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1.
BMC Genom Data ; 25(1): 41, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711007

RESUMO

BACKGROUND: Class III peroxidase (POD) enzymes play vital roles in plant development, hormone signaling, and stress responses. Despite extensive research on POD families in various plant species, the knowledge regarding the POD family in Chinese pear (Pyrus bretschenedri) is notably limited. RESULTS: We systematically characterized 113 POD family genes, designated as PbPOD1 to PbPOD113 based on their chromosomal locations. Phylogenetic analysis categorized these genes into seven distinct subfamilies (I to VII). The segmental duplication events were identified as a prevalent mechanism driving the expansion of the POD gene family. Microsynteny analysis, involving comparisons with Pyrus bretschenedri, Fragaria vesca, Prunus avium, Prunus mume and Prunus persica, highlighted the conservation of duplicated POD regions and their persistence through purifying selection during the evolutionary process. The expression patterns of PbPOD genes were performed across various plant organs and diverse fruit development stages using transcriptomic data. Furthermore, we identified stress-related cis-acting elements within the promoters of PbPOD genes, underscoring their involvement in hormonal and environmental stress responses. Notably, qRT-PCR analyses revealed distinctive expression patterns of PbPOD genes in response to melatonin (MEL), salicylic acid (SA), abscisic acid (ABA), and methyl jasmonate (MeJA), reflecting their responsiveness to abiotic stress and their role in fruit growth and development. CONCLUSIONS: In this study, we investigated the potential functions and evolutionary dynamics of PbPOD genes in Pyrus bretschenedri, positioning them as promising candidates for further research and valuable indicators for enhancing fruit quality through molecular breeding strategies.


Assuntos
Regulação da Expressão Gênica de Plantas , Filogenia , Reguladores de Crescimento de Plantas , Pyrus , Pyrus/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Melatonina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oxilipinas/farmacologia , Ciclopentanos/farmacologia , Peroxidase/genética , Peroxidase/metabolismo , Acetatos/farmacologia , Acetatos/metabolismo , Frutas/genética , Frutas/crescimento & desenvolvimento
2.
Mikrochim Acta ; 191(6): 331, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38744722

RESUMO

A broad host range phage-based nanozyme (Fe-MOF@SalmpYZU47) was prepared for colorimetric detection of multiple Salmonella enterica strains. The isolation of a broad host range phage (SalmpYZU47) capable of infecting multiple S. enterica strains was achieved. Then, it was directly immobilized onto the Fe-MOF to prepare Fe-MOF@SalmpYZU47, exhibiting peroxidase-like activity. The peroxidase-like activity can be specifically inhibited by multiple S. enterica strains, benefiting from the broad host range capture ability of Fe-MOF@SalmpYZU47. Based on it, a colorimetric detection approach was developed for S. enterica in the range from 1.0 × 102 to 1.0 × 108 CFU mL-1, achieving a low limit of detection (LOD) of 11 CFU mL-1. The Fe-MOF@SalmpYZU47 was utilized for detecting S. enterica in authentic food samples, achieving recoveries ranging from 91.88 to 105.34%. Hence, our proposed broad host range phage-based nanozyme exhibits significant potential for application in the colorimetric detection of pathogenic bacteria.


Assuntos
Colorimetria , Limite de Detecção , Estruturas Metalorgânicas , Salmonella enterica , Colorimetria/métodos , Salmonella enterica/isolamento & purificação , Salmonella enterica/química , Estruturas Metalorgânicas/química , Microbiologia de Alimentos/métodos , Contaminação de Alimentos/análise , Peroxidase/química
3.
J Immunol Res ; 2024: 4283928, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699219

RESUMO

Objective: To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/µl) (GPA HE) to develop a differentiating strategy. Methods: A retrospective analysis of the POLVAS registry. Results: The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/µl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Conclusion: Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos , Eosinofilia , Sistema de Registros , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Estudos Retrospectivos , Eosinofilia/diagnóstico , Eosinofilia/imunologia , Eosinofilia/sangue , Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/imunologia , Idoso , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/imunologia , Síndrome de Churg-Strauss/epidemiologia , Peroxidase/imunologia , Eosinófilos/imunologia
4.
Front Immunol ; 15: 1360700, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736886

