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Journal of Cellular and Molecular... Jul 2023Trauma represents one of the leading causes of death worldwide. Traumatic injuries elicit a dynamic inflammatory response with systemic release of inflammatory...
Trauma represents one of the leading causes of death worldwide. Traumatic injuries elicit a dynamic inflammatory response with systemic release of inflammatory cytokines. Disbalance of this response can lead to systemic inflammatory response syndrome or compensatory anti-inflammatory response syndrome. As neutrophils play a major role in innate immune defence and are crucial in the injury-induced immunological response, we aimed to investigate systemic neutrophil-derived immunomodulators in trauma patients. Therefore, serum levels of neutrophil elastase (NE), myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) were quantified in patients with injury severity scores above 15. Additionally, leukocyte, platelet, fibrinogen and CRP levels were assessed. Lastly, we analysed the association of neutrophil-derived factors with clinical severity scoring systems. Although the release of MPO, NE and CitH3 was not predictive of mortality, we found a remarkable increase in MPO and NE in trauma patients as compared with healthy controls. We also found significantly increased levels of MPO and NE on Days 1 and 5 after initial trauma in critically injured patients. Taken together, our data suggest a role for neutrophil activation in trauma. Targeting exacerbated neutrophil activation might represent a new therapeutic option for critically injured patients.
Topics: Humans; Neutrophils; Histones; Cytokines; Neutrophil Activation; Multiple Trauma; Peroxidase
PubMed: 37328954
DOI: 10.1111/jcmm.17786 -
Annals of the Rheumatic Diseases Mar 2024Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are life-threatening systemic autoimmune diseases manifesting in the kidneys as necrotizing...
OBJECTIVES
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are life-threatening systemic autoimmune diseases manifesting in the kidneys as necrotizing crescentic glomerulonephritis (NCGN). ANCA antigens are myeloperoxidase (MPO) or proteinase 3. Current treatments include steroids, cytotoxic drugs and B cell-depleting antibodies. The use of chimeric antigen receptor (CAR) T cells in autoimmune diseases is a promising new therapeutic approach. We tested the hypothesis that CAR T cells targeting CD19 deplete B cells, including MPO-ANCA-producing B cells, thereby protecting from ANCA-induced NCGN.
METHODS
We tested this hypothesis in a preclinical MPO-AAV mouse model. NCGN was established by immunisation of MPO mice with murine MPO, followed by irradiation and transplantation with haematopoietic cells from wild-type mice alone or together with either CD19-targeting CAR T cells or control CAR T cells.
RESULTS
CD19 CAR T cells efficiently migrated to and persisted in bone marrow, spleen, peripheral blood and kidneys for up to 8 weeks. CD19 CAR T cells, but not control CAR T cells, depleted B cells and plasmablasts, enhanced the MPO-ANCA decline, and most importantly protected from NCGN.
CONCLUSION
Our proof-of-principle study may encourage further exploration of CAR T cells as a treatment for ANCA-vasculitis patients with the goal of drug-free remission.
Topics: Humans; Mice; Animals; Antibodies, Antineutrophil Cytoplasmic; Glomerulonephritis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Acute Kidney Injury; T-Lymphocytes; Peroxidase
PubMed: 38182404
DOI: 10.1136/ard-2023-224875 -
International Journal of Molecular... Dec 2023Recent years have brought progress in understanding the role of the neutrophil, dispelling the dogma of homogeneous cells mainly involved in the prime defence against... (Review)
Review
Recent years have brought progress in understanding the role of the neutrophil, dispelling the dogma of homogeneous cells mainly involved in the prime defence against pathogens, shedding light on their pathogenic role in inflammatory diseases and on the importance of antineutrophil-cytoplasmic antibodies' pathogenic role in ANCA-associated vasculitides vasculitis (AAV). Myeloperoxidase (MPO) and proteinase 3 (PR3) expressed in neutrophil granulocytes are the most common targets for ANCAs and contribute to the formation of MPO-ANCAs and PR3-ANCAs which, released to the bloodstream, become an excellent diagnostic tool for AAV. In this study, we focus on increasing the clinical and experimental evidence that supports the pathogenic role of ANCAs in AAV. Additionally, we discuss the diagnostic utility of ANCAs for disease activity and prognosis in AAV. Understanding the central role of ANCAs in AAV is crucial for advancing our knowledge of these complex disorders and developing targeted therapeutic strategies in the era of personalized medicine.
