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1.
J Colloid Interface Sci ; 635: 481-493, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36599245

RESUMO

Nanomaterials-based enzyme mimics (nanozymes), by simulating enzyme catalysis, have shown potential in numerous biocatalytic applications, but nanozymes face significant challenges of catalytic activity and reusability that may restrict their practical uses. Herein, we report facile fabrication of surface-clean IrO2 clusters supported on dendritic mesoporous silica nanospheres (DMSNs), which exhibit superior peroxidase-like activity, high thermal/long-term stability, and good recyclability. The IrO2 clusters (1.4 ± 0.2 nm in size) are obtained by the laser ablation without any ligands and possess negative surface charge, which are efficiently loaded on the amino-functionalized DMSNs by electrostatic adsorption. Owing to morphological and structural advantages, the resulted DMSN/IrO2 heterostructure displays outstanding peroxidase-like catalytic performance. Compared with horseradish peroxidase, it shows comparable affinities but higher reaction rate (2.95 × 10-7 M·s-1) towards H2O2, resulting from rapid electron transfer during the catalysis. This value is also larger than those of mesoporous silicas supported metal or metal oxides nanoparticles/clusters in the previous studies. Benefitting from excellent peroxidase-catalysis of the DMSN/IrO2, the colorimetric assays are further successfully established for the detection of acetylcholine esterase and its inhibitor, showing high sensitivity and selectivity. The work provides novel design of supported nanozymes for biosensing.


Assuntos
Acetilcolinesterase , Nanosferas , Dióxido de Silício/química , Peróxido de Hidrogênio/química , Peroxidase/química , Peroxidases , Catálise , Colorimetria/métodos
2.
Anal Biochem ; 664: 115045, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36657510

RESUMO

Cascade reactions catalyzed by natural uricase and mimic peroxidase (MPOD) have been applied for uric acid (UA) detection. However, the optimal catalytic activity of MPOD is mostly in acidic conditions (pH 2-5), mismatching the optimal catalytic alkaline environment of uricase. In this paper, using CuSO4 and urea as raw materials, a MPOD with high catalytic activity in alkaline environment was synthesized by hydrothermal method. Then, based on coupling reaction of uricase/UA/MPOD/guaiacol (GA) system, a novel spectrophotometric method was established to detect 5-60 µmol/L UA (limit of detection = 3.14 µmol/L (S/N = 3)) and accurately quantified serum UA (275.6 ± 39.9 µmol/L, n = 5) with 95-105% of standard addition recovery. The results were consistent with commercial UA kit (p > 0.05). The MPOD could replace natural POD to reduce the cost of UA detection due to simple preparation and cheap raw materials, and is expected to achieve the specific detection of some substances, like glucose and cholesterol, combined with glucose oxidase and cholesterol oxidase.


Assuntos
Peroxidase , Ácido Úrico , Peroxidase/química , Cobre , Urato Oxidase/química , Peroxidases
3.
Int J Mol Sci ; 24(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36674855

RESUMO

ANCA-associated vasculitis (AAV) is intricately linked with infections. Toll-like receptors (TLR) provide a potential link between infection and anti-myeloperoxidase (MPO) autoimmunity. TLR9 ligation has been shown to promote anti-MPO autoimmunity and glomerular vasculitis in murine MPO-AAV. This study investigates dendritic cell TLR9 ligation in murine experimental anti-MPO glomerulonephritis. We analyzed autoimmune responses to MPO following transfer of TLR9 stimulated, MPO pulsed dendritic cells and kidney injury following a sub-nephritogenic dose of sheep anti-mouse glomerular basement membrane globulin. TLR9 ligation enhanced dendritic cell activation upregulating CD40 and CD80 expression, promoting systemic anti-MPO autoimmunity and T cell recall responses and exacerbating kidney injury. CD40 upregulation by TLR9 was critical for the induction of nephritogenic autoimmunity. The presence of DEC205, which transports the TLR9 ligand to TLR9 located in the endosome, also promoted kidney injury. This confirms TLR9 mediated dendritic cell activation as a mechanism of anti-MPO autoimmunity in AAV and further defines the link between infection and the generation of MPO specific autoimmune inflammation.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Receptor Toll-Like 9 , Animais , Camundongos , Autoimunidade , Células Dendríticas , Glomerulonefrite/metabolismo , Peroxidase/metabolismo , Ovinos , Receptor Toll-Like 9/metabolismo
4.
Enzyme Microb Technol ; 164: 110192, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36608409