RESUMO

Introduction: Myocardial infarction (MI) is a significant contributor to morbidity and mortality worldwide. Many individuals who survive the acute event continue to experience heart failure (HF), with inflammatory and healing processes post-MI playing a pivotal role. Polymorphonuclear neutrophils (PMN) and monocytes infiltrate the infarcted area, where PMN release high amounts of the heme enzyme myeloperoxidase (MPO). MPO has numerous inflammatory properties and MPO plasma levels are correlated with prognosis and severity of MI. While studies have focused on MPO inhibition and controlling PMN infiltration into the infarcted tissue, less is known on MPO's role in monocyte function. Methods and results: Here, we combined human data with mouse and cell studies to examine the role of MPO on monocyte activation and migration. We revealed a correlation between plasma MPO levels and monocyte activation in a patient study. Using a mouse model of MI, we demonstrated that MPO deficiency led to an increase in splenic monocytes and a decrease in cardiac monocytes compared to wildtype mice (WT). In vitro studies further showed that MPO induces monocyte migration, with upregulation of the chemokine receptor CCR2 and upregulation of inflammatory pathways identified as underlying mechanisms. Conclusion: Taken together, we identify MPO as a pro-inflammatory mediator of splenic monocyte recruitment and activation post-MI and provide mechanistic insight for novel therapeutic strategies after ischemic injury.


Assuntos
Monócitos , Infarto do Miocárdio , Peroxidase , Animais , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/metabolismo , Peroxidase/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Humanos , Camundongos , Masculino , Movimento Celular , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Feminino , Neutrófilos/imunologia , Neutrófilos/metabolismo , Camundongos Knockout , Receptores CCR2/metabolismo , Pessoa de Meia-Idade
5.
ACS Nano ; 18(19): 12367-12376, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38695521

RESUMO

Bimetallic nanoparticles (NPs) with peroxidase-like (POD-like) activity play a crucial role in biosensing, disease treatment, environmental management, and other fields. However, their development is impeded by a vast range of tunable properties in components and structures, making the establishment of structure-effect relationships and the discovery of active materials challenging. Addressing this, we established robust scaling relationships by meticulously analyzing the catalytic reaction networks of pure metal NPs, which laid the volcano-shaped correlation between the activity and O* adsorption energy. Utilizing these relationships, we introduced an innovative and versatile descriptor of the NPs, which was then integrated into a machine learning-accelerated high-throughput computational workflow, significantly boosting the predictive accuracy for the POD-like activity of bimetallic NPs. Our methodological approach enabled the successful prediction of activities for 1260 bimetallic NPs, leading to the identification of several highly effective catalysts. Furthermore, we distilled several strategies for designing efficient bimetallic NPs based on our screening results.


Assuntos
Aprendizado de Máquina , Nanopartículas Metálicas , Nanopartículas Metálicas/química , Catálise , Peroxidase/química , Peroxidase/metabolismo , Ensaios de Triagem em Larga Escala/métodos
6.
Arch Biochem Biophys ; 756: 110023, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38705227

RESUMO

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.


Assuntos
Peroxidase , Staphylococcus aureus , Staphylococcus aureus/enzimologia , Humanos , Peroxidase/química , Peroxidase/metabolismo , Peroxidase/antagonistas & inibidores , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Domínios Proteicos , Sequência de Aminoácidos , Mutagênese Sítio-Dirigida , Modelos Moleculares , Conformação Proteica em alfa-Hélice
7.
Free Radic Biol Med ; 219: 104-111, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38608822

RESUMO

Hypothiocyanous acid (HOSCN) is an endogenous oxidant produced by peroxidase oxidation of thiocyanate (SCN-), an ubiquitous sulfur-containing pseudohalide synthesized from cyanide. HOSCN serves as a potent microbicidal agent against pathogenic bacteria, viruses, and fungi, functioning through thiol-targeting mechanisms, independent of currently approved antimicrobials. Additionally, SCN- reacts with hypochlorous acid (HOCl), a highly reactive oxidant produced by myeloperoxidase (MPO) at sites of inflammation, also producing HOSCN. This imparts both antioxidant and antimicrobial potential to SCN-. In this review, we discuss roles of HOSCN/SCN- in immunity and potential therapeutic implications for combating infections.