Topics: Humans; Autoantibodies; Neutrophils; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Peroxidase; Myeloblastin
PubMed: 38139045
DOI: 10.3390/ijms242417217 -
Plant Physiology Aug 2023Drought and flooding are the two most important environmental factors limiting maize (Zea mays L.) production globally. This study aimed to investigate the physiological...
Drought and flooding are the two most important environmental factors limiting maize (Zea mays L.) production globally. This study aimed to investigate the physiological mechanisms and accurate evaluation indicators and methods of maize germplasm involved in drought and flooding stresses. The twice replicated pot experiments with 60 varieties, combined with the field validation experiment with 3 varieties, were conducted under well-watered, drought, and flooding conditions. Most varieties exhibited stronger tolerance to drought than flooding due to higher antioxidant enzyme activities, osmotic adjustment substances, and lower reactive oxygen species. In contrast, flooding stress resulted in higher levels of reactive oxygen species (particularly O2-), ascorbate peroxidase, catalase, peroxidase, and soluble sugars but lower levels of superoxide dismutase, proline, and soluble protein compared with well-watered conditions. Superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, proline, soluble sugars, and protein contents, in addition to plant height, leaf area/plant, and stem diameter, were accurate and representative indicators for evaluating maize tolerance to drought and flooding stresses and could determine a relatively high mean forecast accuracy of 100.0% for the comprehensive evaluation value. A total of 4 principal components were extracted, in which different principal components played a vital role in resisting different water stresses. Finally, the accuracy of the 3 varieties screened by multivariate analysis was verified in the field. This study provides insights into the different physiological mechanisms and accurate evaluation methods of maize germplasm involved in drought and flooding stresses, which could be valuable for further research and breeding.
Topics: Catalase; Zea mays; Reactive Oxygen Species; Ascorbate Peroxidases; Droughts; Stress, Physiological; Plant Breeding; Antioxidants; Peroxidases; Peroxidase; Superoxide Dismutase; Water; Proline; Multivariate Analysis; Sugars
PubMed: 37249039
DOI: 10.1093/plphys/kiad317 -
Small (Weinheim An Der Bergstrasse,... Aug 2023Realizing high-precise and adjustable regulation of engineering nanozyme is important in nanotechnology. Here, Ag@Pt nanozymes with excellent peroxidase-like and...
Realizing high-precise and adjustable regulation of engineering nanozyme is important in nanotechnology. Here, Ag@Pt nanozymes with excellent peroxidase-like and antibacterial effects are designed and synthesized by nucleic acid and metal ions coordination-driven one-step rapid self-assembly. The adjustable NA-Ag@Pt nanozyme is synthesized within 4 min using single-stranded nucleic acid as templates, and peroxidase-like enhancing FNA-Ag@Pt nanozyme is received by regulating functional nucleic acids (FNA) based on NA-Ag@Pt nanozyme. Both Ag@Pt nanozymes that are developed not only has simple and general synthesis approaches, but also can produce artificial precise adjustment and possess dual-functional. Moreover, when lead ion-specific aptamers as FNA are introduced to NA-Ag@Pt nanozyme, the Pb aptasensor is successfully constructed by increasing electron conversion efficiency and improving the specificity of nanozyme. In addition, both nanozyme has good antibacterial properties, with ~100% and ~85% antibacterial efficiency against Escherichia coli and Staphylococcus aureus, respectively. This work provides a synthesis method of novelty dual-functional Ag@Pt nanozymes and successful application in metal ions detection and antibacterial agents.