RESUMO

Papain, as a classical cysteine protease, has been widely used in the food, pharmaceutical, chemical, and cosmetic fields. However, there are few information about the peroxidase-like activity of papain catalyzed substrate to produce fluorescence. In this study, we found that papain can catalyze H2O2 to convert o-phenylenediamine (OPD), and generate fluorescence emission at 550 nm under 430 nm excitation. Based on this foundation, we report a papain/OPD/H2O2 system for fluorescence detection of uric acid. The method exhibits a wide linear range of 10-1000 µM with a limit-of-detection of 4.6 µM, and has been successfully used to detect uric acid in human serum. This study paves the way for the application of papain as catalyst for fluorescence detection of different target biomolecules, such as cholesterol, glucose, lactate, for which H2O2 is a product of oxidoreductase enzymes.


Assuntos
Peroxidase , Ácido Úrico , Humanos , Papaína , Peróxido de Hidrogênio/química , Peroxidases , Corantes , Catálise , Limite de Detecção
5.
Methods Mol Biol ; 2617: 227-237, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36656528

RESUMO

In the following chapter a purification process for recombinant Horseradish peroxidase (HRP) produced in Escherichia coli is described. This enzyme is a secretory plant oxidoreductase belonging to the large peroxidase family III within the peroxidase-catalase superfamily of enzymes. It has high biotechnological significance, however, the isolation of the enzyme from its natural source, the horseradish root, has several shortcomings, which makes the development of a recombinant production strategy interesting. The presented protocol covers all process steps from isolation to the final chromatography step; the enzyme is solubilized from insoluble inclusion bodies, refolded and concentrated to yield a high purity enzyme preparation which is comparable to the commercially available plant-derived HRP. Moreover, we believe that this procedure can also be used to process other peroxidases of family II and III of the plant peroxidase superfamily, as they all share the same relevant features like disulfide bonds and a heme group.


Assuntos
Escherichia coli , Peroxidase , Peroxidase do Rábano Silvestre/química , Escherichia coli/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Peroxidases/química , Heme , Corpos de Inclusão
6.
Malar J ; 22(1): 20, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658587

RESUMO

BACKGROUND: Malaria is a growing problem in Africa, with prevalence varies from areas to areas due to several factors including the altitude. This study aimed to investigate the malaria distribution and its relationship with level of some blood parameters and plasma myeloperoxidase (MPO) in population of three localities with different altitudes. METHODS: A total of 150 participants were recruited in each locality and facial body temperature of each was measured using a forehead digital thermometer. Blood samples were collected and used diagnose malaria parasite using the rapid test followed by Giemsa stain microscopy and have the full blood count and MPO level using a colorimetric method. RESULTS: The overall prevalence of falciparum malaria was 34.7%, with no difference between the three communities, but Bambili of high altitude had the highest prevalence (70.7%). A majority of the infected persons had mild malaria, with most cases being asymptomatic (temperature < 37.5 ºC). Patients had significant increase of geometric mean malaria parasite density (GMPD) in Bambili (1755 ± 216 parasites/µL) and Bamenda (1060 ± 2515 parasites/µL of blood) than patients in Santa (737 ± 799 parasites/µL). There was a significant risk to have malaria infection in Bambili (OR = 33.367, p = 0.021) than in Santa (OR = 2.309, p = 0.362). Bambili' participants of 6-10 years showed a high prevalence of malaria (85.7%). GMPD was significantly different between males (p = 0.010) as well as females (p = 0.000). Participants from Santa (11.2 ± 3.2 g/dL) and Bambili (12.6 ± 2.4 g/dL) had a high haemoglobin concentration than those from Bamenda (10.6 ± 2.1 g/dL). There was a significant difference in the WBC counts and platelet counts among infected participants in the study areas. MPO level had an increasing trend among infected participants in Santa (2.378 ± 0.250), Bambili (2.582 ± 0.482) and Bamenda (2.635 ± 0.466). CONCLUSION: The results of the present study demonstrated that altitudinal variations significant impact the risk of population to have malaria with high parasitaemia and may contribute to the malaria prevalence and severity by affecting the haemoglobin concentration, WBC and platelet level and plasma MPO in population.