Assuntos
Tiocianatos , Tiocianatos/uso terapêutico , Tiocianatos/química , Tiocianatos/farmacologia , Tiocianatos/metabolismo , Humanos , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Peroxidase/metabolismo , Oxirredução , Ácido Hipocloroso/metabolismo , Ácido Hipocloroso/uso terapêutico , Ácido Hipocloroso/química , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia
8.
Mol Immunol ; 170: 26-34, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38603988

RESUMO

Neutrophils represent an important asset of innate immunity. Neutrophils express myeloperoxidase (MPO) which is a heme-containing peroxidase involved in microbial killing. In this study, by using real-time quantitative PCR and Western blot analysis, the flounder MPO (PoMPO) was observed to be highly expressed in the head kidney, followed by spleen, gill, and intestine during ontogeny - during developmental stages from larvae to adults. Furthermore, PoMPO positive cells were present in major immune organs of flounder at all developmental stages, and the number of neutrophils was generally higher as the fish grew to a juvenile stage. In addition, flow cytometry analysis revealed that the proportion of PoMPO positive cells relative to leukocytes, in the peritoneal cavity, head kidney, and peripheral blood of flounder juvenile stage was 18.3 %, 34.8 %, and 6.0 %, respectively, which is similar to the adult stage in flounder as previously reported. The presence and tissue distribution of PoMPO during ontogeny suggests that PoMPO positive cells are indeed a player of the innate immunity at all developmental stages of flounder.


Assuntos
Linguado , Imunidade Inata , Neutrófilos , Peroxidase , Animais , Linguado/imunologia , Peroxidase/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Imunidade Inata/imunologia , Brânquias/imunologia , Rim Cefálico/imunologia , Proteínas de Peixes/metabolismo , Proteínas de Peixes/imunologia , Proteínas de Peixes/genética , Citometria de Fluxo , Baço/imunologia
9.
RMD Open ; 10(2)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688691

RESUMO

OBJECTIVES: To describe clinical and laboratory characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and thyroid disease (TD). We also aimed to calculate incidence and identify predictors of TD in two large cohorts of patients with AAV. METHODS: The study comprised 644 patients with AAV in a population-based cohort from southern Sweden (n=325) and a cohort from a specialised vasculitis centre in Cambridge, UK (n=319). Diagnosis and classification of AAV and TD were confirmed by medical record review. Person-years (PY) of follow-up were calculated from AAV diagnosis to the earliest of TD, death or the end of study. Cox-regression analysis was employed to study predictors of TD. RESULTS: At AAV diagnosis, 100 individuals (15.5%, 77 females) had TD, 59 had myeloperoxidase (MPO)-ANCA+ and 34 had proteinase-3 (PR3)-ANCA+. Patients with TD tended to have lower C reactive protein, lower haemoglobin and fewer constitutional symptoms. Survival and renal survival was greater in those patients with AAV with pre-existing TD. During 4522 PY of follow-up, a further 29 subjects developed TD, yielding an incidence rate of 641/100 000 PY. No analysed factor predicted de novo TD in AAV. The prevalence of TD among patients with AAV in southern Sweden was 18%. CONCLUSION: TD is a common comorbidity in AAV, affecting nearly one in five. While TD diagnosis is more common in females and MPO-ANCA+, these factors do not predict de novo TD after initiation of AAV treatment, necessitating monitoring of all patients with AAV with respect to this comorbidity.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Doenças da Glândula Tireoide , Humanos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Doenças da Glândula Tireoide/epidemiologia , Idoso , Suécia/epidemiologia , Incidência , Anticorpos Anticitoplasma de Neutrófilos/sangue , Peroxidase/imunologia , Adulto , Fatores de Risco , Biomarcadores/sangue , Mieloblastina/imunologia
10.
Int J Biol Macromol ; 267(Pt 2): 131477, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38604430

