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1.
BMC Genom Data ; 25(1): 41, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711007

ABSTRACT

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.


Subject(s)
Gene Expression Regulation, Plant , Phylogeny , Plant Growth Regulators , Pyrus , Pyrus/genetics , Gene Expression Regulation, Plant/drug effects , Plant Growth Regulators/pharmacology , Plant Growth Regulators/metabolism , Melatonin/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Oxylipins/pharmacology , Cyclopentanes/pharmacology , Peroxidase/genetics , Peroxidase/metabolism , Acetates/pharmacology , Acetates/metabolism , Fruit/genetics , Fruit/growth & development
2.
Anal Chim Acta ; 1309: 342698, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38772661

ABSTRACT

BACKGROUND: The lateral flow immunoassay (LFIA) is widely employed as a point-of-care testing (POCT) technique. However, its limited sensitivity hinders its application in detecting biomarkers with low abundance. Recently, the utilization of nanozymes has been implemented to enhance the sensitivity of LFIA by catalyzing the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The catalytic performance of nanozymes plays a crucial role in influencing the sensitivity of LFIA. RESULTS: The Cornus officinalis Sieb. et Zucc-Pd@Pt (CO-Pd@Pt) nanozyme with good peroxidase-like activity was synthesized herein through a facile one-pot method employing Cornus officinalis Sieb. et Zucc extract as a reducing agent. The morphology and composition of the CO-Pd@Pt nanozyme were characterized using TEM, SEM, XRD, and XPS. As a proof of concept, the as-synthesized CO-Pd@Pt nanozyme was utilized in LFIA (CO-Pd@Pt-LFIA) for the detection of human chorionic gonadotropin (hCG). Compared to conventional gold nanoparticles-based LFIA (AuNPs-LFIA), CO-Pd@Pt-LFIA demonstrated a significant enhancement in the limit of detection (LOD, 0.08 mIU/mL), which is approximately 160 times lower than that of AuNPs-LFIA. Furthermore, experiments evaluating accuracy, precision, selectivity, interference, and stability have confirmed the practical applicability of CO-Pd@Pt-LFIA for hCG content determination. SIGNIFICANCE: The present study presents a novel approach for the synthesis of bimetallic nanozymes through environmentally friendly methods, utilizing plant extracts as both protective and reducing agents. Additionally, an easily implementable technique is proposed to enhance signal detection in lateral flow immunoassays.


Subject(s)
Palladium , Platinum , Palladium/chemistry , Platinum/chemistry , Immunoassay/methods , Humans , Metal Nanoparticles/chemistry , Limit of Detection , Peroxidase/chemistry , Peroxidase/metabolism , Benzidines/chemistry , Catalysis , Oxidation-Reduction
3.
PLoS One ; 19(5): e0301358, 2024.
Article in English | MEDLINE | ID: mdl-38771804

ABSTRACT

Drug-resistant bacteria arising from antibiotic abuse infections have always been a serious threat to human health. Killing bacteria with toxic reactive oxygen species (ROS) is an ideal antibacterial method for treating drug-resistant bacterial infections. Here, we prepared Pt-Ru bimetallic nanoclusters (Pt-Ru NCs) with higher peroxidase (POD)-like activity than Pt monometallic nanoclusters. Pt-Ru can easily catalyze the decomposition of H2O2 to produce ·OH, thereby catalyzing the transformation of 3,3',5,5'-tetramethylbiphenylamine (TMB) to blue oxidized TMB (oxTMB). We utilized the POD-like activity of the Pt-Ru NCs for antibacterial therapy. The results showed that at doses of 40 µg/mL and 16 µg/mL, the Pt-Ru NCs exhibited extraordinary antibacterial activity against E. coli and S. aureus, demonstrating the enormous potential of Pt-Ru NCs as antibacterial agents.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Metal Nanoparticles , Platinum , Ruthenium , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Platinum/chemistry , Platinum/pharmacology , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Ruthenium/chemistry , Ruthenium/pharmacology , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests , Peroxidase/metabolism , Hydrogen Peroxide/chemistry , Catalysis , Humans
4.
Cir Cir ; 92(2): 165-173, 2024.
Article in English | MEDLINE | ID: mdl-38782389

