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Journal of Materials Chemistry. B Jul 2023Nanozymes are nanoscale materials that display enzyme-like properties, which have been improved to eliminate the limitations of natural enzymes and further broaden the... (Review)
Review
Nanozymes are nanoscale materials that display enzyme-like properties, which have been improved to eliminate the limitations of natural enzymes and further broaden the use of conventional artificial enzymes. In the last decade, the research and exploration of nanozymes have attracted considerable attention in the chemical and biological fields, especially in the fields of biomedicine and tumor therapy. To date, plenty of nanozymes have been developed with the single or multiple activities of natural enzymes, including peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), glucose oxidase (GOx). Tumor-characteristic metabolites can be transformed into toxic substances under the catalysis of nanozymes to kill tumor cells. However, the therapeutic effects of nanozymes greatly depend on their catalytic activity, which displays a lot of differences and . Moreover, the complex tumor environment (low pH, high HO and GSH concentration, hypoxia, ) plays an important role in affecting their catalytic activity. Besides, the uncontrollable catalysis of nanozymes may lead to the destruction of normal tissues. To solve these problems, researchers have exploited several imaging methods to monitor the reaction processes during catalysis, including optical imaging methods (fluorescence and chemiluminescence), photoacoustic imaging, and magnetic resonance imaging. In this review, we have summarized the development of tumor treatment using nanozymes in recent years, along with the current imaging tools to monitor the catalyzing activity of nanozymes. Representative examples have been elaborated on to show the current development of these imaging tools. We hope this review will provide some instructive perspectives on the development of nanozymes and promote the applications of imaging-guided tumor therapeutics.
Topics: Humans; Nanostructures; Hydrogen Peroxide; Glucose Oxidase; Peroxidase; Neoplasms
PubMed: 37254674
DOI: 10.1039/d3tb00464c -
International Journal of Molecular... Jul 2023Salivary myeloperoxidase (MPO) is a key mediator of the oral immune system, acting as an enzyme that utilises HO to generate molecules with high bactericidal activity.... (Review)
Review
Salivary myeloperoxidase (MPO) is a key mediator of the oral immune system, acting as an enzyme that utilises HO to generate molecules with high bactericidal activity. While MPO determination in plasma is quite common, the use of saliva is still rare. Our systematic review was designed to answer the question "Are salivary levels of myeloperoxidase altered in patients with systemic diseases?". Following the inclusion and exclusion criteria, we included twenty-six studies. Altered MPO levels in saliva were most commonly found in patients with cardiovascular and gastrointestinal diseases. Most studies concerned unstimulated whole saliva, and only a few of them stimulated, mainly by chewing paraffin. Enzyme-linked immunosorbent assay (ELISA) was the most common method for determination of MPO concentrations in saliva. Increased salivary MPO levels were more often observed for inflammatory diseases, except patients with inflammatory bowel diseases who were eligible for biologic therapy. In conclusion, MPO could be altered in the saliva of patients with systematic diseases, especially cardiovascular or gastrointestinal diseases. However, further investigations are recommended to validate these outcomes.
Topics: Humans; Enzyme-Linked Immunosorbent Assay; Hydrogen Peroxide; Peroxidase; Saliva
PubMed: 37569455
DOI: 10.3390/ijms241512078 -
Basic Research in Cardiology Sep 2023Cardiotoxicity is a major complication of anthracycline therapy that negatively impacts prognosis. Effective pharmacotherapies for prevention of anthracycline-induced...
