Myeloperoxidase Content Research Articles

Myeloperoxidase in the pericardial fluid improves the performance of prediction rules for postoperative atrial fibrillation.

After surgery, inflammation is a prominent factor influencing postoperative atrial fibrillation. Myeloperoxidase is a major contributor to inflammatory responses after surgical tissue damage. We evaluated whether myeloperoxidase is associated with postoperative atrial fibrillation clinically and in an animal model. This prospective cohort study included patients undergoing isolated coronary artery bypass grafting. Myeloperoxidase concentrations in blood and pericardial fluid were determined at baseline and 6, 12, and 18hours after coronary artery bypass grafting. Myeloperoxidase activity in blood, pericardial fluid, and atrium were also evaluated in a canine coronary artery bypass grafting model. Electrophysiologic, histologic, and immunohistochemistry analyses were performed to explore underlying mechanisms. Postoperative atrial fibrillation occurred in 45 of 137 patients (32.8%). Patients with postoperative atrial fibrillation had significantly higher serum and pericardial myeloperoxidase levels. Individual clinical and surgical factors had moderate predictive value (area under the curve, 0.760) for postoperative atrial fibrillation. Discrimination improved remarkably when myeloperoxidase was combined with other parameters (area under the curve, 0.901). Pericardial myeloperoxidase at 6hours postoperatively was the strongest independent predictor of postoperative atrial fibrillation (odds ratio, 19.215). The rate of postoperative atrial fibrillation increased exponentially across pericardial myeloperoxidase grades. Compared with controls, coronary artery bypass grafting-treated dogs showed higher atrial fibrillation vulnerability and maintenance, shorter atrial effective refractory period, attenuated connexin 43 expression, and increased myocardial and pericardial myeloperoxidase activity. Connexin 43 expression and atrial effective refractory period were strongly negatively correlated with myocardial and pericardial myeloperoxidase activity. Myeloperoxidase is linked to postoperative atrial fibrillation, and the ability to predict postoperative atrial fibrillation was remarkably improved by adding pericardial myeloperoxidase. Myeloperoxidase-related atrial structural and electrical remodeling is a physiologic substrate for this arrhythmia.

LC-ESI-MS phenolic contents assessment, antioxidant, and protective ability of Punica granatum root bark extract against ethanol-induced gastric ulcer in rats: in silico H+, K+-ATPase inhibitory pathway study.

The objectives of the current study were to evaluate the Punica granatum root bark extract's (PGE) antioxidant and gastroprotective activities against ethanol-induced gastric ulcers in Wistar rats and to elucidate the putative mechanism of action using in silico analysis. The PGE phytochemical study shows high levels of phenolics, flavonoids, tannins, and polysaccharides. In vitro, the PGE was more effective at scavenging hydroxyl radicals than quercetin and had lower ferric reducing activity than catechin. In vivo, it was revealed that pretreatment of ethanol-ulcerated rats with PGE at oral doses of 100, 200, and 400mg/kg b.w. offered a dose-dependent shield against ethanol-induced ulcers when compared to Omeprazole (20mg/kg b.w.) by preventing the development of deep ulcer lesions, lowering gastric juice output and pH rises, boosting gastric mucus production and antioxidant enzyme levels, and attenuating malondialdehyde and myeloperoxidase contents. Moreover, the liquid chromatography-mass spectrometry analysis of PGE identified 5 phenolic acids and 4 flavonoids, which revealed an in silico high oral bioavailability, drug-likenesses, and good binding affinities and thus inhibitory effects on the gastric H+, K+-ATPase enzyme. PGE may have synergistic antioxidant, anti-inflammatory, and H+, K+-proton pump inhibitory actions that contribute to its antiulcer efficacy.

Links Between Vitamin D-Binding Protein, Alpha-1 Antitrypsin and Neutrophil Proteins in Meconium.