Assuntos
Malária Falciparum , Malária , Masculino , Feminino , Humanos , Altitude , Camarões/epidemiologia , Prevalência , Peroxidase , Malária/epidemiologia , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Hemoglobinas , Plasmodium falciparum
7.
Int J Mol Sci ; 24(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36674546

RESUMO

We investigated the antioxidant potential of equine mesenchymal stem cells derived from muscle microbiopsies (mdMSCs), loaded by a water-soluble curcumin lysinate incorporated into hydroxypropyl-ß-cyclodextrin (NDS27). The cell loading was rapid and dependent on NDS27 dosage (14, 7, 3.5 and 1 µM). The immunomodulatory capacity of loaded mdMSCs was evaluated by ROS production, on active and total myeloperoxidase (MPO) degranulation and neutrophil extracellular trap (NET) formation after neutrophil stimulation. The intracellular protection of loaded cells was tested by an oxidative stress induced by cumene hydroperoxide. Results showed that 10 min of mdMSC loading with NDS27 did not affect their viability while reducing their metabolism. NDS27 loaded cells in presence of 14, 7 µM NDS27 inhibited more intensively the ROS production, the activity of the MPO released and bound to the NET after neutrophil stimulation. Furthermore, loaded cells powerfully inhibited intracellular ROS production induced by cumene as compared to control cells or cyclodextrin-loaded cells. Our results showed that the loading of mdMSCs with NDS27 significantly improved their antioxidant potential against the oxidative burst of neutrophil and protected them against intracellular ROS production. The improved antioxidant protective capacity of loaded mdMSCs could be applied to target inflammatory foci involving neutrophils.


Assuntos
Curcumina , Animais , Cavalos , Curcumina/farmacologia , Curcumina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Ativação de Neutrófilo , Neutrófilos/metabolismo , Estresse Oxidativo , Músculos/metabolismo , Peroxidase/metabolismo
8.
Int J Mol Sci ; 24(2)2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36674761

RESUMO

The risk of idiosyncratic drug-induced agranulocytosis (IDIAG) markedly constrains the use of clozapine, a neuroleptic with unparalleled efficacy. Most clozapine patients experience an early inflammatory response, likely a necessary step in IDIAG onset. However, most patients do not progress to IDIAG, presumably because of the requirement of specific human leukocyte antigen (HLA) haplotypes, T cell receptors, and other unknown factors. We established that clozapine activates inflammasomes and that myeloperoxidase bioactivation of clozapine generates neoantigens, but the connection between these early mechanistic events remained unknown and, thus, was the aim of this work. We found that the myeloperoxidase inhibitor PF-1355 attenuated myeloperoxidase activity in phorbol myristate acetate (PMA)-differentiated THP-1 macrophages, and it also attenuated clozapine-induced release of inflammatory mediators (e.g., IL-1ß, CXCL1, and C-reactive protein). In vivo, pretreatment of Sprague Dawley rats with PF-1355 significantly attenuated clozapine-induced increases in neutrophil mobilization from the bone marrow to the blood and spleen, as determined using differential blood counts and flow cytometry. Moreover, the clozapine-triggered release of inflammatory mediators (e.g., IL-1ß, calprotectin, CXCL1, and α-1-acid glycoprotein) from the liver, spleen, and bone marrow was dampened by myeloperoxidase inhibition. These data support the working hypothesis that oxidation of clozapine to a reactive metabolite by myeloperoxidase is critical for induction of the inflammatory response to clozapine. Ultimately, a better mechanistic understanding of the early events involved in the immune response to clozapine may elucidate ways to prevent IDIAG, enabling safer, more frequent therapeutic use of this and potentially other highly efficacious drugs.