ABSTRACT

OBJECTIVE: The current study aimed to explore the potential protective effect of Passiflora Incarnata L., (PI) in treating IR injury after testicular torsion in rats. MATERIALS AND METHODS: This research investigated the impact of PI on IR damage in male Wistar albino rats. Animals were divided to three groups: group 1 (sham), group 2 (IR), and group 3 (IR+PI). RESULTS: The malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) levels did not significantly differ across the groups (p = 0.830, p = 0.153 and p=0.140, respectively). However, Group 3 demonstrated a superior total antioxidant status (TAS) value compared to Group 2 (p = 0.020). Concurrently, Group 3 presented a significantly diminished mean total oxidant status (TOS) relative to Group 2 (p = 0.009). Furthermore, Group 3 showed a markedly improved Johnsen score relative to Group 2 (p < 0.01). IR caused cell degeneration, apoptosis, and fibrosis in testicular tissues. PI treatment, however, mitigated these effects, preserved seminiferous tubule integrity and promoted regular spermatogenesis. Furthermore, it reduced expression of tumor necrosis factor-alpha (TNF-α), Bax, and Annexin V, signifying diminished inflammation and apoptosis, thereby supporting cell survival (p < 0.01, p < 0.01, p < 0.01, respectively). CONCLUSIONS: This study revealed that PI significantly reduces oxidative stress and testicular damage, potentially benefiting therapies for IR injuries.


OBJETIVO: Explorar el posible efecto protector de Passiflora incarnata L. (PI) en el tratamiento de la lesión por isquemia-reperfusión (IR) después de una torsión testicular en ratas. MÉTODO: Se estudió el impacto de Passiflora incarnata en el daño por IR en ratas Wistar albinas machos. Los animales se dividieron tres grupos: 1 (simulado), 2 (IR) y 3 (IR+PI). RESULTADOS: Los niveles de malondialdehyde (MDA), myeloperoxidase (MPO) y glutathione (GSH) no difirieron significativamente entre los grupos (p = 0.830, p = 0.153 y p = 0.140, respectivamente). Sin embargo, el grupo 3 tuvo un valor de estado antioxidante total (TAS) superior en comparación con el grupo 2 (p = 0.020). Al mismo tiempo, el grupo 3 presentó un estado oxidante total (TOS) medio significativamente disminuido en comparación con el grupo 2 (p = 0.009). El grupo 3 mostró una mejora notable en la puntuación de Johnsen en comparación con el grupo 2 (p < 0.01). La IR causó degeneración celular, apoptosis y fibrosis en los tejidos testiculares. El tratamiento con PI mitigó estos efectos, preservó la integridad de los túbulos seminíferos y promovió la espermatogénesis regular. Además, redujo la expresión de factor de necrosis tumoral alfa, Bax y anexina V, lo que significa una disminución de la inflamación y de la apoptosis, respaldando así la supervivencia celular (p < 0.01, p < 0.01 y p < 0.01, respectivamente). CONCLUSIONES: Este estudio reveló que PI reduce significativamente el estrés oxidativo y el daño testicular, beneficiando potencialmente las terapias para lesiones por IR.


Subject(s)
Disease Models, Animal , Passiflora , Rats, Wistar , Reperfusion Injury , Spermatic Cord Torsion , Animals , Male , Spermatic Cord Torsion/complications , Spermatic Cord Torsion/drug therapy , Reperfusion Injury/prevention & control , Rats , Passiflora/chemistry , Plant Extracts/therapeutic use , Plant Extracts/pharmacology , Antioxidants/pharmacology , Antioxidants/therapeutic use , Apoptosis/drug effects , Phytotherapy , Malondialdehyde/analysis , Malondialdehyde/metabolism , Testis/drug effects , Oxidative Stress/drug effects , Glutathione/metabolism , Peroxidase/metabolism , Peroxidase/analysis , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/metabolism , Spermatogenesis/drug effects
5.
Plant Physiol Biochem ; 211: 108716, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38744087