Alpha-1 antitrypsin (AAT), vitamin-D binding protein (VDBP) and neutrophil granule proteins are specifically related to the neutrophil function and may be considered candidate biomarkers detected and measured in meconium (the first feces of newborn infants) as signals indicating abnormal processes in the fetal stage. Individual proteins found in meconium can be a source of information pertaining to the intrauterine metabolic processes. Concentrations of AAT, VDBP, calprotectin, myeloperoxidase, lactoferrin and elastase were measured using ELISA tests in 80 meconium samples collected from 19 healthy, full-term neonates. The meconium concentrations of VDBP and AAT (mean±SD, [mg/g meconium]: 3.74±6.93, 3.72±1.79, respectively) were approximately 1000 times higher than those of the protein granule proteins calprotectin, myeloperoxidase, elastase and lactoferrin (mean ± SD, [µg/g meconium]: 285.7±215.8, 1.83±1.73, 1.72±2.70, 45.58±78.89, respectively). The correlation between VDBP and AAT was negative (r= - 0.40. p=0.000) and those between VDBP and calprotectin (r=0.38, p=0.000) and VDBP and myeloperoxidase (r=0.45, p=0.000) were positive. AAT was found to correlate positively with lactoferrin (r=0.38, p=0.000). The correlations between the concentrations of VDBP and AAT, and with neutrophil granule proteins observed in meconium indicate their functional relationship in the intrauterine environment of the developing fetus. Meconium can be seen as an apparently underutilized source of biomarkers for evaluation of metabolic processes specific to fetal development.

Adequacy of Iodine Status and Associations with Gut Health: A Prospective Cohort Study among Infants in 8 Low- and Middle-Income Countries

BackgroundEnvironmental enteric dysfunction increases the likelihood of micronutrient deficiencies among infants, but few studies have assessed the potential impact of gut health on urinary iodine concentration (UIC) among this vulnerable group. ObjectivesWe describe the trends of iodine status among infants from 6 to 24 mo old and examine the associations between intestinal permeability, inflammation, and UIC from 6 to 15 mo of age. MethodsData from 1557 children enrolled in this birth cohort study conducted in 8 sites were included in these analyses. UIC was measured at 6, 15, and 24 mo of age by using the Sandell-Kolthoff technique. Gut inflammation and permeability were assessed using the concentrations of fecal neopterin (NEO), myeloperoxidase (MPO) and alpha-1–antitrypsin (AAT), and lactulose–mannitol ratio (LM). A multinomial regression analysis was used to assess the classified UIC (deficiency or excess). Linear mixed regression was used to test the effect of interactions among biomarkers on logUIC. ResultsAll studied populations had adequate (≥100 μg/L) to excess (≥371 μg/L) median UIC at 6 mo. Between 6 and 24 mo, 5 sites displayed a significant decline in the infant’s median UIC. However, median UIC remained within the optimal range. An increase of NEO and MPO concentrations by +1 unit in ln scale reduced the risk of low UIC by 0.87 (95% CI: 0.78–0.97) and 0.86 (95% CI: 0.77–0.95), respectively. AAT moderated the association between NEO and UIC (P < 0.0001). The shape of this association appears to be asymmetric and in a reverse J-shape, with a higher UIC observed at both lower NEO and AAT concentrations. ConclusionsExcess UIC was frequent at 6 mo and tended to normalize at 24 mo. Aspects of gut inflammation and increased permeability appear to reduce the prevalence of low UIC in children aged 6 to 15 mo. Programs addressing iodine-related health should consider the role of gut permeability in vulnerable individuals.

The Protective Role of Scorias spongiosa Polysaccharide-Based Microcapsules on Intestinal Barrier Integrity in DSS-Induced Colitis in Mice.

Scorias spongiosa, a type of edible fungus, is beneficial for intestinal health. However, the mechanisms by which polysaccharides derived from S. spongiosa contribute to the integrity of the intestinal barrier have been little investigated. In the present study, 40 C57BL/6J mice were assigned into five groups: (1) Normal; (2) Dextran sulfate sodium (DSS)Administration; (3) DSS + Uncapped polysaccharides; (4) DSS + Low microcapsules; (5) DSS + High microcapsules. After one week of administration of S. spongiosa polysaccharides, all mice, excluding the Normal group, had free access to the drinking water of 3.5% DSS for seven days. Serum and feces were then taken for analysis. Scanning electron microscopy analysis indicated the structure of the micro-capped polysaccharides with curcumin was completed with a rough surface, which differs from the uncapped polysaccharides. Noticeably, S. spongiosa polysaccharides enhanced intestinal barrier integrity as evidenced by increasing the protein levels of Claudin-1, ZO-1 and ZO-2. Low-capped polysaccharides mitigated the DSS-induced oxidative stress by increasing catalase (CAT) concentration and decreasing malondialdehyde (MDA) and myeloperoxidase (MPO) concentrations. Besides, DSS treatment caused a disturbance of inflammation and the contents of IL-1β, IL-6, TNF-α and CRP were downregulated and the contents of IL-4, IL-10 and IFN-γ were upregulated by S. spongiosa polysaccharides. Research on the potential mechanisms indicated that S. spongiosa polysaccharides inhibited the DSS-triggered activation of NF-κB signaling. Moreover, the JAK/STAT1 and MAPK pathways were suppressed by S. spongiosa polysaccharides in DSS-challenged mice, with Lcap showing the strongest efficacy. 16S rDNA amplicon sequencing revealed that the richness and diversity of the microbial community were reshaped by S. spongiosa polysaccharide ingestion. Therefore, our study substantiated that S. spongiosa polysaccharides exhibited protective effects against colitis mice by reshaping the intestinal microbiome and maintaining the balance of intestinal barrier integrity, antioxidant capacity and colonic inflammation through regulation of the NF-κB-STAT1-MAPK axis.