Assuntos
Antipsicóticos , Clozapina , Neutropenia , Humanos , Ratos , Animais , Clozapina/efeitos adversos , Peroxidase/metabolismo , Ratos Sprague-Dawley , Antipsicóticos/efeitos adversos , Inflamação/tratamento farmacológico , Corantes , Mediadores da Inflamação
9.
Int J Mol Sci ; 24(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36614232

RESUMO

Drought is one of the main environmental factors limiting plant growth and development. The AP2/ERF transcription factor (TF) ERF194 play key roles in poplar growth and drought-stress tolerance. However, the physiological mechanism remains to be explored. In this study, the ERF194-overexpression (OX), suppressed-expression (RNA interference, RNAi), and non-transgenic (WT) poplar clone 717 were used to study the physiology role of ERF194 transcription factor in poplar growth and drought tolerance. Morphological and physiological methods were used to systematically analyze the growth status, antioxidant enzyme activity, malondialdehyde (MDA), soluble sugars, starch, and non-structural carbohydrate (NSC) contents of poplar. Results showed that, compared with WT, OX plants had decrease in plant height, internode length, and leaf area and increased number of fine roots under drought stress. In addition, OX had higher water potential, activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD), contents of chlorophyll, soluble sugar, starch, and NSC, implying that ERF194 positively regulates drought tolerance in poplar. The growth status of RNAi was similar to those of WT, but the relative water content and CAT activity of RNAi were lower than those of WT under drought treatment. Based on the transcriptome data, functional annotation and expression pattern analysis of differentially expressed genes were performed and further confirmed by RT-qPCR analysis. Gene ontology (GO) enrichment and gene expression pattern analysis indicated that overexpression of ERF194 upregulated the expression of oxidoreductases and metabolism-related genes such as POD and SOD. Detection of cis-acting elements in the promoters suggested that ERF194 may bind to these genes through MeJA-responsive elements, ABA-responsive elements, or elements involved in defense and stress responses. The above results show that ERF194 improved tolerance to drought stress in poplar by regulating its growth and physiological factors. This study provides a new idea for the role of ERF194 transcription factor in plant growth and drought-stress response.


Assuntos
Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Antioxidantes/metabolismo , Secas , Peroxidases/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Peroxidase/metabolismo , Água/metabolismo , Amido/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas
10.
Ecotoxicol Environ Saf ; 249: 114409, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508805

RESUMO

Some antimony (Sb) contaminated areas are used for rice cultivation in response to economic demands. However, little is known about the effects of Sb stress on the growth and metabolism of rice roots. Thus, a hydroponic experiment was carried out on the growth, root anatomy, enzyme activity, and metabolism of Nipponbare rice (Oryza sativa L. ssp. japonica cv. Nipponbare) under varying levels of Sb (III) stress (0 mg L-1, 10 mg L-1, and 50 mg L-1). With the increase of Sb concentration, rice root length and root fresh weight declined by 67.8 % and 90.5 % for 10 mg L-1 Sb stress and 94.1 % and 98.4 % for 50 mg L-1 Sb stress, respectively. Anatomical analysis of cross-sections of Sb-treated roots showed an increase in cell wall thickness and an increase in the number of cell mitochondria. The 10 mg L-1 and 50 mg L-1 Sb stress increased the activity of enzyme superoxide dismutase (SOD) in root cells by 1.94 and 2.40 times, respectively. Compared to the control, 10 mg L-1 Sb treatment increased the activity of catalase (CAT) and peroxidase (POD), as well as the concentrations of antioxidant glutathione (GSH) in the root by 1.46, 1.38, and 0.52 times, respectively. However, 50 mg L-1 Sb treatment significantly decreased the activity or content of CAT, POD and GSH by 28.1 %, 13.5 % and 28.2 %, respectively. Nontargeted LC/MS-based metabolomics analysis identified 23 and 13 significantly differential metabolites in rice roots exposed to 10 mg L-1 and 50 mg L-1 Sb, respectively, compared to the control. These differential metabolites were involved in four main metabolic pathways including the tricarboxylic acid cycle (TCA cycle), butanoate metabolism, alanine, aspartate and glutamate metabolism, and alpha-linolenic acid metabolism. Taken together, these findings indicate that Sb stress destroys the structure of rice roots, changes the activity of enzymes, and affects the metabolic pathway, thereby reducing the growth of rice roots and leading to toxicity.