ABSTRACT

In the context of global climate change, recurrent freeze-thaw cycles (FTC) and concurrent exposure to polystyrene nanoplastics (PSNPs) directly impact crop growth and indirectly affect resilience to abiotic stress. In January 2023, experiments at the Environmental Biology Laboratory, Jilin University, Changchun, China, exposed rye seedlings to 100 nm PSNPs at concentrations of 0, 10, 50, and 100 mg/L for seven days, followed by three FTC. Scanning electron microscopy (SEM) demonstrated that PSNPs migrated from the roots to the leaves, with FTC significantly exacerbating their accumulation within plant tissues. Transmission electron microscopy (TEM) observations showed that FTC disrupted normal cell division, and combined stress from NPs damaged plant organs, particularly chloroplasts, thereby substantially inhibiting photosynthesis. FTC delayed plant phenological stages. Under combined stress, malondialdehyde (MDA) accumulation in plant tissues increased by 15.6%, while hydrogen peroxide (H2O2) content decreased. Simultaneously, the activities of peroxidase (POD) and catalase (CAT) increased by 34.2% and 38.6%, respectively. Molecular docking unveiled that PSNPs could bind to the active center of POD/CAT through hydrogen bonding or hydrophobic interactions. The Integrated Biomarker Response (IBR) index highlighted FTC as a crucial determinant for pronounced effects. Moreover, an apparent dose-dependent effect was observed, with antioxidant enzyme activities in rye seedlings induced by low pollutant concentrations and inhibited by high concentrations. These results indicate that FTC and PSNPs can disrupt plant membrane systems and cause severe oxidative damage. Overall, this study provides compelling scientific evidence of the risks associated with NPs exposure in plants subjected to abiotic stress.


Subject(s)
Freezing , Polystyrenes , Secale , Seedlings , Seedlings/drug effects , Seedlings/metabolism , Polystyrenes/toxicity , Secale/drug effects , Secale/metabolism , Peroxidase/metabolism , Catalase/metabolism , Nanoparticles/toxicity , Molecular Docking Simulation , Malondialdehyde/metabolism
6.
Bull Exp Biol Med ; 176(5): 607-611, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38730105

ABSTRACT

The study presents the killer functions of circulating neutrophils: myeloperoxidase activity, the ability to generate ROS, phagocytic activity, receptor status, NETosis, as well as the level of cytokines IL-2, IL-4, IL-6, IL-17A, and IL-18, granulocyte CSF, monocyte chemotactic protein 1, and neutrophil elastase in the serum of patients with uterine myoma and endometrial cancer (FIGO stages I-III). The phagocytic ability of neutrophils in uterine myoma was influenced by serum levels of granulocyte CSF and IL-2 in 54% of the total variance. The degranulation ability of neutrophils in endometrial cancer was determined by circulating IL-18 in 50% of the total variance. In uterine myoma, 66% of the total variance in neutrophil myeloperoxidase activity was explained by a model dependent on blood levels of IL-17A, IL-6, and IL-4. The risk of endometrial cancer increases when elevated levels of monocyte chemotactic protein 1 in circulating neutrophils are associated with reduced ability to capture particles via extracellular traps (96% probability).


Subject(s)
Chemokine CCL2 , Endometrial Neoplasms , Interleukin-17 , Interleukin-6 , Neutrophils , Humans , Female , Neutrophils/metabolism , Neutrophils/immunology , Endometrial Neoplasms/immunology , Endometrial Neoplasms/blood , Endometrial Neoplasms/pathology , Endometrial Neoplasms/metabolism , Interleukin-6/blood , Chemokine CCL2/blood , Interleukin-17/blood , Middle Aged , Interleukin-4/blood , Peroxidase/blood , Peroxidase/metabolism , Interleukin-18/blood , Uterine Neoplasms/blood , Uterine Neoplasms/immunology , Uterine Neoplasms/pathology , Granulocyte Colony-Stimulating Factor/blood , Granulocyte Colony-Stimulating Factor/metabolism , Phagocytosis , Leiomyoma/blood , Leiomyoma/immunology , Leiomyoma/pathology , Leiomyoma/metabolism , Cytokines/blood , Cytokines/metabolism , Leukocyte Elastase/blood , Leukocyte Elastase/metabolism , Adult , Extracellular Traps/metabolism , Extracellular Traps/immunology , Reactive Oxygen Species/metabolism , Aged , Interleukin-2
7.
ACS Nano ; 18(19): 12367-12376, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38695521

ABSTRACT

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.