RESUMO

Salt stress severely limits the growth and yield of wheat in saline-alkali soil. While nanozymes have shown promise in mitigating abiotic stress by scavenging reactive oxygen species (ROS) in plants, their application in alleviating salt stress for wheat is still limited. This study synthesized a highly active nanozyme catalyst known as ZnPB (Zn-modified Prussian blue) to improve the yield and quality of wheat in saline soil. According to the Michaelis-Menten equation, ZnPB demonstrates exceptional peroxidase-like enzymatic activity, thereby mitigating oxidative damage caused by salt stress. Additionally, studies have shown that the ZnPB nanozyme is capable of regulating intracellular Na+ efflux and K+ retention in wheat, resulting in a decrease in proline and soluble protein levels while maintaining the integrity of macromolecules within the cell. Consequently, field experiments demonstrated that the ZnPB nanozyme increased winter wheat yield by 12.15 %, while also significantly enhancing its nutritional quality. This research offers a promising approach to improving the salinity tolerance of wheat, while also providing insights into its practical application.


Assuntos
Ferrocianetos , Tolerância ao Sal , Sementes , Triticum , Zinco , Triticum/efeitos dos fármacos , Ferrocianetos/química , Zinco/química , Zinco/farmacologia , Tolerância ao Sal/efeitos dos fármacos , Sementes/efeitos dos fármacos , Peroxidase/metabolismo , Sódio/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
Biochemistry (Mosc) ; 89(Suppl 1): S90-S111, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38621746

RESUMO

Reactive halogen species (RHS) are highly reactive compounds that are normally required for regulation of immune response, inflammatory reactions, enzyme function, etc. At the same time, hyperproduction of highly reactive compounds leads to the development of various socially significant diseases - asthma, pulmonary hypertension, oncological and neurodegenerative diseases, retinopathy, and many others. The main sources of (pseudo)hypohalous acids are enzymes from the family of heme peroxidases - myeloperoxidase, lactoperoxidase, eosinophil peroxidase, and thyroid peroxidase. Main targets of these compounds are proteins and peptides, primarily methionine and cysteine residues. Due to the short lifetime, detection of RHS can be difficult. The most common approach is detection of myeloperoxidase, which is thought to reflect the amount of RHS produced, but these methods are indirect, and the results are often contradictory. The most promising approaches seem to be those that provide direct registration of highly reactive compounds themselves or products of their interaction with components of living cells, such as fluorescent dyes. However, even such methods have a number of limitations and can often be applied mainly for in vitro studies with cell culture. Detection of reactive halogen species in living organisms in real time is a particularly acute issue. The present review is devoted to RHS, their characteristics, chemical properties, peculiarities of interaction with components of living cells, and methods of their detection in living systems. Special attention is paid to the genetically encoded tools, which have been introduced recently and allow avoiding a number of difficulties when working with living systems.


Assuntos
Halogênios , Peroxidases , Peroxidases/metabolismo , Halogênios/metabolismo , Peroxidase/metabolismo , Peroxidase de Eosinófilo , Antioxidantes
12.
Int J Mol Sci ; 25(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674081

RESUMO

Marrubiin is a diterpene with a long history of a wide range of biological activities. In this study, the anti-inflammatory effects of marrubiin were investigated using several in vitro and in vivo assays. Marrubiin inhibited carrageenan-induced peritoneal inflammation by preventing inflammatory cell infiltration and peritoneal mast cell degranulation. The anti-inflammatory activity was further demonstrated by monitoring a set of biochemical parameters, showing that the peritoneal fluid of animals treated with marrubiin had lower levels of proteins and lower myeloperoxidase activity compared with the fluid of animals that were not treated. Marrubiin exerted the most pronounced cytotoxic activity towards peripheral mononuclear cells, being the main contributors to peritoneal inflammation. Additionally, a moderate lipoxygenase inhibition activity of marrubiin was observed.