Assuntos
Oryza , Oryza/metabolismo , Antimônio/toxicidade , Antimônio/metabolismo , Antioxidantes/metabolismo , Glutationa/metabolismo , Peroxidase/metabolismo , Raízes de Plantas/metabolismo , Plântula
11.
Biosens Bioelectron ; 223: 115022, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563527

RESUMO

Carbon monoxide (CO) is not only a highly poisonous gas that brings great health risk, but also a significant signaling molecule in body. However, it is still challengeable for development of alternative colorimetric probes to traditional organic chromophores for simple, sensitive and convenient CO sensing. Here, for the first time, we rationally design a novel hydrophilic AgPt-Fe3O4 nanozyme with a unique heterodimeric nanostructure for colorimetric sensing of CO based on the excellent peroxidase-like catalytic activity as well as highly poisonous effect of CO on the nanozyme's catalytic activity. Both experimental evidence and theoretical calculations reveal the trimetallic AgPt-Fe3O4 nanozyme is susceptible to poisoning with the strongest affinity towards CO compared to individual Fe3O4 or Ag-Fe3O4, which is attributed to the adequate exposure of the active metallic sites and efficient interfacial synergy of unique heterodimeric nanostructure. Accordingly, a novel nanozyme-based colorimetric strategy is developed for CO detection with a low detection limit of 5.6 ppb in solution. Furthermore, the probe can be prepared as very convenient test strips and integrated with the portable smartphone platforms for detecting CO gas samples with a low detection limit of 8.9 ppm. Overall, our work proposes guidelines for the rational design of metallic heterogeneous nanostructure to expand the analytical application of nanozyme.


Assuntos
Técnicas Biossensoriais , Nanoestruturas , Colorimetria , Peroxidase/química , Peroxidases , Nanoestruturas/química
12.
Chemosphere ; 313: 137546, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36529171

RESUMO

Lignin-modifying enzymes (LMEs) are impactful biocatalysts in environmental remediation applications. However, LMEs-assisted experimental degradation neglects the molecular basis of pollutant degradation. Furthermore, throughout the remediation process, the inherent hazards of environmental pollutants remain untapped for in-depth toxicological endpoints. In this investigation, a predictive toxicological framework and a computational framework adopting LMEs were employed to assess the hazards of Priority Pollutants (PP) and its possible LMEs-assisted catalytic screening. The potential hazardous outcomes of PP were assessed using Quantitative structure-activity relationship (QSARs)-based techniques including Toxtree, ECOSAR, and T.E.S.T. tools. Toxicological findings revealed positive outcomes in a multitude of endpoints for all PP. The PP compound 2,3,7,8-TCDD (dioxin) was found to exhibit the lowest concentration of aquatic toxicity implementing aquatic model systems; LC50 as 0.01, 0.01, 0.04 (mg L-1) for Fish (96 H), Daphnid (48 H), Green algae (96 H) respectively. T.E.S.T. results revealed that chloroform, and 2-chlorophenol both seem to be developmental toxicants. Subsequently, LMEs-assisted docking procedure was employed in predictive mitigation of PP. The docking approach as predicted degradation revealed the far lowest docking energy score for Versatile peroxidase (VP)- 2,3,7,8-TCDD docked complex with a binding energy of -9.2 (kcal mol-1), involved PHE-46, PRO-139, PRO-141, ILE-148, LEU-165, HIS-169, LEU-228, MET-262, and MET-265 as key interacting amino acid residues. Second most ranked but lesser than VP, Lignin peroxidase (LiP)- 2,3,7,8-TCDD docked complex exhibited a rather lower binding affinity score (-8.8 kcal mol-1). Predictive degradation screening employing comparative docking revealed varying binding affinities, portraying that each LMEs member has independent feasibility to bind PP as substrate. Predictive findings endorsed the hazardous nature of associated PP in a multitude of endpoints, which could be attenuated by undertaking LMEs as a predictive approach to protect the environment and implement it in regulatory considerations.


Assuntos
Poluentes Ambientais , Recuperação e Remediação Ambiental , Dibenzodioxinas Policloradas , Animais , Lignina/química , Oxirredutases , Peroxidase/metabolismo
13.
Anal Methods ; 15(2): 221-227, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36541424

