual-Single Atom Nanozymes with Enhanced Peroxidase Activity for Isoniazid Detection and Levofloxacin Degradation.

The design of single-atom nanozymes with dual active sites to increase their activity and for the detection and degradation of contaminants is rare and challenging. In this work, a single-atom nanozyme (FeCu-NC) based on a three-dimensional porous Fe/Cu dual active site was developed as a colorimetric sensor for both the quantitative analysis of isoniazid (INH) and the efficient degradation of levofloxacin (LEV). FeCu-NC was synthesized using a salt template and freeze-drying method with a three-dimensional hollow porous structure and dual active sites (Fe-Nx and Cu-Nx). In terms of morphology and structure, FeCu-NC exhibits excellent peroxidase-like activity and catalytic properties. Therefore, a colorimetric sensor was constructed around FeCu-NC for sensitive and rapid quantitative analysis of INH with a linear range of 0.9-10 µM and a detection limit as low as 0.3 µM, and the sensor was successfully applied to the analysis of INH in human urine. In addition, FeCu-NC promoted the efficient degradation of LEV by peroxymonosulfate activation, with a degradation rate of 90.4% for LEV at 30 min. This work sheds new light on the application of single-atom nanozymes to antibiotics for colorimetric sensing and degradation.

A highly effective peroxidase-mimic nanozyme of S, N-carbon dot-decorated cerium organic framework-based colorimetric detection of Hg2+ ion and thiophanate methyl.

In this study, we proposed a colorimetric probe as S, N-carbon dot-decorated Ce-MOF (S, N-CD@Ce-MOF) for the dual detection of mercury and thiophanate methyl (TM), which are simultaneously present pollutants in the environment and foodstuffs. These pollutants cause serious threats to human health, such as carcinogenicity and neurovirulence. Herein, we synthesized S, N-CD@Ce-MOF using the hydrothermal method and applied it to a "turn-off-on" probe to detect mercury and TM using the colorimetric method in water and food samples. S, N-CD@Ce-MOF shows excellent peroxidase activity by catalyzing the chromogenic substrate of 3,3',5,5'-tetramethylbenzidine (TMB), resulting in deep blue-colored oxidized TMB product (ox TMB) in the presence of H2O2 with a UV absorption wavelength at 654 nm. However, the addition of Hg(II) ions prohibits the oxidation of TMB by an electron transfer effect and easily binds with -S, -N-containing sites on the surface of carbon dots, obstructing the catalytic active sites and decreasing catalytic efficiency with weak UV absorption at 654 nm as a "turn-off". Subsequently, the addition of TM to the above sensing solution as a "turn-on" was triggered by the TM-Hg complex formation and permitted TMB oxidation with a strong absorption peak at 654 nm. Furthermore, this proposed sensor demonstrates a superior linear response to mercury ions and TM in the ranges from 0 to 15 µM and 0 to 14 µM, respectively. The developed colorimetric assay exhibits good sensitivity and selectivity against various possible interferences. Furthermore, we found that the limits of detection for Hg2+ and TM were as low as 0.01 µM and 0.03 µM, respectively. The developed sensor provides various benefits, such as cost-effectiveness, simplicity without a complex detection process, and naked-eye detection. Consequently, our proposed colorimetric technique worked well for the detection of Hg2+ in real water samples and TM in real apple and tomato juice.

AI-Powered Knowledge Base Enables Transparent Prediction of Nanozyme Multiple Catalytic Activity.

Nanozymes are unique materials with many valuable properties for applications in biomedicine, biosensing, environmental monitoring, and beyond. In this work, we developed a machine learning (ML) approach to search for new nanozymes and deployed a web platform, DiZyme, featuring a state-of-the-art database of nanozymes containing 1210 experimental samples, catalytic activity prediction, and DiZyme Assistant interface powered by a large language model (LLM). For the first time, we enable the prediction of multiple catalytic activities of nanozymes by training an ensemble learning algorithm achieving R2 = 0.75 for the Michaelis-Menten constant and R2 = 0.77 for the maximum velocity on unseen test data. We envision an accurate prediction of multiple catalytic activities (peroxidase, oxidase, and catalase) promoting novel applications for a wide range of surface-modified inorganic nanozymes. The DiZyme Assistant based on the ChatGPT model provides users with supporting information on experimental samples, such as synthesis procedures, measurement protocols, etc. DiZyme (dizyme.aicidlab.itmo.ru) is now openly available worldwide.

