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ACS Nano Aug 2023Treatment of diabetic foot ulcers (DFU) needs to reduce inflammation, relieve hypoxia, lower blood glucose, promote angiogenesis, and eliminate pathogenic bacteria, but...
Treatment of diabetic foot ulcers (DFU) needs to reduce inflammation, relieve hypoxia, lower blood glucose, promote angiogenesis, and eliminate pathogenic bacteria, but the therapeutic efficacy is greatly limited by the diversity and synergy of drug functions as well as the DFU microenvironment itself. Herein, an ultrasound-augmented multienzyme-like nanozyme hydrogel spray was developed using hyaluronic acid encapsulated l-arginine and ultrasmall gold nanoparticles and CuO nanoparticles coloaded phosphorus doped graphitic carbon nitride nanosheets (ACPCAH). This nanozyme hydrogel spray possesses five types of enzyme-like activities, including superoxide dismutase (SOD)-, catalase (CAT)-, glucose oxidase (GOx)-, peroxidase (POD)-, and nitric oxide synthase (NOS)-like activities. The kinetics and reaction mechanism of the sonodynamic/sonothermal synergistic enhancement of the SOD-CAT-GOx-POD/NOS cascade reaction of ACPCAH are fully investigated. Both in vitro and in vivo tests demonstrate that this nanozyme hydrogel spray can be activated by the DFU microenvironment to reduce inflammation, relieve hypoxia, lower blood glucose, promote angiogenesis, and eliminate pathogenic bacteria, thus accelerating diabetic wound healing effectively. This study highlights a competitive approach based on multienzyme-like nanozymes for the development of all-in-one DFU therapies.
Topics: Humans; Hydrogels; Blood Glucose; Gold; Metal Nanoparticles; Diabetes Mellitus; Wound Healing; Peroxidase; Superoxide Dismutase; Antioxidants; Glucose Oxidase
PubMed: 37535449
DOI: 10.1021/acsnano.3c04134 -
International Journal of Molecular... Oct 2023Neutrophils are the principal trouper of the innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure... (Review)
Review
Neutrophils are the principal trouper of the innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure called neutrophil extracellular traps (NETs) as a part of their defensive strategy against microbial pathogen attack. This web-like architecture includes a DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), neutrophil elastase (NE), histones and deploys in the entrapment and clearance of encountered pathogens. Thus NETs play an inevitable beneficial role in the host's protection. However, recent accumulated evidence shows that dysregulated and enhanced NET formation has various pathological aspects including the promotion of sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, and cancer diseases, and the list is increasing gradually. In this review, we summarize the NET-mediated pathophysiology of different diseases and focus on some updated potential therapeutic approaches against NETs.
Topics: Humans; Extracellular Traps; Neutrophils; Histones; Sepsis; Peroxidase
PubMed: 37958788
DOI: 10.3390/ijms242115805 -
Clinical Chemistry and Laboratory... Jul 2023Detection of hemoglobin (Hb) and red blood cells in urine (hematuria) is characterized by a large number of pitfalls. Clinicians and laboratory specialists must be... (Review)
Review
Detection of hemoglobin (Hb) and red blood cells in urine (hematuria) is characterized by a large number of pitfalls. Clinicians and laboratory specialists must be aware of these pitfalls since they often lead to medical overconsumption or incorrect diagnosis. Pre-analytical issues (use of vacuum tubes or urine tubes containing preservatives) can affect test results. In routine clinical laboratories, hematuria can be assayed using either chemical (test strips) or particle-counting techniques. In cases of doubtful results, Munchausen syndrome or adulteration of the urine specimen should be excluded. Pigmenturia (caused by the presence of dyes, urinary metabolites such as porphyrins and homogentisic acid, and certain drugs in the urine) can be easily confused with hematuria. The peroxidase activity (test strip) can be positively affected by the presence of non-Hb peroxidases (e.g. myoglobin, semen peroxidases, bacterial, and vegetable peroxidases). Urinary pH, haptoglobin concentration, and urine osmolality may affect specific peroxidase activity. The implementation of expert systems may be helpful in detecting preanalytical and analytical errors in the assessment of hematuria. Correcting for dilution using osmolality, density, or conductivity may be useful for heavily concentrated or diluted urine samples.
Topics: Humans; Hematuria; Peroxidase; Hemoglobins; Erythrocytes; Osmolar Concentration
PubMed: 37079906
DOI: 10.1515/cclm-2023-0260 -
The Lancet. Rheumatology May 2024Myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-ANCA-associated vasculitis) is one of two major ANCA-associated... (Review)
Review
Myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-ANCA-associated vasculitis) is one of two major ANCA-associated vasculitis variants characterised by systemic necrotising vasculitis with few or no immune deposits. MPO-ANCA-associated vasculitis predominantly affects small blood vessels and, in contrast to its counterpart proteinase 3-ANCA-associated vasculitis, is generally not associated with granulomatous inflammation. The kidneys and lungs are the most commonly affected organs. The pathogenesis of MPO-ANCA-associated vasculitis is characterised by loss of tolerance to the neutrophil enzyme MPO. This loss of tolerance leads to a chronic immunopathological response where neutrophils become both the target and effector of autoimmunity. MPO-ANCA drives neutrophil activation, leading in turn to tissue and organ damage. Clinical trials have improved the therapeutic approach to MPO-ANCA-associated vasculitis. However, there remains substantial unmet need regarding relapse frequency, toxicity of current treatment, and long-term morbidity. In this Series paper, we present the current state of research regarding pathogenesis, diagnosis, and treatment of MPO-ANCA-associated vasculitis.