RESUMO

A recyclable peroxidase mimic Fe3O4@polydopamine/Prussian blue (Fe3O4@PDA/PB) composite was facilely prepared by coating PDA on an Fe3O4 nanoparticle core and in situ growth of PB nanoparticles on a PDA shell. The prepared Fe3O4@PDA/PB composite exhibited excellent peroxidase-like activity and can catalytically oxidize the colorless colorimetric substrate 3,3',5,5'-tetramethylbenzidine (TMB) into a blue colored product in the presence of H2O2 at 30 °C in 1 min. The catalytic mechanism was deduced to be the nanozyme-promoted generation of a hydroxyl radical (·OH), and the catalytic behavior followed the typical Michaelis-Menten kinetics. Based on Cr(VI)-boosted peroxidase-like activity of Fe3O4@PDA/PB, a simple and fast colorimetric method for detection of Cr(VI) was developed. Under the optimum conditions, the colorimetric method exhibited wider linear range (100 nM to 140 µM), low LOD (51.1 nM), good selectivity and short detection time (1 min). Moreover, the feasibility of the proposed colorimetric method was evaluated by determination of Cr(VI) in spiked tap water and lake water samples. Good recoveries (95.2-102.9%) and low relative standard deviations (RSDs) (1.6-4.4%) were obtained, showing great promise for practical use.


Assuntos
Colorimetria , Peroxidase , Colorimetria/métodos , Peróxido de Hidrogênio , Peroxidases
14.
Emerg Microbes Infect ; 12(1): 2157338, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36482706

RESUMO

Cytokine dynamics in patients with coronavirus disease 2019 (COVID-19) have been studied in blood but seldomly in respiratory specimens. We studied different cell markers and cytokines in fresh nasopharyngeal swab specimens for the diagnosis and for stratifying the severity of COVID-19. This was a retrospective case-control study comparing Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine ligand 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in 490 (327 patients and 163 control) nasopharyngeal specimens from 317 (154 COVID-19 and 163 control) hospitalized patients. Of the 154 COVID-19 cases, 46 died. Both total and normalized MPO, ADA, CCL22, TNFα, and IL-6 mRNA expression levels were significantly higher in the nasopharyngeal specimens of infected patients when compared with controls, with ADA showing better performance (OR 5.703, 95% CI 3.424-9.500, p < 0.001). Receiver operating characteristics (ROC) curve showed that the cut-off value of normalized ADA mRNA level at 2.37 × 10-3 had a sensitivity of 81.8% and specificity of 83.4%. While patients with severe COVID-19 had more respiratory symptoms, and elevated lactate dehydrogenase, multivariate analysis showed that severe COVID-19 patients had lower CCL22 mRNA (OR 0.211, 95% CI 0.060-0.746, p = 0.016) in nasopharyngeal specimens, while lymphocyte count, C-reactive protein, and viral load in nasopharyngeal specimens did not correlate with disease severity. In summary, ADA appears to be a better biomarker to differentiate between infected and uninfected patients, while CCL22 has the potential in stratifying the severity of COVID-19.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , Interleucina-6/genética , Fator de Necrose Tumoral alfa/genética , Estudos Retrospectivos , Adenosina Desaminase/genética , Adenosina Desaminase/análise , Adenosina Desaminase/metabolismo , Estudos de Casos e Controles , Peroxidase , Ligantes , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Citocinas , Quimiocinas , Nasofaringe , Quimiocina CCL22
15.
Free Radic Biol Med ; 195: 23-35, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36565892

RESUMO

Conversion of the redox probe hydroethidine (HE) to 2-chloroethidium (2-Cl-E+) by myeloperoxidase (MPO)-derived hypochlorous acid (HOCl) provides comparable specificity and superior sensitivity to measurement of 3-chlorotyrosine (3-Cl-Tyr), the gold standard biomarker for MPO chlorinating activity in biological systems. However, a limitation of the former method is the complex mixture of products formed by the reaction of HE with reagent HOCl, coupled with the difficult purification of 2-Cl-E+ from this mixture for analytical purposes. This limitation prompted us to test whether 2-Cl-E+ could be formed by reaction of HE with the strong and widely used chlorinating agent, N-chlorosuccinimide (NCS). Unexpectedly, such reaction yielded 2-chlorohydroethidine (2-Cl-HE) as the major product in addition to 2-Cl-E+, as assessed by high performance liquid chromatography (HPLC), mass spectrometry (MS), and nuclear magnetic resonance (NMR). 2-Cl-HE was also observed to be the major chlorination product formed from HE with both reagent and enzymatically generated HOCl, just as it was formed ex vivo in different healthy and diseased mouse and human tissues upon incubation with glucose/glucose oxidase to generate a flux of hydrogen peroxide (H2O2). Quantification of 2-Cl-HE plus 2-Cl-E+ improved the sensitivity of the HE-based method compared with measurement of only 2-Cl-E+. Moreover, 2-chlorodimidium (2-Cl-D+) was developed as a practical internal standard instead of the previously used internal standard, deuterated 2-Cl-E+ (d5-2-Cl-E+). Overall, the present study describes an improved method for the detection of MPO/chlorinating activity in biological systems of health and disease.