Nucleus-targeted carbon dots as peroxidase nanozyme for photoacoustic imaging and phototherapy of tumor.

High-purity carbon dots (CDs) with a highly π-conjugated sp2-hybridized graphite structure were prepared by the pulse electrolysis method using the graphite plate as raw material. Photoacoustic signal together with photothermal effect was found in the CDs-dispersed suspensions under near-infrared (NIR) irradiation. For the suspension with the CDs concentration of 500 µg/mL, the photothermal conversion efficiency is high up 64.3% and the solution's temperature can be increased to 82.2 °C under NIR irradiation. Moreover, CDs can be effectively endocytosed by human hepatoma (HepG2) cells with a few hours, act as peroxidase nanozyme to decompose H2O2 and facilitate the production of reactive oxygen species. Under NIR irradiation, CDs exhibit an outstanding apoptosis-inducing effect on HepG2 cells by the photothermal effect. In addition, in vivo experiments show that CDs can be used in photoacoustic imaging (PAI) and guiding the tumor treatment. As a result, the nucleus-targeted CDs with an unique combination of PAI and photothermal effect have potential in cancer diagnosis and treatment.

Sepsis compromises post-ischemic stroke neurological recovery and is associated with sex differences.

AIMS: Infection is a complication after stroke and outcomes vary by sex. Thus, we investigated if sepsis affects brain from ischemic stroke and sex involvement. MAIN METHODS: Male and female Wistar rats, were submitted to middle cerebral artery occlusion (MCAO) and after 7 days sepsis to cecal ligation and perforation (CLP). Infarct size, neuroinflammation, oxidative stress, and mitochondrial activity were quantified 24 h after CLP in the prefrontal cortex and hippocampus. Survival and neurological score were assessed up to 15 days after MCAO or 8 days after CLP (starting at 2 h after MCAO) and memory at the end. KEY FINDINGS: CLP decreased survival, increased neurological impairments in MCAO females. Early, in male sepsis following MCAO led to increased glial activation in the brain structures, and increased TNF-α and IL-1ß in the hippocampus. All groups had higher IL-6 in both tissues, but the hippocampus had lower IL-10. CLP potentiated myeloperoxidase (MPO) in the prefrontal cortex of MCAO male and female. In MCAO+CLP, only male increased MPO and nitrite/nitrate in hippocampus. Males in all groups had protein oxidation in the prefrontal cortex, but only MCAO+CLP in the hippocampus. Catalase decreased in the prefrontal cortex and hippocampus of all males and females, and MCAO+CLP only increased this activity in males. Female MCAO+CLP had higher prefrontal cortex complex activity than males. In MCAO+CLP-induced long-term memory impairment only in females. SIGNIFICANCE: The parameters evaluated for early sepsis after ischemic stroke show a worse outcome for males, while females are affected during long-term follow-up.

Exploring the biochemical dynamics in faba bean (Vicia faba L. minor) in response to Orobanche foetida Poir. parasitism under inoculation with different rhizobia strains.