Total flavonoids of Chrysanthemum indicum L inhibit acute pancreatitis through suppressing apoptosis and inflammation

Acute pancreatitis (AP) is one of the most common acute abdomen. Inflammation and apoptosis are closely linked with AP development. Total flavonoids of Chrysanthemum indicum L (TFC) has been proved to inhibit inflammation and apoptosis. If TFC could suppress AP remains unclear. AP animal and cell models were established with Cerulein. The pancreatic tissue injury was measured with HE staining. Inflammatory factors were detected with ELISA method. The protein expression was evaluated with Western blotting. Inhibition of AP in vivo was achieved by TFC by inhibiting serum amylase, myeloperoxidase (MPO), and water content of pancreatic tissue. The increased inflammatory response and activation of NF-κB signaling pathway in AP rats were inhibited after TFC treatment. The activation of NF-κB signaling pathway, increase of cell apoptosis and inflammatory factors in AR42J cells were suppressed by TFC. We demonstrated that TFC could significantly inhibit AP through restraining serum amylase, MPO, water content of pancreatic tissue, inflammation levels, apoptosis, and NF-κB signaling pathway activation. This study might clarify the potential inhibition mechanism of TFC in AP development.

Medium chain fatty acid supplementation improves animal metabolic and immune status during the transition period: A study on dairy cattle.

The transition period is the stage of the high incidence of metabolic and infectious diseases in dairy cows. Improving transition dairy cows' health is crucial for the industry. This study aimed to determine the effects of dietary supplementation medium-chain fatty acids (MCFAs) on immune function, metabolic status, performance of transition dairy cows. Twenty multiparous Holstein cows randomly assigned to two treatments at 35 d before calving. 1) CON (fed the basal 2) MCFA treatment (basal diet was supplemented at an additional 20 g MCFAs mixture every day) until 70 d after calving. The results showed that the serum amyloid A myeloperoxidase concentrations in the blood of cows in MCFA treatment significantly decreased during the early lactation (from 1 d to 28 d after calving) 0.03, 0.04, respectively) compared with the CON, while the tumor necrosis factor concentration was significantly decreased at 56 d after calving (P = 0.02). In addition, the concentration of insulin in the pre-calving (from 21 d before calving to calving) blood of cows in MCFA treatment was significantly decreased (P = 0.04), and concentration of triglyceride also showed a downward trend at 28 d after calving 0.07). Meanwhile, MCFAs supplementation significantly decreased the concentrations of lithocholic acid, hyodeoxycholic acid, and hyocholic acid in the blood at 1 d calving (P = 0.02, < 0.01, < 0.01, respectively), and the level of hyocholic acid taurocholic acid concentrations (P < 0.01, = 0.01, respectively) decreased dramatically at 14 d after calving. However, compared with the CON, the pre-calving dry matter intake and the early lactation milk yield in MCFA treatment were significantly decreased (P = 0.05, 0.02, respectively). In conclusion, MCFAs supplementation transition diet could improve the immune function and metabolic status of dairy cows, and the health of transition cows might be beneficial from the endocrine status.

Characterization of Myeloperoxidase in the Healthy Equine Endometrium.