Assuntos
Peróxido de Hidrogênio , Peroxidase , Animais , Humanos , Camundongos , Peróxido de Hidrogênio/química , Peroxidase/metabolismo , Oxirredução , Ácido Hipocloroso/química
16.
Circ Heart Fail ; 16(1): e009446, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36475777

RESUMO

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) are distinct clinical entities, yet there is scant evidence for associations of proteomic signatures with future development of HFpEF versus HFrEF. METHODS: We evaluated the association of 71 protein biomarkers with incident HFpEF versus HFrEF (left ventricular ejection fraction ≥ versus <50%) among Framingham Heart Study participants using multivariable Cox models. RESULTS: Among 7038 participants (mean age 49 years; 54% women), 5 biomarkers were associated with increased risk of incident HFpEF (false discovery rate q<0.05): NT-proBNP (N-terminal pro-B-type natriuretic peptide; hazard ratio [HR], 2.13; 95% CI, 1.52-2.99; P<0.001), growth differentiation factor-15 (HR, 1.67; 95% CI, 1.32-2.12; P<0.001), adrenomedullin (HR, 1.58; 95% CI, 1.23-2.04; P<0.001), uncarboxylated matrix Gla protein (HR, 1.55; 95% CI 1.23-1.95; P<0.001), and C-reactive protein (HR, 1.46; 95% CI, 1.17-1.83; P=0.001). Fourteen biomarkers were associated with incident HFrEF (multivariable P<0.001, q<0.05 for all). Of these, 3 biomarkers were associated with both HF subtypes (NT-proBNP, growth differentiation factor-15, and C-reactive protein). When compared directly, myeloperoxidase, resistin, and paraoxanase-1 were more strongly associated with HFrEF than HFpEF. CONCLUSIONS: We identified 5 protein biomarkers of new-onset HFpEF representing pathways of inflammation, cardiac stress, and vascular stiffness, which partly overlapped with HFrEF. We found 14 biomarkers associated with new-onset HFrEF, with some distinct associations including myeloperoxidase, resistin, and paraoxanase-1. Taken together, these findings provide insights into similarities and differences in the development of HF subtypes. REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT00005121; Unique identifier: NCT0005121.


Assuntos
Insuficiência Cardíaca , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Insuficiência Cardíaca/diagnóstico , Volume Sistólico , Peroxidase , Resistina , Proteína C-Reativa , Proteômica , Função Ventricular Esquerda , Biomarcadores/metabolismo , Fatores de Diferenciação de Crescimento , Prognóstico
17.
Redox Biol ; 59: 102557, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36508858

RESUMO

Neutrophil and airway epithelial cell interactions are critical in the inflammatory response to viral infections including respiratory syncytial virus, Sendai virus, and SARS-CoV-2. Airway epithelial cell dysfunction during viral infections is likely mediated by the interaction of virus and recruited neutrophils at the airway epithelial barrier. Neutrophils are key early responders to viral infection. Neutrophil myeloperoxidase catalyzes the conversion of hydrogen peroxide to hypochlorous acid (HOCl). Previous studies have shown HOCl targets host neutrophil and endothelial cell plasmalogen lipids, resulting in the production of the chlorinated lipid, 2-chlorofatty aldehyde (2-ClFALD). We have previously shown that the oxidation product of 2-ClFALD, 2-chlorofatty acid (2-ClFA) is present in bronchoalveolar lavage fluid of Sendai virus-infected mice, which likely results from the attack of the epithelial plasmalogen by neutrophil-derived HOCl. Herein, we demonstrate small airway epithelial cells contain plasmalogens enriched with oleic acid at the sn-2 position unlike endothelial cells which contain arachidonic acid enrichment at the sn-2 position of plasmalogen. We also show neutrophil-derived HOCl targets epithelial cell plasmalogens to produce 2-ClFALD. Further, proteomics and over-representation analysis using the ω-alkyne analog of the 2-ClFALD molecular species, 2-chlorohexadecanal (2-ClHDyA) showed cell adhesion molecule binding and cell-cell junction enriched categories similar to that observed previously in endothelial cells. However, in contrast to endothelial cells, proteins in distinct metabolic pathways were enriched with 2-ClFALD modification, particularly pyruvate metabolism was enriched in epithelial cells and mitochondrial pyruvate respiration was reduced. Collectively, these studies demonstrate, for the first time, a novel plasmalogen molecular species distribution in airway epithelial cells that are targeted by myeloperoxidase-derived hypochlorous acid resulting in electrophilic 2-ClFALD, which potentially modifies epithelial physiology by modifying proteins.