In Tunisia, Orobanche foetida Poir. is considered an important agricultural biotic constraint on faba bean (Vicia faba L.) production. An innovative control method for managing this weed in faba bean is induced resistance through inoculation by rhizobia strains. In this study, we explored the biochemical dynamics in V. faba L. minor inoculated by rhizobia in response to O. foetida parasitism. A systemic induced resistant reaction was evaluated through an assay of peroxidase (POX), polyphenol oxidase (PPO) and phenyl alanine ammonialyase (PAL) activity and phenolic compound and hydrogen peroxide (H2O2) accumulation in faba bean plants infested with O. foetida and inoculated with rhizobia. Two rhizobia strains (Mat, Bj1) and a susceptible variety of cultivar Badi were used in a co-culture Petri dish experiment. We found that Mat inoculation significantly decreased O. foetida germination and the number of tubercles on the faba bean roots by 87% and 88%, respectively. Following Bj1 inoculation, significant decreases were only observed in O. foetida germination (62%). In addition, Mat and Bj1 inoculation induced a delay in tubercle formation (two weeks) and necrosis in the attached tubercles (12.50% and 4.16%, respectively) compared to the infested control. The resistance of V. faba to O. foetida following Mat strain inoculation was mainly associated with a relatively more efficient enzymatic antioxidative response. The antioxidant enzyme activity was enhanced following Mat inoculation of the infected faba bean plant. Indeed, increases of 45%, 67% and 86% were recorded in the POX, PPO and PAL activity, respectively. Improvements of 56% and 12% were also observed in the soluble phenolic and H2O2 contents. Regarding inoculation with the Bj1 strain, significant increases were only observed in soluble phenolic and H2O2 contents and PPO activity (especially at 45 days after inoculation) compared to the infested control. These results imply that inoculation with the rhizobia strains (especially Mat) induced resistance and could bio-protect V. faba against O. foetida parasitism by inducing systemic resistance, although complete protectionwas not achieved by rhizobia inoculation. The Mat strain could be used as a potential candidate for the development of an integrated method for controlling O. foetida parasitism in faba bean.

Staphylococcal peroxidase inhibitor (SPIN): Residue-level investigation of the helical bundle domain.

Myeloperoxidase is a critical component of the antibacterial arsenal of neutrophils, whereby it consumes H2O2 as an oxidant to convert halogen and pseudohalogen anions into cytotoxic hypohalous acids. Following phagocytosis by neutrophils, the human pathogen Staphylococcus aureus secretes a potent myeloperoxidase inhibitory protein, called SPIN, as part of its immune evasion repertoire. The matured S. aureus SPIN polypeptide consists of only 73 residues yet contains two functional domains: whereas the 60 residue C-terminal helical bundle domain is responsible for MPO binding, the 13 residue N-terminal domain is required to inhibit MPO. Previous studies have informed understanding of the SPIN N-terminal domain, but comparatively little is known about the helical domain insofar as the contribution of individual residues is concerned. To address this limitation, we carried out a residue-level structure/function investigation on the helical bundle domain of S. aureus SPIN. Using sequence conservation and existing structures of SPIN bound to human MPO as a guide, we selected residues L49, E50, H51, E52, Y55, and Y75 for interrogation by site-directed mutagenesis. We found that loss of L49 or E52 reduced SPIN activity by roughly an order of magnitude, but that loss of Y55 or H51 caused progressively greater loss of inhibitory potency. Direct binding studies by SPR showed that loss of inhibitory potency in these SPIN mutants resulted from a diminished initial interaction between the inhibitor and MPO. Together, our studies provide new insights into the structure/function relationships of SPIN and identify positions Y55 and H51 as critical determinants of SPIN function.

Metal-polyphenol coordination nanosheets with synergistic peroxidase-like and photothermal properties for efficient antibacterial treatment.

Bacterial infections pose a serious threat to human health and socioeconomics worldwide. In the post-antibiotic era, the development of novel antimicrobial agents remains a challenge. Polyphenols are natural compounds with a variety of biological activities such as intrinsic antimicrobial activity and antioxidant properties. Metal-polyphenol obtained by chelation of polyphenol ligands with metal ions not only possesses efficient antimicrobial activity but also excellent biocompatibility, which has great potential for application in biomedical and food packaging fields. Herein, we developed metal-polyphenol coordination nanosheets named copper oxidized tannic acid quinone (CuTAQ) possessing efficient antibacterial and anti-biofilm effects, which was synthesized by a facile one-pot method. The synthesis was achieved by chelation of partially oxidized tannic acid (TA) with Cu2+ under mild conditions, which supports low-cost and large-scale production. It was demonstrated that CuTAQ exhibited high antibacterial activity via disrupting the integrity of bacterial cell membranes, inducing oxidative stress, and interfering with metabolism. In addition, CuTAQ exhibits excellent peroxidase catalytic activity and photothermal conversion properties, which play a significant role in enhancing its bactericidal and biofilm scavenging abilities. This study provides insights for rational design of innovative metal-polyphenol nanomaterials with efficient antimicrobial properties.