Topics: Peroxidase; Peroxidases; Anti-Bacterial Agents; Nucleic Acids; Ions
PubMed: 37078838
DOI: 10.1002/smll.202301048 -
Chemosphere Jan 2024Single-atom nanozymes (SANs) are nanomaterials-based nanozymes with atomically dispersed enzyme-like active sites. SANs offer improved as well as tunable catalytic... (Review)
Review
Single-atom nanozymes (SANs) are nanomaterials-based nanozymes with atomically dispersed enzyme-like active sites. SANs offer improved as well as tunable catalytic activity. The creation of extremely effective SANs and their potential uses have piqued researchers' curiosity due to their advantages of cheap cost, variable catalytic activity, high stability, and large-scale production. Furthermore, SANs with uniformly distributed active centers and definite coordination structures offer a distinctive opportunity to investigate the structure-activity correlation and control the geometric and electrical features of metal centers. SANs have been extensively explored in photo-, thermal-, and electro-catalysis. However, SANs suffer from the following disadvantages, such as efficiency, non-mimicking of the 3-D complexity of natural enzymes, limited and narrow range of artificial SANs, and biosafety aspects. Among a quite limited range of artificial SANs, the peroxidase action of SANs has attracted significant research attention in the last five years with the aim of producing reactive oxygen species for use in cancer therapy, and water treatment among many other applications. In this review, we explore the recent progress of different SANs as peroxidase mimics, the role of the metal center in enzymatic activity, possible prospects, and underlying limitations in real-time applications.
Topics: Biomimetic Materials; Nanostructures; Peroxidase; Catalysis; Peroxidases
PubMed: 38303399
DOI: 10.1016/j.chemosphere.2023.140557 -
Acta Biomaterialia Sep 2023During the past few years, bacterial infection and oxidative stress have become important issues for wound healing. However, the emergence of numerous drug-resistant...
During the past few years, bacterial infection and oxidative stress have become important issues for wound healing. However, the emergence of numerous drug-resistant superbugs has had a serious impact on the treatment of infected wounds. Presently, the development of new nanomaterials has become one of the most important approaches to the treatment of drug-resistant bacterial infections. Herein, coordination polymer copper-gallic acid (Cu-GA) nanorods with multi-enzyme activity is successfully prepared for efficient wound treatment of bacterial infection, which can effectively promote wound healing. Cu-GA can be efficiently prepared by a simple solution method and had good physiological stability. Interestingly, Cu-GA shows enhanced multienzyme activity (peroxidase, glutathione peroxidase, and superoxide dismutase), which can produce a large number of reactive oxygen species (ROS) under acidic conditions while scavenging ROS under neutral conditions. In acidic environment, Cu-GA possesses POD (peroxidase)-like and glutathione peroxidase (GSH-Px)-like catalytic activities that is capable of killing bacteria; but in neutral environment, Cu-GA exhibits superoxide dismutase (SOD)-like catalytic activity that can scavenge ROS and promote wound healing. In vivo studies show that Cu-GA can promote wound infection healing and have good biosafety. Cu-GA contributes to the healing of infected wounds by inhibiting bacterial growth, scavenging reactive oxygen species, and promoting angiogenesis. STATEMENT OF SIGNIFICANCE: Cu-GA-coordinated polymer nanozymes with multienzyme activity were successfully prepared for efficient wound treatment of bacterial infection, which could effectively promote wound healing. Interestingly, Cu-GA exhibited enhanced multienzyme activity (peroxidase, glutathione peroxidase, and superoxide dismutase), which could produce a large number of reactive oxygen species (ROS) under acidic conditions and scavenge ROS under neutral conditions. In vitro and in vivo studies demonstrated that Cu-GA was capable of killing bacteria, controlling inflammation, and promoting angiogenesis.
Topics: Humans; Copper; Gallic Acid; Reactive Oxygen Species; Disinfection; Superoxide Dismutase; Wound Healing; Peroxidases; Peroxidase; Glutathione Peroxidase; Bacterial Infections; Anti-Bacterial Agents
PubMed: 37270076
DOI: 10.1016/j.actbio.2023.05.048 -
Rheumatology (Oxford, England) Sep 2023To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype.
OBJECTIVE
To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype.
METHODS
A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems.
RESULTS
rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619.