Assuntos
COVID-19 , Plasmalogênios , Humanos , Animais , Camundongos , Plasmalogênios/química , Plasmalogênios/metabolismo , Peroxidase/metabolismo , Ácido Hipocloroso/metabolismo , Células Endoteliais/metabolismo , COVID-19/metabolismo , SARS-CoV-2/metabolismo , Proteínas/metabolismo , Neutrófilos/metabolismo , Aldeídos/metabolismo
18.
Analyst ; 148(2): 269-277, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36510856

RESUMO

Exploring highly active peroxidase mimics at physiological pH is important for the construction of efficient and convenient colorimetric sensing platforms for detecting small biomolecules. In this work, prepared zinc pyrovanadate (Zn3V2O7(OH)2·2H2O) nanorods exhibit excellent peroxidase-like activity, which is verified by the fast oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) into a blue product (oxTMB) by H2O2 at physiological pH (pH = 7) in 2 min. In addition, the catalytic behaviors of Zn3V2O7(OH)2·2H2O as a peroxidase-like nanozyme conform to the Michaelis-Menten equation. Scavenger experiments prove that the catalytic activity of Zn3V2O7(OH)2·2H2O is ascribed to ˙O2- radicals generated in the process of catalysis. Based on the peroxidase-like activity of the Zn3V2O7(OH)2·2H2O nanozyme, a fast and convenient colorimetric sensor has been constructed to detect H2O2 and epinephrine (EP) under physiological pH. The detection limit of EP is as low as 0.26 µM. In addition, the feasibility of the proposed sensor has been validated to detect H2O2 in milk and EP in serum.


Assuntos
Colorimetria , Nanotubos , Peróxido de Hidrogênio/química , Zinco , Peroxidase/química , Peroxidases/química , Corantes/química , Epinefrina , Concentração de Íons de Hidrogênio
19.
ACS Appl Mater Interfaces ; 15(1): 1486-1494, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36578107

RESUMO

Although two-dimensional (2D) materials with ultrathin geometry and extraordinary electrical attributes have attracted substantial concern, exploiting new-type 2D materials is still a great challenge. In this work, an unprecedented single-layer pure polyoxometalate (POM) 2D material (2D-1) was prepared by ultrasonically exfoliating a one-dimensional (1D)-chain heterometallic crystalline germanotungstate Na4[Ho(H2O)6]2[Fe4(H2O)2(pic)6Ge2W20O72]·16H2O (1) (Hpic = picolinic acid). The 1D polymeric chain of 1 is assembled from particular {Ge2W20}-based [Fe4(H2O)2(pic)6Ge2W20O72]10- segments through bridging [Ho(H2O)6]3+ cations. 2D-1 is formed by π-π interaction driving force among adjacent 1D polymeric chains of 1. Also, the peroxidase-mimicking properties of 2D-1 toward detecting H2O2 were evaluated and good detection result was observed with a limit of detection (LOD) of 58 nM. Density functional theory (DFT) calculation further confirms that 2D-1 displays outstanding catalytic activity and active sites are located on Fe centers and Hpic ligands. Under the catalysis of uricase, uric acid can be transformed to allantoin and H2O2, and then, H2O2 oxidizes TMB to its blue ox-TMB in the presence of 2D-1 as a catalyst. Then, we utilized this cascade reaction to detect uric acid, which also exhibits prominent results. This research opens a door to prepare ultrathin pure POM 2D materials and broadens the scope of potential applications of POMs in biology and iatrology.


Assuntos
Peróxido de Hidrogênio , Peroxidase , Peroxidase/química , Peróxido de Hidrogênio/química , Ácido Úrico , Peroxidases , Polímeros , Corantes , Catálise , Colorimetria/métodos
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