Cardiotoxicity is a major complication of anthracycline therapy that negatively impacts prognosis. Effective pharmacotherapies for prevention of anthracycline-induced cardiomyopathy (AICM) are currently lacking. Increased plasma levels of the neutrophil-derived enzyme myeloperoxidase (MPO) predict occurrence of AICM in humans. We hypothesized that MPO release causally contributes to AICM. Mice intravenously injected with the anthracycline doxorubicin (DOX) exhibited higher neutrophil counts and MPO levels in the circulation and cardiac tissue compared to saline (NaCl)-treated controls. Neutrophil-like HL-60 cells exhibited increased MPO release upon exposition to DOX. DOX induced extensive nitrosative stress in cardiac tissue alongside with increased carbonylation of sarcomeric proteins in wildtype but not in Mpo mice. Accordingly, co-treatment of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with DOX and MPO aggravated loss of hiPSC-CM-contractility compared to DOX treatment alone. DOX-treated animals exhibited pronounced cardiac apoptosis and inflammation, which was attenuated in MPO-deficient animals. Finally, genetic MPO deficiency and pharmacological MPO inhibition protected mice from the development of AICM. The anticancer efficacy of DOX was unaffected by MPO deficiency. Herein we identify MPO as a critical mediator of AICM. We demonstrate that DOX induces cardiac neutrophil infiltration and release of MPO, which directly impairs cardiac contractility through promoting oxidation of sarcomeric proteins, cardiac inflammation and cardiomyocyte apoptosis. MPO thus emerges as a promising pharmacological target for prevention of AICM.
Topics: Animals; Humans; Mice; Anthracyclines; Cardiomyopathies; Doxorubicin; Induced Pluripotent Stem Cells; Inflammation; Peroxidase
PubMed: 37656254
DOI: 10.1007/s00395-023-01006-0 -
Journal of Autoimmunity Sep 2023Antimyeloperoxidase (anti-MPO) and antiproteinase 3 (anti-PR3) antibodies are found in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). We investigated...
Antimyeloperoxidase (anti-MPO) and antiproteinase 3 (anti-PR3) antibodies are found in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). We investigated the effect of both anti-MPO and anti-PR3 IgG on human monocytes. Peripheral blood monocytes were cultured under a range of conditions that included TLR agonists, anti-MPO IgG and anti-PR3 IgG with appropriate controls. Experiments included whole transcriptome profiling and an assessment of the role of Fc receptors. When monocytes were stimulated with LPS or R848, anti-MPO but not anti-PR3 IgG, caused a reduction in IL-10 secretion and had a profound effect on cell-surface marker expression. Anti-MPO but not anti-PR3 IgG enhanced monocyte survival in the absence of TLR stimulation. These effects depended on the Fc receptor CD32a. With TLR stimulation, the effect of anti-MPO but not anti-PR3 IgG on the transcriptional response at 6 h was variable, but we identified a core set of transcripts likely to be important. Without TLR stimulation, there was a robust effect of anti-MPO but not anti-PR3 IgG on the transcriptional response at 24 h, and there was a highly significant enrichment of genes encoding extracellular matrix and extracellular matrix-associated proteins. Analysis with nCounter confirmed many of the differentially expressed transcripts and supported a role for CD32a. These data show that anti-MPO, but not anti-PR3 IgG, from patients with AAV has wide-ranging effects on monocytes which depend on CD32a. The activation of a profibrotic transcriptional response by anti-MPO but not anti-PR3 IgG may give insights into the differences in disease phenotype.
Topics: Humans; Monocytes; Myeloblastin; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Receptors, Fc; Immunoglobulin G; Antibodies, Antineutrophil Cytoplasmic; Peroxidase
PubMed: 37331172
DOI: 10.1016/j.jaut.2023.103060 -
Rheumatology (Oxford, England) Nov 2023
Topics: Humans; Antibodies, Antineutrophil Cytoplasmic; Granulomatosis with Polyangiitis; Peroxidase
PubMed: 37137279
DOI: 10.1093/rheumatology/kead173 -
Terapevticheskii Arkhiv Jun 2024To evaluate the levels of MPO-DNA complex in patients with systemic lupus erythematosus (SLE) and its association with the presence of lupus nephritis (LN).
AIM
To evaluate the levels of MPO-DNA complex in patients with systemic lupus erythematosus (SLE) and its association with the presence of lupus nephritis (LN).