Assuntos
Anti-Inflamatórios , Carragenina , Diterpenos , Mastócitos , Animais , Carragenina/efeitos adversos , Camundongos , Diterpenos/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos C57BL , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Peritonite/metabolismo , Peritonite/patologia , Masculino , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/patologia , Degranulação Celular/efeitos dos fármacos , Peroxidase/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo
13.
Dev Comp Immunol ; 156: 105180, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38641186

RESUMO

Isoprostanes (isoP) are formed during conditions of oxidative stress (OS) through the oxidation of cell membrane fatty acids. Different classes of isoP are formed depending on the fatty acid being oxidized but the biological activity of these molecules in innate immune cells is poorly understood. Thus, the objective of this study was to compare in vitro the effects of F2- and F3-isoP on neutrophil microbicidal functions. We isolated neutrophils from 6 dairy cows and incubated them for 8 h at various concentrations of F2- and F3-isoP. Then, microbicidal function was assessed in terms of phagocytosis, respiratory burst, myeloperoxidase activity, and extracellular trap formation. In vitro supplementation with F3-isoP enhanced microbicidal capabilities whereas supplementation with F2-isoP decreased or did not impact these microbe killing functions. Hence, favoring the production of F3- over F2-isoprostanes may be a strategy to augment neutrophils' functional capacity during OS conditions. This should be tested in vivo.


Assuntos
Armadilhas Extracelulares , F2-Isoprostanos , Neutrófilos , Estresse Oxidativo , Peroxidase , Fagocitose , Explosão Respiratória , Animais , Neutrófilos/imunologia , Bovinos , F2-Isoprostanos/metabolismo , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Peroxidase/metabolismo , Células Cultivadas , Feminino , Imunidade Inata , Oxirredução
14.
Lancet Rheumatol ; 6(5): e300-e313, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574743

RESUMO

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.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Peroxidase , Humanos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Peroxidase/imunologia
15.
Anal Chem ; 96(19): 7661-7668, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38687969

RESUMO

The development of sensitive, selective, and rapid methods to detect bacteria in complex media is essential to ensuring human health. Virulence factors, particularly pore-forming toxins (PFTs) secreted by pathogenic bacteria, play a crucial role in bacterial diseases and serve as indicators of disease severity. In this study, a nanochannel-based label-free electrochemical sensing platform was developed for the detection of specific pathogenic bacteria based on their secreted PFTs. In this design, wood substrate channels were functionalized with a Fe-based metal-organic framework (FeMOF) and then protected with a layer of phosphatidylcholine (PC)-based phospholipid membrane (PM) that serves as a peroxidase mimetic and a channel gatekeeper, respectively. Using Staphylococcus aureus (S. aureus) as the model bacteria, the PC-specific PFTs secreted by S. aureus perforate the PM layer. Now exposed to the FeMOF, uncharged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) molecules in the electrolyte undergo oxidation to cationic products (ABTS•+). The measured transmembrane ionic current indicates the presence of S. aureus and methicillin-resistant S. aureus (MRSA) with a low detection limit of 3 cfu mL-1. Besides excellent specificity, this sensing approach exhibits satisfactory performance for the detection of target bacteria in the complex media of food.


Assuntos
Técnicas Eletroquímicas , Staphylococcus aureus , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/metabolismo , Estruturas Metalorgânicas/química , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Peroxidase/metabolismo , Peroxidase/química , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/análise , Técnicas Biossensoriais
16.
Anal Methods ; 16(16): 2606-2613, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38618990

RESUMO

2,6-Pyridinedicarboxylic acid (DPA) is a significant biomarker of anthrax, which is a deadly infectious disease for human beings. However, the development of a convenient anthrax detection method is still a challenge. Herein, we report a novel europium metal-organic framework (Eu-MOF) with an enhanced peroxidase-like activity and fluorescence property for DPA detection. The Eu-MOF was one-step synthesized using Eu3+ ions and 2-methylimidazole. In the presence of DPA, the intrinsic fluorescence of Eu3+ ions is sensitized, the fluorescence intensity linearly increases with an increase in DPA concentration, and the fluorescence color changes from blue to purple. Simultaneously, the peroxide-like activity of the Eu-MOF is enhanced by DPA, which can promote the oxidation of TMB to oxTMB. The absorbance values increase linearly with DPA concentrations, and the colorimetric images change from colorless to blue. The dual-mode detection of DPA has good sensitivity with a colorimetric detection limit of 0.67 µM and a fluorescent detection limit of 16.67 nM. Moreover, a simple detection method for DPA was developed using a smartphone with the RGB analysis system. A portable kit with standard color cards was developed using paper test strips. The proposed methods have good practicability for DPA detection in real samples. In conclusion, the developed Eu-MOF biosensor offers a valuable and general platform for anthrax diagnosis.