Myeloperoxidase (MPO), as a marker of neutrophil activation, has been associated with equine endometritis. However, in absence of inflammation, MPO is constantly detected in the uterine lumen of estrous mares. The aim of this study was to characterize MPO in the uterus of mares under physiological conditions as a first step to better understand the role of this enzyme in equine reproduction. Total and active MPO concentrations were determined, by ELISA and SIEFED assay, respectively, in low-volume lavages from mares in estrus (n = 26), diestrus (n = 18) and anestrus (n = 8) in absence of endometritis. Immunohistochemical analysis was performed on 21 endometrial biopsies randomly selected: estrus (n = 11), diestrus (n = 6) and anestrus (n = 4). MPO, although mostly enzymatically inactive, was present in highly variable concentrations in uterine lavages in all studied phases, with elevated concentrations in estrus and anestrus, while in diestrus, concentrations were much lower. Intracytoplasmic immunoexpression of MPO was detected in the endometrial epithelial cells, neutrophils and glandular secretions. Maximal expression was observed during estrus in mid and basal glands with a predominant intracytoplasmic apical reinforcement. In diestrus, immunopositive glands were sporadic. In anestrus, only the luminal epithelium showed residual MPO immunostaining. These results confirm a constant presence of MPO in the uterine lumen of mares in absence of inflammation, probably as part of the uterine mucosal immune system, and suggest that endometrial cells are a source of uterine MPO under physiological cyclic conditions.

Enhanced neutrophil extracellular traps formation in AF patients with dilated left atrium.

Atrial fibrillation (AF) is associated with cardiac remodelling and prothrombotic state. Enhanced neutrophil extracellular traps (NETs) formation has been reported in AF, contributing to thromboembolism. We investigated whether increased left atrium (LA) diameter and reduced left ventricular ejection fraction (LVEF) affect NETs formation and prothrombotic state in AF patients. In 243 AF patients (median CHA2 DS2 -VASc=4) we measured LA diameter and LVEF, 123 of them with LVEF<50%. Moreover, we determined 3 markers of NETosis: circulating citrullinated histone H3 (H3cit), myeloperoxidase (MPO) and peptidylarginine deiminase 4 (PAD4), along with prothrombotic markers, including endogenous thrombin potential, plasma fibrin clot permeability (Ks ) and clot lysis time (CLT). Ischaemic cerebrovascular events, major bleeding and death were recorded during a median follow-up of 53 months, on anticoagulation. LA diameter correlated positively with H3cit, MPO and PAD4, while LVEF was inversely associated with the same NETosis markers. After adjustment for age and body mass index, concentrations of MPO (per 10units; β=-1.9, 95%CI -3.40;-0.42) and H3cit (per 10units; β=2.02, 95%CI 0.61-3.42) were independently associated with LVEF and LA diameter. LA diameter, but not LVEF, correlated inversely with Ks and positively with CLT. The Cox regression analysis revealed that H3cit >6.16 ng/mL (HR=21.76, 95%CI 2.85-166.28, p=.003) and LA diameter > 46 mm (HR=2.89, 95%CI 1.04-8.03, p=.043) independently predicted cerebrovascular ischaemic events (1.9%/year). This hypothesis-generating study suggests that in AF enlarged LA diameter and reduced LVEF are associated with enhanced NETs formation, which might have clinical importance and contribute to thromboembolic events despite anticoagulation.

Immature neutrophil is associated with coronary plaque vulnerability based on optical coherence tomography analysis

IntroductionHigh neutrophil to lymphocyte ratio is considered to predict poor prognosis of acute coronary syndrome (ACS). However, the association of neutrophil subpopulation with plaque vulnerability and the incidence of ACS remains unknown. Methods and resultsBlood samples from 48 patients with unstable angina (UA), 31 with ST-segment elevation myocardial infarction (STEMI) and 33 healthy controls were collected at admission. The morphology of coronary plaques in 48 UA patients were further evaluated by optical coherence tomography (OCT). According to maturation stages of neutrophils and the expression of CD10 and CD101, circulating neutrophils could be divided into pre-neutrophils (CD101−CD10−), immature neutrophils (CD101+CD10−) and mature neutrophils (CD101+CD10+). While the number of pre-neutrophil was quite low in blood and comparable among three groups, the absolute counts and percentage of CD10− immature neutrophils were higher in peripheral bloods of UA and STEMI patients compared with those in healthy controls. The concentration of plasma myeloperoxidase was positively associated with the percentage of CD10− immature neutrophils. Furthermore, UA patients with thin-cap fibroatheroma (TCFA) observed by OCT had a higher proportion and larger number of immature neutrophils as compared to those without TCFA. The percentage of immature neutrophils also closely correlated with plaque rupture and the feature of vulnerable plaque, including thinner fibrous cap and larger lipid core, but did not associate with percent lumen stenosis. ConclusionOur findings emphasize that the abnormally increased level of CD10− immature neutrophils may sever as a promising marker of the incidence of ACS and plaque vulnerability.