Subject(s)
Machine Learning , Metal Nanoparticles , Metal Nanoparticles/chemistry , Catalysis , Peroxidase/chemistry , Peroxidase/metabolism , High-Throughput Screening Assays/methods
8.
Front Immunol ; 15: 1360700, 2024.
Article in English | MEDLINE | ID: mdl-38736886

ABSTRACT

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.


Subject(s)
Monocytes , Myocardial Infarction , Peroxidase , Animals , Myocardial Infarction/immunology , Myocardial Infarction/pathology , Myocardial Infarction/metabolism , Peroxidase/metabolism , Monocytes/immunology , Monocytes/metabolism , Humans , Mice , Male , Cell Movement , Disease Models, Animal , Mice, Inbred C57BL , Female , Neutrophils/immunology , Neutrophils/metabolism , Mice, Knockout , Receptors, CCR2/metabolism , Middle Aged
9.
Biosens Bioelectron ; 258: 116351, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38705074

ABSTRACT

Multifunctional single-atom catalysts (SACs) have been extensively investigated as outstanding signal amplifiers in bioanalysis field. Herein, a type of Fe single-atom catalysts with Fe-nitrogen coordination sites in nitrogen-doped carbon (Fe-N/C SACs) was synthesized and demonstrated to possess both catalase and peroxidase-like activity. Utilizing Fe-N/C SACs as dual signal amplifier, an efficient bipolar electrode (BPE)-based electrochemiluminescence (ECL) immunoassay was presented for determination of prostate-specific antigen (PSA). The cathode pole of the BPE-ECL platform modified with Fe-N/C SACs is served as the sensing side and luminol at the anode as signal output side. Fe-N/C SACs could catalyze decomposition of H2O2 via their high catalase-like activity and then increase the Faraday current, which can boost the ECL of luminol due to the electroneutrality in a closed BPE system. Meanwhile, in the presence of the target, glucose oxidase (GOx)-Au NPs-Ab2 was introduced through specific immunoreaction, which catalyzes the formation of H2O2. Subsequently, Fe-N/C SACs with peroxidase-like activity catalyze the reaction of H2O2 and 4-chloro-1-naphthol (4-CN) to generate insoluble precipitates, which hinders electron transfer and then inhibits the ECL at the anode. Thus, dual signal amplification of Fe-N/C SACs was achieved by increasing the initial ECL and inhibiting the ECL in the presence of target. The assay exhibits sensitive detection of PSA linearly from 1.0 pg/mL to 100 ng/mL with a detection limit of 0.62 pg/mL. The work demonstrated a new ECL enhancement strategy of SACs via BPE system and expands the application of SACs in bioanalysis field.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Electrodes , Hydrogen Peroxide , Iron , Limit of Detection , Luminescent Measurements , Luminol , Prostate-Specific Antigen , Catalysis , Luminescent Measurements/methods , Electrochemical Techniques/methods , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Humans , Luminol/chemistry , Prostate-Specific Antigen/analysis , Prostate-Specific Antigen/blood , Iron/chemistry , Glucose Oxidase/chemistry , Immunoassay/methods , Gold/chemistry , Peroxidase/chemistry , Metal Nanoparticles/chemistry , Nitrogen/chemistry , Carbon/chemistry , Naphthols
10.
Biosens Bioelectron ; 258: 116370, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38744115