MATERIALS AND METHODS
The study included 77 patients with SLE, of whom 30 had SLE without anti phospholipid syndrome (APS), 47 had SLE with APS, and 20 were healthy individuals serving as the control group. The MPO-DNA complex in the serum was investigated using ELISA.
RESULTS
The levels of MPO-DNA complex in serum were significantly higher in patients with SLE compared to healthy controls (=0.001). Among the patients with SLE, 30 (39%) had elevated levels of MPO-DNA complex. The presence of elevated MPO-DNA complex was significantly associated with the presence of a history of LN (=0.009). Moreover, among the patients included in the study, 20 had active LN, and patients with elevated MPO-DNA complex levels were more likely to have active LN than patients without elevated MPO-DNA complex concentrations [12 (40%) of 30 vs 8 (17%) of 47, χ=5.029; =0.034]. An association was found between elevated levels of MPO-DNA complex and the presence of proteinuria, hematuria, cellular hematic/granular casts and aseptic leukocyturia. A direct correlation of MPO-DNA complex with SLEDAI-R was found in patients with active LN (=0.497; =0.026).
CONCLUSION
Elevated levels of MPO-DNA complex were detected in 39% of patients with SLE. These patients had a higher prevalence of LN in their medical history and at the time of inclusion in the study. The correlation between MPO-DNA complex levels and the activity of LN according to SLEDAI-R indicates the potential role of MPO-DNA complex as a biomarker for assessing the activity of renal damage in SLE.
Topics: Humans; Lupus Nephritis; Female; Adult; Male; DNA; Peroxidase; Extracellular Traps; Middle Aged; Lupus Erythematosus, Systemic; Biomarkers
PubMed: 38829805
DOI: 10.26442/00403660.2024.05.202699 -
International Journal of Molecular... Oct 2023Retinal inflammation is a central feature of ocular neovascular diseases such as diabetic retinopathy and retinopathy of prematurity, but the contribution of neutrophils...
Retinal inflammation is a central feature of ocular neovascular diseases such as diabetic retinopathy and retinopathy of prematurity, but the contribution of neutrophils to this process is not fully understood. We studied oxygen-induced retinopathy (OIR) which develops in two phases, featuring hyperoxia-induced retinal vaso-obliteration in phase I, followed by retinal neovascularization in phase II. As neutrophils are acute responders to tissue damage, we evaluated whether neutrophil depletion with an anti-Ly6G mAb administered in phase I OIR influenced retinal inflammation and vascular injury. Neutrophils were measured in blood and spleen via flow cytometry, and myeloperoxidase, an indicator of neutrophil activity, was evaluated in the retina using Western blotting. Retinal vasculopathy was assessed by quantitating vaso-obliteration, neovascularization, vascular leakage, and VEGF levels. The inflammatory factors, TNF, MCP-1, and ICAM-1 were measured in retina. In the OIR controls, neutrophils were increased in the blood and spleen in phase I but not phase II OIR. In OIR, the anti-Ly6G mAb reduced neutrophils in the blood and spleen, and myeloperoxidase, inflammation, and vasculopathy in the retina. Our findings revealed that the early rise in neutrophils in OIR primes the retina for an inflammatory and angiogenic response that promotes severe damage to the retinal vasculature.
Topics: Animals; Mice; Oxygen; Neutrophils; Peroxidase; Retinopathy of Prematurity; Vascular Endothelial Growth Factor A; Animals, Newborn; Retina; Neovascularization, Pathologic; Retinal Neovascularization; Inflammation; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 37958664
DOI: 10.3390/ijms242115680 -
European Journal of Heart Failure Sep 2023Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity-induced systemic inflammation, which... (Randomized Controlled Trial)
Randomized Controlled Trial
Rationale and design of ENDEAVOR: A sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction.
AIMS
Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity-induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b-3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF.
METHODS
In phase 2b, approximately 660 patients with heart failure and ejection fraction >40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6-min walk distance (6MWD) of 30-400 m with a <50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ-TSS. The sample size provides 85% power to detect placebo-adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ-TSS at overall two-sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo.