NADPH Oxidase-Mediated Testicular Oxidative Imbalance Regulates the TXNIP/NLRP3 Inflammasome Axis Activation after Ischemia Reperfusion Injury.

Oxidative stress, inflammation and germ cell death are the main characteristics of testicular ischemia reperfusion injury (tIRI), which is considered as the underlying mechanism for testicular torsion and detorsion. The study aimed to examine the effect of tIRI-activated NADPH oxidase (NOX) on the expression of the NLRP3 inflammasome pathway components. Three groups of male Sprague-Dawley rats (n = 12 each) were studied: sham, unilateral tIRI only and tIRI treated with apocynin, a NOX-specific inhibitor. The tIRI rat model was subjected to 1 h of ischemia followed by 4 h of reperfusion. H&E staining, real time PCR, biochemical assays, and Western blot were utilized to evaluate spermatogenic damage, gene expression, oxidative stress markers, and NLRP3 pathway components, respectively. As a result of tIRI, decreased total antioxidant capacity and suppressed activities of superoxide dismutase and catalase were associated with spermatogenic arrest. The components of the NLRP3 inflammasome pathway (TXNIP, NLRP3, ASC, caspase-1, GSDMD, MMP-9) were upregulated transcriptionally and post-transcriptionally during tIRI. In parallel, tissue inflammation was demonstrated by a marked increase in the concentrations of myeloperoxidase, IL-1β, and IL-18. Apocynin treatment prevented testicular oxidative stress and inflammation. Thus, NOX inhibition by apocynin prevented ROS accumulation, proinflammatory cytokine overexpression and NLRP3 inflammasome activation during tIRI.

Blood concentrations of mediators released from activated neutrophils are related to the severity of alcohol-induced liver damage.

Immune dysregulation and neutrophil infiltration are hallmarks of alcohol-related liver disease (ALD). Our objective was to evaluate the blood profile of neutrophil-derived mediators [neutrophil elastase (NE), myeloperoxidase (MPO), alpha1-antitrypsin (A1AT)], and their potential relevance in ALD. 62 patients with ALD /47 males, and 15 females, aged 49,2 ± 9,9/ were prospectively recruited and distributed according to their 1/ gender, 2/ severity of liver dysfunction (by Child-Turcotte-Pugh, MELD scores, and mDF) 3/ presence of complications of ALD complications, and followed for 90 days. 24 age- and sex-matched healthy volunteers served as the control group. Neutrophil-derived biomarkers were quantified using enzyme-linked immunosorbent assays (ELISAs). Blood concentrations of MPO and NE were significantly higher in ALD patients in comparison with controls. A1AT levels were not different. There were no gender-related differences in the studied biomarker levels. Both NE and MPO correlated with routine markers of inflammation, while NE with MELD and mDF scores. Patients with a severe ALD course i.e. MELD>20 or mDF>32, presented with significantly higher NE blood concentrations. Our results point out the critical role of neutrophils in the pathogenesis of ALD. NE and MPO correlated with the intensity of inflammation, and NE was related to the severity of liver dysfunction.

Penehyclidine hydrochloride protects against lipopolysaccharide-induced acute lung injury by promoting the PI3K/Akt pathway.