Topics: Humans; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Peroxidase
PubMed: 38574743
DOI: 10.1016/S2665-9913(24)00025-0 -
ACS Nano Jul 2023Nanozymes constitute an emerging class of nanomaterials with enzyme-like characteristics. Over the past 15 years, more than 1200 nanozymes have been developed, and they... (Review)
Review
Nanozymes constitute an emerging class of nanomaterials with enzyme-like characteristics. Over the past 15 years, more than 1200 nanozymes have been developed, and they have demonstrated promising potentials in broad applications. With the diversification and complexity of its applications, traditional empirical and trial-and-error design strategies no longer meet the requirements for efficient nanozyme design. Thanks to the rapid development of computational chemistry and artificial intelligence technologies, first-principles methods and machine-learning algorithms are gradually being adopted as a more efficient and easier means to assist nanozyme design. This review focuses on the potential elementary reaction mechanisms in the rational design of nanozymes, including peroxidase (POD)-, oxidase (OXD)-, catalase (CAT)-, superoxide dismutase (SOD)-, and hydrolase (HYL)-like nanozymes. The activity descriptors are introduced, with the aim of providing further guidelines for nanozyme active material screening. The computing- and data-driven approaches are thoroughly reviewed to give a proposal on how to proceed with the next-generation paradigm rational design. At the end of this review, personal perspectives on the prospects and challenges of the rational design of nanozymes are put forward, hoping to promote the further development of nanozymes toward superior application performance in the future.
Topics: Artificial Intelligence; Catalysis; Nanostructures; Peroxidase; Peroxidases
PubMed: 37399457
DOI: 10.1021/acsnano.3c04378 -
Phytotherapy Research : PTR Nov 2023Myocardial infarction (MI) is a common disease with high morbidity and mortality. Curdione is a sesquiterpenoid from Radix Curcumae. The current study is aimed to...
Myocardial infarction (MI) is a common disease with high morbidity and mortality. Curdione is a sesquiterpenoid from Radix Curcumae. The current study is aimed to investigate the protective effect and mechanism of curdione on ferroptosis in MI. Isoproterenol (ISO) was used to induce MI injury in mice and H9c2 cells. Curdione was orally given to mice once daily for 7 days. Echocardiography, biochemical kits, and western blotting were performed on the markers of cardiac ferroptosis. Curdione at 50 and 100 mg/kg significantly alleviated ISO-induced myocardial injury. Curdione and ferrostatin-1 significantly attenuated ISO-induced H9c2 cell injury. Curdione effectively suppressed cardiac ferroptosis, evidenced by decreasing malondialdehyde and iron contents, and increasing glutathione (GSH) level, GSH peroxidase 4 (GPX4), and ferritin heavy chain 1 expression. Importantly, drug affinity responsive target stability, molecular docking, and surface plasmon resonance technologies elucidated the direct target Keap1 of curdione. Curdione disrupted the interaction between Keap1 and thioredoxin1 (Trx1) but enhanced the Trx1/GPX4 complex. In addition, curdione-derived protection against ISO-induced myocardial ferroptosis was blocked after overexpression of Keap1, while enhanced after Keap1 silence in H9c2 cells. These findings demonstrate that curdione inhibited ferroptosis in ISO-induced MI via regulating Keap1/Trx1/GPX4 signaling pathway.
Topics: Animals; Mice; Peroxidase; Isoproterenol; Ferroptosis; Kelch-Like ECH-Associated Protein 1; Molecular Docking Simulation; NF-E2-Related Factor 2; Peroxidases; Myocardial Infarction; Signal Transduction; Glutathione
PubMed: 37500597
DOI: 10.1002/ptr.7964 -
Kidney International Mar 2024
Topics: Humans; Antibodies, Antineutrophil Cytoplasmic; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Peroxidase
PubMed: 38388102
DOI: 10.1016/j.kint.2023.10.008 -
Nanoscale Aug 2023In recent years, nanozymes have attracted enormous attention due to their effectiveness in promoting various catalytic reactions. To date, thousands of nanozymes have... (Review)
Review
In recent years, nanozymes have attracted enormous attention due to their effectiveness in promoting various catalytic reactions. To date, thousands of nanozymes have been discovered, including oxidase-like nanozymes, peroxidase-like nanozymes, and catalase-like nanozymes, covering noble metal, transition metal, and carbon nanomaterials. These nanozymes have been widely applied in various fields, including environmental protection, biosensing and nanomedicine. There are many reviews about this rising star being used in analytical chemistry. However, few works about nanozymes were related to cancer therapy. In this study, we comprehensively summarize the latest research advances on the strategies for cancer therapy based on different nanozymes. With traditional cancer treatment (including chemotherapy, radiotherapy, phototherapy), nanozyme catalytic therapy exhibited a synergistic effect for limiting the growth of tumors. Opportunities and trends for nanozymes in future cancer therapy are also discussed.