Effectiveness of a tissue conditioner containing antifungals in a rat model of denture stomatitis.

AIM: This study investigated the effectiveness of a drug-modified tissue conditioner in an animal model of denture stomatitis. METHODS AND RESULTS: Wistar rats wore a Candida albicans-contaminated palatal device for 4 days. Next, nystatin (Nys) or chlorhexidine (Chx) were added to a tissue conditioner in their raw or ß-cyclodextrin-complexed (ßCD) forms at their minimum inhibitory concentrations. As controls, one group was not subjected to any procedure (NC), one group used sterile devices, one group had denture stomatitis but was not treated (DS), and another had the devices relined with the tissue conditioner without the addition of any drug (Soft). After 4 days of treatment, treatment effectiveness was assessed visually, histologically, and through CFU count, and myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) assays. Rats from the Soft, Nys, Nys:ßCD, and Chx groups presented a significant decrease in the microbial load compared with the untreated group. Treatment groups showed lower MPO and NAG activity compared to the non-treated group. CONCLUSIONS: The addition of antifungals to a soft tissue conditioner can be a promising approach for denture stomatitis treatment.

Porous reticular Co@Fe metal-organic gel: dual-function simulated peroxidase nanozyme for both colorimetric sensing and antibacterial applications.

Constructing metal-organic gels (MOGs) with enzyme-catalyzed activity and studying their catalytic mechanism are crucial for the development of novel nanozyme materials. In this study, a Co@Fe MOG with excellent peroxidase activity was developed by a simple and mild one-pot process. The results showed that the material exhibited almost a single peroxidase activity under optimal pH conditions, which allowed it to attract and oxidize the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB). Based on the active electron transfer between the metal centers and the organic ligand in the synthetic material, the Co@Fe MOG-H2O2-TMB system was verified to be able to detect H2O2 and citric acid (CA). The catalytic microenvironment formed by the adsorption and the catalytic center accelerated the electron-transfer rate, which expedited the generation of hydroxyl radicals (˙OH, a kind of reactive oxygen species (ROS)) in the presence of H2O2. The persistence and high intensity of ˙OH generation were proven, which would endow Co@Fe MOG with a certain antibacterial ability, promoting the healing of bacteria-infected wounds. In conclusion, this study contributes to the development efforts toward the application systems of nanozymes for marker detection and antibacterial activity.

Active site-tuned high peroxidase-like activity nanozyme for on-the-spot detection of saliva total antioxidant capacity using smartphone devices.

Metal-Organic Framework (MOF) based nanozymes with clear structure are beneficial for exploration of structural-performance and exhibit broad prospects in improving activity. In this study, the prepared bimetallic Fe3Ni-MOF nanozyme was superior to single metal MOF in the peroxidase-like activity. Subsequently, a derivative nanozyme (Fe3Ni-MOF-Ar) was prepared by pyrolysis using Fe3Ni-MOF as the precursor in argon atomoshere with controlled temperature. The investigated of Fe3Ni-MOF-Ar revealed that the irregular macroporous state and the presence of heterovalent FeIII/FeII sites of Fe3Ni-MOF-Ar enable the retention, exposure, and electronic structure regulation of active sites, promoting the dual mechanism (the generation of •OH and electron transfer mechanism) and significantly increasing the peroxidase-like activity. Fe3Ni-MOF-Ar exhibited a strong affinity for substrate H2O2, which is higher than horseradish peroxidase. Ascorbic acid and cysteine are typical substances of antioxidants. Fe3Ni-MOF-Ar was used for sensitive colorimetric detection of ascorbic acid and cysteine, and the detection limit was as low as 150 and 60 nM. In addition, the smartphone devices was used to detection of antioxidant equivalent ascorbic acid, with a detection range of 0.5-120 µM. Fe3Ni-MOF-Ar nanozyme is feasible for sensitive detection of saliva total antioxidant capacity.