Acute lung injury (ALI) attracted attention among physicians because of its high mortality. We aimed to determine whether the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway is involved in the protective effects of penehyclidine hydrochloride (PHC) against lipopolysaccharide (LPS)-induced ALI. H&E staining was used to observed pathological changes in the lung tissues. ELISA was used to evaluate the concentration of inflammatory mediators in the bronchoalveolar lavage fluid (BALF). White-light microscopy was performed to observe the TUNEL-positive nuclei. The viability of NR8383 alveolar macrophages was determined by using CCK-8. The levels of MPO, MDA, SOD, and GSH-Px were analyzed using ELISA kits. Western blotting was used to evaluate the ERS-associated protein levels and the phosphorylation of PI3K and Akt. PHC administration defended against LPS-induced histopathological deterioration and increased pulmonary edema and lung injury scores, while all of these beneficial effects were inhibited by LY. In addition, PHC administration mitigated oxidative stress as indicated by decreases in lung myeloperoxidase (MPO) and malondialdehyde (MDA) concentrations, and increases in glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) concentrations. It also alleviated LPS-induced inflammation. PHC administration attenuated apoptosis-associated protein levels, improved cell viability, and decreased the number of TdT-mediated dUTP Nick-End Labeling (TUNEL)-positive cells. Furthermore, PHC inhibited ERS-associated protein levels. Meanwhile, the protection of PHC against inflammation, oxidative stress, apoptosis, and ERS was inhibited by LY. Moreover, PHC administration increased PI3K and Akt phosphorylation, indicating that the upregulation of the PI3K/Akt pathway, while this pathway was inhibited by LY. PHC significantly activates the PI3K/Akt pathway to ameliorate the extent of damage to pulmonary tissue, inflammation, oxidative stress, apoptosis, and ERS in LPS-induced ALI.

Fabrication of CdS quantum dots with egg white and application in the assay of hypochlorous acid and myeloperoxidase activity and inhibition.

The myeloperoxidase (MPO)/H2O2-Cl- enzymatic reaction system and its product hypochlorous acid (HOCl) are closely related to many disease processes, and new methods to detect the levels of HOCl and MPO are being focused on. MPO is the only known enzyme for the catalytic production of HOCl in biological systems; therefore, monitoring the HOCl levels is a selective and direct readout of MPO activity. This study reported a simple and efficient fluorescence assay of HOCl and MPO activity and inhibition. Highly fluorescent CdS quantum dots (CdS QDs) were prepared in one pot where NaOH-pretreated egg white served as a stabilizer. These CdS QDs exhibit strong green emission centered at ca. 550 nm and enable rapid and selective fluorescence response to HOCl with a linear detection range of 8.0-250 μM and a limit of detection (LOD) of 2.5 μM. Moreover, the CdS QDs were further applied for sensing MPO based on the fluorescence quenching exerted by its reaction product HOCl. Detection of MPO is accomplished with a linear range from 0.1 to 40 mU mL-1 (1 U is the MPO concentration for catalysis of 1 micromolar substrate per minute) and a LOD of 0.06 mU mL-1. The developed synthesis method can be applied to large-scale synthesis of CdS QDs, and the strategy to sense HOCl and MPO activity and inhibition has potential biomedical applications such as clinical diagnosis and drug screening.

Airway neutrophils and myeloperoxidase in asthma patients with cold-induced bronchoconstriction

Introduction. The role of neutrophil inflammation of the bronchi in patients with asthma in the devel­opment and manifestation of cold airway hyperresponsiveness (CAHR) has not been sufficiently studied.Aim. To assess the level of neutrophils and the activity of myeloperoxidase (MPO) in the bronchi of asthma patients with cold-induced bronchospasm.Materials and methods. In 138 patients with mild-to-moderate asthma with CAHR, the level of asthma control (ACT), lung function (FEV1), cellular composition of sputum was examined before and after the bronchoprovo­cation test by isocapnic hyperventilation with cold air (IHCA). In sputum samples, the percentage of neutrophils, eosino­phils, and bronchial epithelial cells (structurally intact cylindrical ciliated and goblet cells) was assessed; the concentration and activity of MPO in neutrophils were studied by the cytochemical method.Results. The patients were divided into three groups: group 1 (n=94) - patients with mild cold-induced bronchospasm, group 2 (n=28) - with moderate broncho­spasm, group 3 (n=16) - with severe bronchospasm (AFEV1=- 13.5±0.3, -24.6±0.5, -36.9±1.5%, respectively). Patients did not differ in the level of asthma control (16 [12; 21]; 16 [13; 20] and 16 [12; 21] ACT points, respectively). Patients of the third group had lower values of bronchial patency in comparison with the first and second groups: FEV1 79.4±3.2; 92.4±1.7 (p&lt;0.01); 92.1±2.9% and FEF25-75 46.4±4.3; 66.1±2.5 (p&lt;0.001); 63.2±4.0% (p&lt;0.01). In sputum after the IHCA test in groups 2 and 3, an increase in the number of neutrophils was recorded from 35.5±3.9 to 46.0±3.8% (p&lt;0.05) and from 39.0±3.8 to 52, 4±4.4% (p&lt;0.05), respectively, while the number of neutrophils in group 1 did not change (43.2±2.4 and 44.3±2.1%). The concentration of MPO in response to the IHCA test in all groups significantly increased by more than 30% (p&lt;0.05).Conclusion. The mobilization of neutrophils in a mixed pattern of airway inflammation in asthma pa­tients is associated with worsening of cold-induced bronchospasm. An increase in the content of MPO in neutrophil gran­ules in response to the action of cold air is aimed at enhancing the secretion of the enzyme in the interstitium, activating its oxidative activity in the respiratory tract, and escalating the oxidative/halogenating stress that accompanies broncho­spasm.