ABSTRACT

Protein phosphorylation is a significant post-translational modification that plays a decisive role in the occurrence and development of diseases. However, the rapid and accurate identification of phosphoproteins remains challenging. Herein, a high-throughput sensor array has been constructed based on a magnetic bimetallic nanozyme (Fe3O4@ZNP@UiO-66) for the identification and discrimination of phosphoproteins. Attributing to the formation of Fe-Zr bimetallic dual active centers, the as-prepared Fe3O4@ZNP@UiO-66 exhibits enhanced peroxidase-mimicking catalytic activity, which promotes the electron transfer from Zr center to Fe(II)/Fe(III). The catalytic activity of Fe3O4@ZNP@UiO-66 can be selectively inhibited by phosphoproteins due to the strong interaction between phosphate groups and Zr centers, as well as the ultra-robust antifouling capability of zwitterionic dopamine nanoparticle (ZNP). Considering the diverse binding affinities between various proteins with the nanozyme, the catalytic activity of Fe3O4@ZNP@UiO-66 can be changed to various degree, leading to the different absorption responses at 420 nm in the hydrogen peroxide (H2O2) - 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) system. By simply extracting different absorbance intensities at various time points, a sensor array based on reaction kinetics for the discrimination of phosphoproteins from other proteins is constructed through linear discriminant analysis (LDA). Besides, the quantitative determination of phosphoproteins and identification of protein mixtures have been realized. Further, based on the differential level of phosphoproteins in cells, the differentiation of cancer cells from normal cells can also be implemented by utilizing the proposed sensor array, showing great potential in disease diagnosis.


Subject(s)
Biosensing Techniques , Hydrogen Peroxide , Neoplasms , Phosphoproteins , Zirconium , Biosensing Techniques/methods , Humans , Phosphoproteins/chemistry , Phosphoproteins/metabolism , Hydrogen Peroxide/chemistry , Zirconium/chemistry , Peroxidase/chemistry , Dopamine/chemistry , Limit of Detection , Biomimetic Materials/chemistry , Catalysis
11.
ACS Appl Mater Interfaces ; 16(20): 26870-26885, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38739846

ABSTRACT

Pathogen detection has become a major research area all over the world for water quality surveillance and microbial risk assessment. Therefore, designing simple and sensitive detection kits plays a key role in envisaging and evaluating the risk of disease outbreaks and providing quality healthcare settings. Herein, we have designed a facile and low-cost colorimetric sensing strategy for the selective and sensitive determination of ß-galactosidase producing pathogens. The hexagonal boron nitride quantum dots (h-BN QDs) were established as a nanozyme that showed prominent peroxidase-like activity, which catalyzes 3,3',5,5'-tetramethylbenzidine (TMB) oxidation by H2O2. The h-BN QDs were embedded on a layer-by-layer assembled agarose biopolymer. The ß-galactosidase enzyme partially degrades ß-1,4 glycosidic bonds of agarose polymer, resulting in accessibility of h-BN QDs on the solid surface. This assay can be conveniently conducted and analyzed by monitoring the blue color formation due to TMB oxidation within 30 min. The nanocomposite was stable for more than 90 days and was showing TMB oxidation after incubating it with Escherichia coli (E. coli). The limit of detection was calculated to be 1.8 × 106 and 1.5 × 106 CFU/mL for E. coli and Klebsiella pneumonia (K. pneumonia), respectively. Furthermore, this novel sensing approach is an attractive platform that was successfully applied to detect E. coli in spiked water samples and other food products with good accuracy, indicating its practical applicability for the detection of pathogens in real samples.


Subject(s)
Benzidines , Boron Compounds , Colorimetry , Escherichia coli , Quantum Dots , beta-Galactosidase , Quantum Dots/chemistry , Colorimetry/methods , beta-Galactosidase/metabolism , beta-Galactosidase/chemistry , Escherichia coli/isolation & purification , Escherichia coli/enzymology , Boron Compounds/chemistry , Benzidines/chemistry , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Peroxidase/chemistry , Peroxidase/metabolism , Limit of Detection , Oxidation-Reduction , Klebsiella pneumoniae/enzymology , Klebsiella pneumoniae/isolation & purification
12.
Arch Biochem Biophys ; 756: 110023, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705227

ABSTRACT

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.