Bifunctional oxidase-peroxidase mimicking Fe-Ce MOF on paper-based analytical devices to intensify luminol chemiluminescence: Application for measuring different sugars with a smartphone readout.

This study presents a potent paper-based analytical device (PAD) for quantifying various sugars using an innovative bi-nanozyme made from a 2-dimensional Fe/Ce metal-organic framework (FeCe-BTC). The MOF showed excellent bifunctional peroxidase-oxidase activities, efficiently catalyzing luminol's chemiluminescence (CL) reaction. As a peroxidase-like nanozyme, FeCe-BTC could facilitate the dissociation of hydrogen peroxide (H2O2) into hydroxyl radicals, which then oxidize luminol. Additionally, it was also discovered that when reacting with H2O2, the MOF turns into a mixed-valence MOF, and acts as an oxidase nanozyme. This activity is caused by the generated Ce4+ ions in the structure of MOF that can directly oxidize luminol. The MOF was directly synthesized on the PAD and cascaded with specific natural enzymes to establish simple, rapid, and selective CL sensors for the measurement of different sugars. A cell phone was also used to record light intensities, which were then correlated to the analyte concentration. The designed PAD showed a wide linear range of 0.1-10 mM for glucose, fructose, and sucrose, with detection limits of 0.03, 0.04, and 0.04 mM, respectively. It showed satisfactory results in food and biological samples with recovery values ranging from 95.8 to 102.4 %, which makes it a promising candidate for point-of-care (POC) testing for food control and medicinal purposes.

Myricetin reduces neutrophil extracellular trap release in a rat model of rheumatoid arthritis, which is associated with a decrease in disease severity.

Rheumatoid arthritis (RA) is a chronic disease characterized by joint inflammation and severe disability. However, there is a lack of safe and effective drugs for treating RA. In our previous study, we discovered that myricetin (MC) and celecoxib have a synergistic effect in the treatment of RA. We conducted in vitro and in vivo experiments to further investigate the effects and mechanisms of action of MC. Our findings demonstrated that MC treatment effectively reduced the release of neutrophil extracellular traps (NETs) and alleviated the inflammatory response in RA. Mechanistic studies showed that MC prevents the entry of PADI4 and MPO into the cell nucleus, thereby protecting DNA from decondensation. In a rat arthritis model, MC improved histological changes in ankle joints and suppressed NET-related signaling factors. In conclusion, MC protects the ankle joints against arthritis by inhibiting MPO and PADI4, thereby reducing NET release. The pharmacological mechanism of MC in RA involves the inhibition of NET release.

Exploring the role of myeloperoxidase in the atherosclerotic process in hypoxic mice based on the MAPK signaling pathway.

Atherosclerosis (AS) is the common pathophysiological basis of various cardiovascular diseases and the leading cause of death from cardiovascular disease worldwide. When the body is in a hypoxic environment, enhanced oxidative stress and significant accumulation of reactive oxygen species (ROS) in tissue cells exacerbate the inflammatory response, resulting in increased release of myeloperoxidase (MPO), catalyzing the formation of large quantities of hypochlorous acid (HOCl), further oxidative modification of low-density lipoprotein (LDL), and exacerbating the formation and progression of atherosclerotic plaques. The MAPK signaling pathway is important in oxidative stress-mediated promotion of atherogenesis. MPO -/- mice were used in this study to establish a hypoxia model simulating 5000 m altitude and a Western high-fat diet-induced atherosclerosis model for 12 weeks. Exploring the role of MPO in the atherosclerotic process in hypoxic mice by observing the MAPK signaling pathway to provide a therapeutic target for the prevention and treatment of hypoxic atherosclerotic disease in the plateau. We found that hypoxia promotes the formation of atherosclerosis in mice, and the mechanism may be that increased MPO in vivo promotes an inflammatory response, which plays a crucial role in the formation of atherosclerosis. In addition, hypoxia further exacerbates plaque instability by activating the MAPK signaling pathway to upregulate vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP9), which in turn promotes angiogenesis within the plaque. Therefore, a potential target for preventing and treating hypoxic atherosclerotic disease is the inhibition of MPO.