Associations between myeloperoxidase and paraoxonase-1 and type 2 diabetes in patients with ischemic heart disease

BackgroundThe phrase “dysfunctional high-density lipoprotein” has been developed in the literature to describe the particle which loses its basic role- anti-oxidative and anti-inflammatory activity. In this porcess, the significance of enzymes- pro-oxidant myeloperoxidase (MPO) and antioxidant paraoxonase-1 (PON-1) from the perspective of HDL-C function has been noted.AimsThe objective of this study was to analyze the associations between two enzymes –MPO and PON-1 and type 2 diabetes (T2DM) in patients with ischemic heart disease (IHD).MethodsAn observational cross-sectional study including 70 patients with IHD of whom 35 had also T2DM, and 35 had no T2DM. Laboratory tests (MPO, PON-1, fasting glucose, glycated hemoglobin, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and high-sensitivity C-reactive protein) were performed.ResultsThe study revealed a significant difference in the serum concentration of the enzymes between patients with IHD with and without T2DM. Our results showed increased MPO concentration levels in diabetic patients. The analysis also revealed that T2DM is independently associated with an increase in MPO levels. Simultaneously, a decrease in PON-1 levels was observed in patients with T2DM. The study also revealed that T2DM is independently associated with a decrease in PON-1 levels.ConclusionsIn patients with type 2 diabetes the profile of enzymes involved in high-density lipoprotein metabolism in patients with IHD is worse than in patients without T2DM. The increase in the levels of MPO, an enzyme with oxidative and atherogenic properties and on a decrease in PON-1 levels, an enzyme with antioxidant and atheroprotective properties is observed.

Leisure-time regular exercise and prevention of the side effects of immune system activity in middle-aged healthy subjects

Regular exercise is recommended to improve immune system function and antioxidant activity, while conversely, it may cause inflammation by increasing neutrophil-derived main enzyme, myeloperoxidase, which produces reactive oxygen species. The present study aimed to investigate changes in myeloperoxidase level, its influence on total oxidant status, and the capacity of the antioxidant defence system to counteract oxidative stress in middle-aged men participating in leisure-time regular exercise compared to untrained peer subjects. Twenty trained (age 53.58±2.94 years, body mass index (BMI) 25.47±1.6) and 17 untrained (age 54.17±2.83 years, BMI 27.83±1.12) healthy middle-aged men participated in this study [Rasht, Gilan, Iran]. Participants performed a modified Bruce treadmill test as a model of progressive exercise training. Blood samples were taken before, immediately after, and one hour after the end of the test. A mixed ANOVA and Bonferroni post hoc test was used for the analysis of variables. A significant difference was observed in myeloperoxidase levels between groups, while the trained group showed a significantly lower concentration than the untrained group (P&lt;0.018). This result was also consistent with the lower total oxidant status in this group (P&lt;0.001). Total antioxidant capacity changed significantly in both groups with higher concentration in the trained group (P&lt;0.001). The leisure-time regular exercise can reduce myeloperoxidase concentration and total oxidant status in healthy middle-aged men while increasing the total antioxidant capacity, which may potentially protect them from the side effects of immune system activity induced by exercise training.