CONCLUSIONS
Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
Topics: Female; Humans; Male; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Myeloblastin; Peroxidase; Sex Characteristics
PubMed: 37004177
DOI: 10.1093/rheumatology/kead152 -
International Journal of Biological... Jul 2023Lignin modifying enzymes (LMEs) have gained widespread recognition in depolymerization of lignin polymers by oxidative cleavage. LMEs are a robust class of biocatalysts... (Review)
Review
Lignin modifying enzymes (LMEs) have gained widespread recognition in depolymerization of lignin polymers by oxidative cleavage. LMEs are a robust class of biocatalysts that include lignin peroxidase (LiP), manganese peroxidase (MnP), versatile peroxidase (VP), laccase (LAC), and dye-decolorizing peroxidase (DyP). Members of the LMEs family act on phenolic, non-phenolic substrates and have been widely researched for valorization of lignin, oxidative cleavage of xenobiotics and phenolics. LMEs implementation in the biotechnological and industrial sectors has sparked significant attention, although its potential future applications remain underexploited. To understand the mechanism of LMEs in sustainable pollution mitigation, several studies have been undertaken to assess the feasibility of LMEs in correlating to diverse pollutants for binding and intermolecular interactions at the molecular level. However, further investigation is required to fully comprehend the underlying mechanism. In this review we presented the key structural and functional features of LMEs, including the computational aspects, as well as the advanced applications in biotechnology and industrial research. Furthermore, concluding remarks and a look ahead, the use of LMEs coupled with computational framework, built upon artificial intelligence (AI) and machine learning (ML), has been emphasized as a recent milestone in environmental research.
Topics: Lignin; Artificial Intelligence; Peroxidases; Biotechnology; Laccase; Phenols
PubMed: 37217044
DOI: 10.1016/j.ijbiomac.2023.124968 -
Clinical Rheumatology Mar 2024Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) typically manifests as rapidly progressive glomerulonephritis with crescent formation. In this... (Review)
Review
Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) typically manifests as rapidly progressive glomerulonephritis with crescent formation. In this report, we present a local case of myeloperoxidase (MPO)-AAV-associated acute interstitial nephritis (AIN), showing slight pauci-immune glomerulonephritis and positive MPO-ANCA. This case is characterized by foot process effacement of podocytes in the glomerulus, a favorable prognosis, and an absence of crescentic formation. To further understand this condition, we conducted a comprehensive literature search on Google Scholar and PubMed, employing both free text words and MeSH terms related to "AAV and AIN." This search yielded 24 cases, which we analyzed for their clinical features, laboratory findings, renal pathological characteristics, and therapeutic outcomes. AAV-associated interstitial nephritis predominantly affects elderly patients and is often associated with anemia, proteinuria, hematuria, and nonspecific manifestations, including fever, anorexia, fatigue, edema, and weight loss. Most of the cases in our review were MPO-ANCA-positive and exhibited isolated interstitial inflammation. These patients typically presented with relatively lower levels of serum creatinine, 24-h urine protein levels, and MPO-ANCA titers. All patients in our study received immunosuppressive therapy, including glucocorticoids, immunosuppressants, and rituximab, with the majority achieving clinical remission. Isolated AIN in the context of AAV is a rare occurrence, but it displays distinct clinical, laboratory, and pathological features. Patients with this presentation show a positive response to immunosuppressive treatment. Nevertheless, the establishment of definitive therapy guidelines for AAV-associated AIN remains uncertain and necessitates further investigation to develop comprehensive treatment guidelines. AIN, particularly when lacking typical glomerulus lesions, may represent a novel subgroup within MPO-AAV warranting additional research and clinical attention. Key Points • This study contributes valuable scientific insights by highlighting that MPO-AAV-associated interstitial nephritis, even without crescentic formation, can exhibit podocyte foot process effacement and respond well to treatment. • The presence of AIN, independent of crescentic glomerulonephritis, suggests the potential emergence of a new subclass within MPA-AAV. • Notably, some cases of MPO-AAV-associated AIN may present with normal levels of Scr (Table 5, cases 5, 6, and 17). • This observation highlights the importance of considering renal biopsy, diagnosis, and therapy in a timely manner to prevent the development of chronic kidney disease (CKD).
Topics: Humans; Aged; Antibodies, Antineutrophil Cytoplasmic; Kidney; Glomerulonephritis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Nephritis, Interstitial; Immunosuppressive Agents; Peroxidase
PubMed: 37932622
DOI: 10.1007/s10067-023-06798-z