Topics: Nanostructures; Peroxidase; Peroxidases; Catalysis; Carbon; Neoplasms
PubMed: 37462391
DOI: 10.1039/d3nr01976d -
JACC. Heart Failure Jul 2023Systemic microvascular dysfunction and inflammation are postulated to play a pathophysiologic role in heart failure with preserved ejection fraction (HFpEF). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Systemic microvascular dysfunction and inflammation are postulated to play a pathophysiologic role in heart failure with preserved ejection fraction (HFpEF).
OBJECTIVES
This study aimed to identify biomarker profiles associated with clinical outcomes in HFpEF and investigate how inhibition of the neutrophil-derived reactive oxygen species-producing enzyme, myeloperoxidase, affects these biomarkers.
METHODS
Using supervised principal component analyses, the investigators assessed the associations between baseline plasma proteomic Olink biomarkers and clinical outcomes in 3 independent observational HFpEF cohorts (n = 86, n = 216, and n = 242). These profiles were then compared with the biomarker profiles discriminating patients treated with active drug vs placebo in SATELLITE (Safety and Tolerability Study of AZD4831 in Patients With Heart Failure), a double-blind randomized 3-month trial evaluating safety and tolerability of the myeloperoxidase inhibitor AZD4831 in HFpEF (n = 41). Pathophysiological pathways were inferred from the biomarker profiles by interrogation of the Ingenuity Knowledge Database.
RESULTS
TNF-R1, TRAIL-R2, GDF15, U-PAR, and ADM were the top individual biomarkers associated with heart failure hospitalization or death, and FABP4, HGF, RARRES2, CSTB, and FGF23 were associated with lower functional capacity and poorer quality of life. AZD4831 downregulated many markers (most significantly CDCP1, PRELP, CX3CL1, LIFR, VSIG2). There was remarkable consistency among pathways associated with clinical outcomes in the observational HFpEF cohorts, the top canonical pathways being associated with tumor microenvironments, wound healing signaling, and cardiac hypertrophy signaling. These pathways were predicted to be downregulated in AZD4831 relative to placebo-treated patients.
CONCLUSIONS
Biomarker pathways that were most strongly associated with clinical outcomes were also the ones reduced by AZD4831. These results support the further investigation of myeloperoxidase inhibition in HFpEF.
Topics: Humans; Antigens, Neoplasm; Biomarkers; Cell Adhesion Molecules; Heart Failure; Peroxidase; Proteomics; Quality of Life; Stroke Volume
PubMed: 37140510
DOI: 10.1016/j.jchf.2023.03.002 -
Nephrologie & Therapeutique Jun 2023ANCA vasculitides (AAV) are autoimmune diseases responsible for damage to small-size vessels. Three entities are distinguished from clinical, histological and biological...
ANCA vasculitides (AAV) are autoimmune diseases responsible for damage to small-size vessels. Three entities are distinguished from clinical, histological and biological criteria: micropolyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The neutrophil-ANCA couple is central to the pathophysiology of AAV. The mechanisms that lead to the breakdown of tolerance to myeloperoxidase or proteinase-3 remain hypothetical, however, probably multifactorial, occurring on a predisposing genetic background. The understanding of the injury mechanisms involved in AAV has made great progress thanks to the study of a murine model of immunization against myeloperoxidase. This work has made it possible to show the central role of the PNN in vivo, which are activated under sterile conditions, under the effect of the ANCAs which recognize the self-antigen expressed on their surface. Understanding the role of the alternative complement pathway and in particular that of C5a, a powerful anaphylatoxin, was a major advance. C5a acts as an amplifying factor for PNN activation and blocking its receptor (C5aR) prevents the occurrence of vasculitis lesions in the mouse model. These discoveries led to therapeutic trials in humans highlighting the interest of blocking C5aR and validating this therapeutic strategy. It should be emphasized that the AAV study model is, above all, an anti-MPO model and that the mechanisms involved in anti-PR3 ANCA or ANCA negative vasculitis remain very hypothetical. Finally, the mechanisms that account for the heterogeneity relating to the presentation or severity of AAV remain poorly understood.
Topics: Humans; Animals; Mice; Antibodies, Antineutrophil Cytoplasmic; Peroxidase; Churg-Strauss Syndrome; Granulomatosis with Polyangiitis; Autoantigens
PubMed: 37381742
DOI: 10.1684/ndt.2023.29