Fermented Astragalus and its metabolites regulate inflammatory status and gut microbiota to repair intestinal barrier damage in dextran sulfate sodium-induced ulcerative colitis

Fermentation represents an efficient biotechnological approach to increase the nutritional and functional potential of traditional Chinese medicine. In this study, Lactobacillus plantarum was used to ferment traditional Chinese medicine Astragalus, the differential metabolites in the fermented Astragalus (FA) were identified by ultra-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-MS), and the ameliorating effect of FA on dextran sulfate sodium (DSS)-induced colitis in mice were further explored. The results showed that 11 differential metabolites such as raffinose, progesterone and uridine were identified in FA, which may help improve the ability of FA to alleviate colitis. Prophylactic FA supplementation effectively improved DAI score, colon length and histopathological lesion in DSS-treated mice. The abnormal activation of the intestinal immune barrier in mice was controlled after FA supplementation, the contents of myeloperoxidase (MPO) and IgE were reduced and the contents of IgA were increased. The intestinal pro-inflammatory factors TNF-α, IL-1β, IL-6, and IL-17 were down-regulated and the anti-inflammatory factors IL-10 and TGF-β were up-regulated, suggesting that FA can intervene in inflammatory status by regulating the balance of Th1/Th2/Th17/Treg related cytokines. In addition, FA supplementation modified the structure of the intestinal microbiota and enriched the abundance of Akkermansia and Alistipes, which were positively associated with the production of short-chain fatty acids. These microbes and their metabolites induced by FA also be involved in maintaining the intestinal mucosal barrier integrity by affecting mucosal immunity. We observed that intestinal tight junction protein and mucous secreting protein ZO-1, occludin, and MUC2 genes expression were more pronounced in mice supplemented with FA compared to unfermented Astragalus, along with modulation of intestinal epithelial cells (IECs) apoptosis, verifying the intestinal mucosal barrier repaired by FA. This study is the first to suggest that FA as a potential modulator can more effectively regulate the inflammatory status and gut microbiota to repair the intestinal barrier damage caused by colitis.

Myeloperoxidase as a Potential Biomarker of Acute-Myocardial-Infarction-Induced Depression and Suppression of the Innate Immune System.

While myeloperoxidase (MPO) serves as an indicator of both neutrophil and innate-immune-system function, the potential suppression of the innate immune system in patients with acute myocardial infarction (AMI)-induced depression might be evidenced by a decrease in MPO serum levels. The aim of this prospective study was to (1) determine whether serum concentrations of MPO vary immediately and 6 months after AMI and (2) to investigate whether MPO concentrations at the time of the AMI are significant predictors of AMI-induced depression and the depression-associated suppression of the innate immune system. A total of 109 AMI patients were assessed with the Hamilton Depression Scale (HAMD-17) immediately after admission to the hospital and 6 months later. The MPO status was assessed with serum samples, which were also collected immediately and 6 months after AMI. The depressive patients showed significantly lower MPO blood levels immediately and 6 months after the AMI compared to the patients without depression (ANCOVA: MPO (depression) F = 4.764, df = 1, p = 0.031). The baseline MPO was observed as a significant predictor (p = 0.027) of AMI-induced depression 6 months after AMI. MPO is a potential biomarker for AMI-induced depression, indicating a depression-associated suppression of the innate immune system.

Regulation of radiation-induced liver damage by modulation of SIRT-1 activity: In vivo rat model.

Silent information regulator 1 (SIRT-1), a nicotinamide adenine dinucleotide-dependent deacetylase, was found to regulate cell apoptosis, inflammation, and oxidative stress response in living organisms. Therefore, the role of SIRT-1 in regulating forkhead box O/poly ADP-ribose polymerase-1 (FOXO-1/PARP-1) signaling could provide the necessary validation for developing new pharmacological targets for the promotion or inhibition of SIRT-1 activity toward radiation sensitivity. In the present study, the SIRT-1 signaling pathway is being investigated to study the possible modulatory effect of resveratrol (RSV, SIRT-1 activator) versus nicotinamide (NAM, SIRT-1 inhibitor) in case of liver damage induced by whole-body gamma irradiation. Rats were exposed to 6 Gy gamma radiation after being pretreated with either RSV (10 mg/kg/day) or NAM (100 mg/kg/day) for 5 days, and subsequent examining hepatic morphological changes and apoptotic markers were assessed. The expression of SIRT-1, FOXO-1, and cleaved PARP-1 in the liver was analyzed. RSV improved radiation-induced apoptosis, mitochondrial dysfunction, and inflammation signified by low expression of caspase-3, lactate dehydrogenase, complex-I activity, myeloperoxidase, and total nitric oxide content. RSV increased the expression of SIRT-1, whereas cleaved PARP-1 and FOXO-1 were suppressed. These protective effects were suppressed by inhibition of SIRT-1 activity using NAM. These findings suggest that RSV can attenuate radiation-induced hepatic injury by reducing apoptosis and inflammation via SIRT-1 activity modulation.