CONCLUSION
ENDEAVOR is the first phase 2b-3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF.
Topics: Humans; Heart Failure; Stroke Volume; Exercise Tolerance; Peroxidase; Comorbidity; Heart Diseases
PubMed: 37470101
DOI: 10.1002/ejhf.2977 -
Advanced Healthcare Materials Oct 2023Reactive oxygen species (ROS)-involved tumor therapeutic strategy, chemodynamic therapy (CDT), has attracted extensive research interest in the scientific community....
Reactive oxygen species (ROS)-involved tumor therapeutic strategy, chemodynamic therapy (CDT), has attracted extensive research interest in the scientific community. However, the therapeutic effect of CDT is insufficient and unsustainable owing to the limited endogenous H O level in the tumor microenvironment. Here, peroxidase (POD)-like RuTe nanozyme with the immobilization of glucose oxidase (GOx) and allochroic 3,3',5,5'-tetramethylbenzidine (TMB) molecule have been synthesized to construct RuTe -GOx-TMB nanoreactors (RGT NRs) as cascade reaction systems for tumor-specific and self-replenishing cancer therapy. GOx in sequential nanocatalysts can effectively deplete glucose in tumor cells. Meanwhile, a sustainable supply of H O for subsequent Fenton-like reactions catalyzed by RuTe nanozyme is achieved in response to the mild acidic tumor microenvironment. Through this cascade reaction, highly toxic hydroxyl radicals (·OH) are produced, which can further oxidize TMB to trigger tumor-specific "turn-on" photothermal therapy (PTT). In addition, PTT and massive ROS can stimulate the tumor immune microenvironment and activate the systematic anti-tumor immune responses, exerting a notable effect on hindering tumor recurrence and metastasis. This study paves a promising paradigm for synergistic starvation therapy, PTT, and CDT cancer therapy with high efficiency.
Topics: Humans; Reactive Oxygen Species; Neoplasms; Glucose; Glucose Oxidase; Peroxidase; Tumor Microenvironment; Hydrogen Peroxide; Cell Line, Tumor
PubMed: 37285596
DOI: 10.1002/adhm.202300516 -
ACS Applied Bio Materials Feb 2024In biosensor development, silk fibroin is advantageous for providing transparent, flexible, chemically/mechanically stable, biocompatible, and sustainable substrates,...
In biosensor development, silk fibroin is advantageous for providing transparent, flexible, chemically/mechanically stable, biocompatible, and sustainable substrates, where the biorecognition element remains functional for long time periods. These properties are employed here in the production of point-of-care biosensors for resource-limited regions, which are able to display glucose levels without the need for external instrumentation. These biosensors are produced by photopatterning silk films doped with the enzymes glucose oxidase and peroxidase and photoelectrochromic molecules from the dithienylethene family acting as colorimetric mediators of the enzymatic reaction. The photopatterning results from the photoisomerization of dithienylethene molecules in the silk film from its initial uncolored opened form to its pink closed one. The photoisomerization is dose-dependent, and colored patterns with increasing color intensities are obtained by increasing either the irradiation time or the light intensity. In the presence of glucose, the enzymatic cascade reaction is activated, and peroxidase selectively returns closed dithienylethene molecules to their initial uncolored state. Color disappearance in the silk film is proportional to glucose concentration and used to distinguish between hypoglycemic (below 4 mM), normoglycemic (4-6 mM), and hyperglycemic levels (above 6 mM) by visual inspection. After the measurement, the biosensor can be regenerated by irradiation with UV light, enabling up to five measurement cycles. The coupling of peroxidase activity to other oxidoreductases opens the possibility to produce long-life reusable smart biosensors for other analytes such as lactate, cholesterol, or ethanol.
Topics: Silk; Colorimetry; Peroxidases; Biosensing Techniques; Peroxidase; Glucose
PubMed: 38270977
DOI: 10.1021/acsabm.3c00872