Subject(s)
Peroxidase , Staphylococcus aureus , Staphylococcus aureus/enzymology , Humans , Peroxidase/chemistry , Peroxidase/metabolism , Peroxidase/antagonists & inhibitors , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Protein Domains , Amino Acid Sequence , Mutagenesis, Site-Directed , Models, Molecular , Protein Conformation, alpha-Helical
13.
J Immunol Res ; 2024: 4283928, 2024.
Article in English | MEDLINE | ID: mdl-38699219

ABSTRACT

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.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic , Eosinophilia , Registries , Humans , Male , Middle Aged , Female , Adult , Retrospective Studies , Eosinophilia/diagnosis , Eosinophilia/immunology , Eosinophilia/blood , Antibodies, Antineutrophil Cytoplasmic/blood , Antibodies, Antineutrophil Cytoplasmic/immunology , Granulomatosis with Polyangiitis/diagnosis , Granulomatosis with Polyangiitis/immunology , Aged , Churg-Strauss Syndrome/diagnosis , Churg-Strauss Syndrome/immunology , Churg-Strauss Syndrome/epidemiology , Peroxidase/immunology , Eosinophils/immunology
14.
Cells ; 13(10)2024 May 20.
Article in English | MEDLINE | ID: mdl-38786103

ABSTRACT

Cigarette smoke is one of the main factors in Chronic Obstructive Pulmonary Disease (COPD), a respiratory syndrome marked by persistent respiratory symptoms and increasing airway obstruction. Perturbed NAD+/NADH levels may play a role in various diseases, including lung disorders like COPD. In our study, we investigated the preventive effect of NADH supplementation in an experimental model of COPD induced by cigarette smoke extract (CSE). N = 64 mice randomly distributed in eight groups were injected with NADH (two doses of 100 mg/kg or 200 mg/kg) or dexamethasone (2 mg/kg) before being exposed to CSE for up to 9 weeks. Additionally, NADH supplementation preserved lung antioxidant defenses by preventing the functional loss of key enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase, and the expression levels of glutathione (GSH) (n = 4, p < 0.001). It also reduced oxidative damage markers, such as malondialdehyde (MDA) and nitrites (n = 4, p < 0.001). A marked increase in tissue myeloperoxidase activity was assessed (MPO), confirming neutrophils implication in the inflammatory process. The latter was significantly ameliorated in the NADH-treated groups (p < 0.001). Finally, NADH prevented the CSE-induced secretion of cytokines such as Tumor Necrosis Factor alpha (TNF-α), IL-17, and IFN-y (n = 4, p < 0.001). Our study shows, for the first time, the clinical potential of NADH supplementation in preventing key features of COPD via its unique anti-inflammatory and antioxidant properties.


Subject(s)
Disease Models, Animal , Mice, Inbred BALB C , NAD , Pneumonia , Pulmonary Disease, Chronic Obstructive , Animals , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/prevention & control , Pulmonary Disease, Chronic Obstructive/etiology , NAD/metabolism , Mice , Pneumonia/prevention & control , Pneumonia/metabolism , Pneumonia/pathology , Injections, Intraperitoneal , Smoke/adverse effects , Oxidative Stress/drug effects , Male , Antioxidants/metabolism , Antioxidants/pharmacology , Cytokines/metabolism , Lung/pathology , Lung/metabolism , Lung/drug effects , Peroxidase/metabolism
15.
Int J Biol Macromol ; 269(Pt 2): 132115, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38719015

ABSTRACT

Bacterial infections pose a serious threat to human health and socioeconomics worldwide. In the post-antibiotic era, the development of novel antimicrobial agents remains a challenge. Polyphenols are natural compounds with a variety of biological activities such as intrinsic antimicrobial activity and antioxidant properties. Metal-polyphenol obtained by chelation of polyphenol ligands with metal ions not only possesses efficient antimicrobial activity but also excellent biocompatibility, which has great potential for application in biomedical and food packaging fields. Herein, we developed metal-polyphenol coordination nanosheets named copper oxidized tannic acid quinone (CuTAQ) possessing efficient antibacterial and anti-biofilm effects, which was synthesized by a facile one-pot method. The synthesis was achieved by chelation of partially oxidized tannic acid (TA) with Cu2+ under mild conditions, which supports low-cost and large-scale production. It was demonstrated that CuTAQ exhibited high antibacterial activity via disrupting the integrity of bacterial cell membranes, inducing oxidative stress, and interfering with metabolism. In addition, CuTAQ exhibits excellent peroxidase catalytic activity and photothermal conversion properties, which play a significant role in enhancing its bactericidal and biofilm scavenging abilities. This study provides insights for rational design of innovative metal-polyphenol nanomaterials with efficient antimicrobial properties.