Assuntos
Colorimetria , Európio , Estruturas Metalorgânicas , Ácidos Picolínicos , Európio/química , Estruturas Metalorgânicas/química , Colorimetria/métodos , Ácidos Picolínicos/análise , Ácidos Picolínicos/química , Limite de Detecção , Humanos , Fluorescência , Antraz/diagnóstico , Smartphone , Espectrometria de Fluorescência/métodos , Peroxidase/química , Peroxidase/metabolismo
17.
J Am Chem Soc ; 146(15): 10478-10488, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38578196

RESUMO

During biomedical applications, nanozymes, exhibiting enzyme-like characteristics, inevitably come into contact with biological fluids in living systems, leading to the formation of a protein corona on their surface. Although it is acknowledged that molecular adsorption can influence the catalytic activity of nanozymes, there is a dearth of understanding regarding the impact of the protein corona on nanozyme activity and its determinant factors. In order to address this gap, we employed the AuNR@Pt@PDDAC [PDDAC, poly(diallyldimethylammonium chloride)] nanorod (NR) as a model nanozyme with multiple activities, including peroxidase, oxidase, and catalase-mimetic activities, to investigate the inhibitory effects of the protein corona on the catalytic activity. After the identification of major components in the plasma protein corona on the NR, we observed that spherical proteins and fibrous proteins induced distinct inhibitory effects on the catalytic activity of nanozymes. To elucidate the underlying mechanism, we uncovered that the adsorbed proteins assembled on the surface of the nanozymes, forming protein networks (PNs). Notably, the PNs derived from fibrous proteins exhibited a screen mesh-like structure with smaller pore sizes compared to those formed by spherical proteins. This structural disparity resulted in a reduced efficiency for the permeation of substrate molecules, leading to a more robust inhibition in activity. These findings underscore the significance of the protein shape as a crucial factor influencing nanozyme activity. This revelation provides valuable insights for the rational design and application of nanozymes in the biomedical fields.


Assuntos
Nanoestruturas , Coroa de Proteína , Escleroproteínas , Peroxidase , Adsorção , Corantes , Catálise
18.
Physiol Plant ; 176(2): e14294, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38634335

RESUMO

In our comprehensive meta-analysis, we initially collected 177 publications focusing on the impact of melatonin on wheat. After meticulous screening, 40 published studies were selected, encompassing 558 observations for antioxidant enzymes, 312 for reactive oxygen species (ROS), and 92 for soluble biomolecules (soluble sugar and protein). This analysis revealed significant heterogeneity across studies (I2 > 99% for enzymes, ROS, and soluble biomolecules) and notable publication bias, indicating the complexity and variability in the research field. Melatonin application generally increased antioxidant enzyme activities [superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX)] in wheat, particularly under stress conditions, such as high temperature and heavy-metal exposure. Compared to control, melatonin application increased SOD, POD, CAT, and APX activities by 29.5, 16.96, 35.98, and 171.64%, respectively. Moreover, oxidative stress markers like hydrogen peroxide (H2O2), superoxide anion (O2), and malondialdehyde (MDA) decreased with melatonin by 23.73, 13.64, and 21.91%, respectively, suggesting a reduction in oxidative stress. The analysis also highlighted melatonin's role in improving carbohydrate metabolism and antioxidant defenses. Melatonin showed an overall increase of 12.77% in soluble sugar content, and 22.76% in glutathione peroxidase (GPX) activity compared to the control. However, the effects varied across different wheat varieties, environmental conditions, and application methods. Our study also uncovered complex relationships between antioxidant enzyme activities and H2O2 levels, indicating a nuanced regulatory role of melatonin in oxidative stress responses. Our meta-analysis demonstrates the significant role of melatonin in increasing wheat resilience to abiotic stressors, potentially through its regulatory impact on antioxidant defense systems and stress response.