Subject(s)
Anti-Bacterial Agents , Nanostructures , Polyphenols , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polyphenols/chemistry , Polyphenols/pharmacology , Nanostructures/chemistry , Tannins/chemistry , Tannins/pharmacology , Biofilms/drug effects , Copper/chemistry , Copper/pharmacology , Peroxidase/metabolism , Microbial Sensitivity Tests , Humans
16.
BMC Infect Dis ; 24(1): 534, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802752

ABSTRACT

BACKGROUND AND OBJECTIVES: Central nervous system infections, typified by bacterial meningitis, stand as pivotal emergencies recurrently confronted by neurologists. Timely and precise diagnosis constitutes the cornerstone for efficacious intervention. The present study endeavors to scrutinize the influence of inflammatory protein levels associated with neutrophils in cerebrospinal fluid on the prognosis of central nervous system infectious maladies. METHODS: This retrospective case series study was undertaken at the Neurology Department of the Second Hospital of Shandong University, encompassing patients diagnosed with infectious encephalitis as confirmed by PCR testing and other diagnostic modalities spanning from January 2018 to January 2024. The quantification of MPO and pertinent inflammatory proteins within patients' cerebrospinal fluid was accomplished through the utilization of ELISA. RESULTS: We enlisted 25 patients diagnosed with bacterial meningitis, ascertained through PCR testing, and stratified them into two groups: those with favorable prognoses (n = 25) and those with unfavorable prognoses (n = 25). Following assessments for normality and variance, notable disparities in CSF-MPO concentrations emerged between the prognostic categories of bacterial meningitis patients (P < 0.0001). Additionally, scrutiny of demographic data in both favorable and unfavorable prognosis groups unveiled distinctions in CSF-IL-1ß, CSF-IL-6, CSF-IL-8, CSF-IL-18, CSF-TNF-α levels, with correlation analyses revealing robust associations with MPO. ROC curve analyses delineated that when CSF-MPO ≥ 16.57 ng/mL, there exists an 83% likelihood of an adverse prognosis for bacterial meningitis. Similarly, when CSF-IL-1ß, CSF-IL-6, CSF-IL-8, CSF-IL-18, and CSF-TNF-α levels attain 3.83pg/mL, 123.92pg/mL, 4230.62pg/mL, 35.55pg/mL, and 35.19pg/mL, respectively, there exists an 83% probability of an unfavorable prognosis for bacterial meningitis. CONCLUSION: The detection of neutrophil extracellular traps MPO and associated inflammatory protein levels in cerebrospinal fluid samples holds promise in prognosticating bacterial meningitis, thereby assuming paramount significance in the prognostic evaluation of patients afflicted with this condition.


Subject(s)
Meningitis, Bacterial , Neutrophils , Humans , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/diagnosis , Retrospective Studies , Prognosis , Female , Male , Adult , Middle Aged , Case-Control Studies , Peroxidase/cerebrospinal fluid , Aged , Biomarkers/cerebrospinal fluid , Young Adult
17.
Plant Physiol Biochem ; 211: 108672, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38718531