Assuntos
Antioxidantes , Melatonina , Antioxidantes/metabolismo , Melatonina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Triticum/metabolismo , Peróxido de Hidrogênio/metabolismo , Catalase/metabolismo , Superóxido Dismutase/metabolismo , Peroxidases/metabolismo , Peroxidase/metabolismo , Estresse Oxidativo , Açúcares/metabolismo , Malondialdeído/metabolismo
19.
Biosens Bioelectron ; 255: 116259, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38574559

RESUMO

Carbon-based nanozymes possessing peroxidase-like activity have attracted significant interest because of their potential to replace native peroxidases in biotechnology. Although various carbon-based nanozymes have been developed, their relatively low catalytic efficiency needs to be overcome to realize their practical utilization. Here, inspired by the elemental uniqueness of Cu and the doped elements N and S, as well as the active site structure of Cu-centered oxidoreductases, we developed a new carbon-based peroxidase-mimicking nanozyme, single-atom Cu-centered N- and S-codoped reduced graphene oxide (Cu-NS-rGO), which preserved many Cu-N4 and Cu-N4S active sites and showed dramatically high peroxidase-like activity without any oxidase-like activity, yielding up to 2500-fold higher catalytic efficiency (kcat/Km) than that of pristine rGO. The high catalytic activity of Cu-NS-rGO might be attributed to the acceleration of electron transfer from Cu single atom as well as synergistic effects from both Cu-N4 and Cu-N4S active sites, which was theoretically confirmed by Gibbs free energy calculations using density functional theory. The prepared Cu-NS-rGO was then used to construct an electrochemical bioassay system for detecting choline and acetylcholine by coupling with the corresponding oxidases. Using this system, both target molecules were selectively determined with high sensitivity that was sufficient to clinically determine their levels in physiological fluids. Overall, this study will facilitate the development of nanocarbon-based nanozymes and their electrochemical biosensing applications, which can be extended to the development of miniaturized devices in point-of-care testing environments.


Assuntos
Técnicas Biossensoriais , Grafite , Peroxidase , Peroxidase/química , Domínio Catalítico , Peroxidases/química , Oxirredutases , Carbono/química
20.
Biosens Bioelectron ; 255: 116271, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38583355

RESUMO

The metal-organic frameworks (MOFs) nanozyme-mediated paper-based analytical devices (PADs) have shown great potential in portable visual determination of phenolic compounds in the environment. However, most MOF nanozymes suffer from poor dispersibility and block-like structure, which often prompts deposition and results in diminished enzymatic activity, severely hindering their environmental applications. Here, we proposed colorimetric PADs for the visual detection of dichlorophen (Dcp) based on its significant inhibitory effect on the two-dimensional (2D) MOF nanozyme activity. Specifically, we synthesized a 2D Cu TCPP (Fe) (defined as 2D-CTF) MOF nanozyme exhibiting excellent dispersibility and remarkable peroxidase-like (POD-like) activity, which could catalyze the oxidation and subsequent color change of 3,3',5,5'-tetramethylbenzidine even under neutral conditions. Notably, the POD-like activity of 2D-CTF demonstrated a unique response to Dcp because of the occupation of Fe-N4 active sites on the 2D-CTF. This property enables the use of 2D-CTF as a highly efficient catalyst to develop colorimetric PADs for naked-eye and portable detection of Dcp. We believe that the proposed colorimetric PADs offer an efficient method for Dcp assay and open fresh avenues for the advancement of colorimetric sensors for analyzing of phenolic toxic substances in real samples.


Assuntos
Técnicas Biossensoriais , Diclorofeno , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Técnicas Biossensoriais/métodos , Peroxidases/química , Peroxidase , Colorimetria/métodos , Fenóis , Peróxido de Hidrogênio/química
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