ABSTRACT

Luminescent materials can adjust the spectrum of light energy utilization by plants. However, current research on the effects of luminescent materials on aquatic plants and periphytic biofilms is limited. This study investigated the effects of the luminescent materials 4-(di-p-tolylamino) benzaldehyde-A (DTB-A) and 4-(di-p-tolylamino) benzaldehyde-M (DTB-M) on the submerged macrophyte Vallisneria natans (V. natans) and periphytic biofilm. Result demonstrated that low concentrations of DTB (0.1 µM) significantly promoted the growth and photosynthetic rate of V. natans. In terms of enzyme activity, exposure to a higher concentration of DTB (10 µM) increased the activities of peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT). A combination of DTB-A and DTB-M treatment significantly changed the V. natans morphology and physiological characteristics, reducing the thickness of the cell wall and subsequently, promoting protein accumulation in leaves. There was no difference in the removal of ammonia or phosphate by V. natans at the 0.1 µM concentration, and the removal of ammonia and phosphate by V. natans decreased significantly as the concentration of luminescent material increased. A total of 3563 OTUs were identified in the biofilm community. The microbial community was dominated by Pseudomonas and Fusobacteria. Furthermore, results showed that an obvious decrease in diversity in the DTB-A and DTB-M mixed treatment group. In addition, the migratory aggregation of DTB molecules in plants was observed by fluorescence imaging. Overall, these findings extend our understanding of the mechanism of effect of luminescent materials on submerged macrophytes and their periphytic microorganisms.


Subject(s)
Biofilms , Hydrocharitaceae , Biofilms/drug effects , Biofilms/growth & development , Hydrocharitaceae/metabolism , Hydrocharitaceae/microbiology , Benzaldehydes/metabolism , Benzaldehydes/pharmacology , Photosynthesis/drug effects , Luminescence , Catalase/metabolism , Peroxidase/metabolism , Plant Leaves/metabolism , Superoxide Dismutase/metabolism , Luminescent Agents/metabolism
18.
Mikrochim Acta ; 191(6): 331, 2024 05 15.
Article in English | MEDLINE | ID: mdl-38744722

ABSTRACT

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.


Subject(s)
Colorimetry , Limit of Detection , Metal-Organic Frameworks , Salmonella enterica , Colorimetry/methods , Salmonella enterica/isolation & purification , Salmonella enterica/chemistry , Metal-Organic Frameworks/chemistry , Food Microbiology/methods , Food Contamination/analysis , Peroxidase/chemistry
19.
Mol Immunol ; 170: 26-34, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38603988

ABSTRACT

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.


Subject(s)
Flounder , Immunity, Innate , Neutrophils , Peroxidase , Animals , Flounder/immunology , Peroxidase/metabolism , Neutrophils/immunology , Neutrophils/metabolism , Immunity, Innate/immunology , Gills/immunology , Head Kidney/immunology , Fish Proteins/metabolism , Fish Proteins/immunology , Fish Proteins/genetics , Flow Cytometry , Spleen/immunology
20.
Mikrochim Acta ; 191(5): 268, 2024 04 17.
Article in English | MEDLINE | ID: mdl-38627271

ABSTRACT

Hybrid nanozyme graphene quantum dots (GQDs) deposited TiO2 nanotubes (NTs) on titanium foil (Ti/TiO2 NTs-GQDs) were manufactured by bestowing the hybrid with the advantageous porous morphology, surface valence states, high surface area, and copious active sites. The peroxidase-like activity was investigated through the catalytic oxidation of chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, which can be visualized by the eyes. TiO2 NTs and GQDs comprising oxygen-containing functional groups can oxidize TMB in the presence of H2O2 by mimicking peroxidase enzymes. The peroxidase-mimicking activity of hybrid nanozyme was significantly escalated by introducing light illumination due to the photosensitive features of the hybrid material. The peroxidase-like activity of Ti/TiO2 NTs-GQDs enabled H2O2 determination over the linear range of 7 to 250 µM, with a LOD of 2.1 µM. The satisfying peroxidase activity is possibly due to the unimpeded access of H2O2 to the catalyst's active sites. The porous morphology provides the easy channeling of reactants and products. The periodic structure of the material also gave rise to acceptable reproducibility. Without material functionalization, the Ti/TiO2 NTs-GQDs can be a promising substitute for peroxidases for H2O2 detection.


Subject(s)
Benzidines , Graphite , Nanotubes , Quantum Dots , Graphite/chemistry , Peroxidase/chemistry , Quantum Dots/chemistry , Hydrogen Peroxide/chemistry , Reproducibility of Results , Nanotubes/chemistry
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