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ABSTRACT Objective Methods Results Conclusions To investigate serum, placental levels of active‐matrix metalloproteinase‐8 (aMMP‐8), myeloperoxidase (MPO) in preterm‐birth with/without pre‐eclampsia and term counterparts in relation with clinical periodontal parameters.Clinical periodontal measurements were recorded. Serum and placenta samples were collected during 173 full‐term (FT), pre‐term (PT) or pre‐term complicated by pre‐eclampsia (PTPE) deliveries. aMMP‐8 levels were measured by IFMA. MPO levels in the serum and placenta samples were determined by ELISA. Data were tested using non‐parametric tests.PTBE group exhibited higher full‐mouth probing depth and clinical attachment loss values than the other two groups (p < 0.05). Percentages of sites with plaque and bleeding on probing were lower in the PTBE group than in the other groups (p < 0.05). Serum aMMP‐8 and MPO concentrations were higher in PTPE group than in the other groups (p < 0.05). Placenta aMMP‐8 level was higher in the control group than in the PTPE group (p < 0.05). There was no significant difference between the groups in the placenta MPO levels (p > 0.05).Within the limits of this cross‐sectional study, it may be suggested that serum aMMP‐8 and MPO concentrations together with placenta aMMP‐8 levels may be associated with and reflect adverse pregnancy outcomes. Clinical periodontal findings did not reveal significant associations with these proteolytic and oxidative biomarkers. [ABSTRACT FROM AUTHOR]

AbstractThis study aimed to evaluate the protective potential of taurine (Tau) and enzymatically modified isoquercitrin (EMIQ), both individually and in combination, against MTX-induced cardiotoxicity in male rats. A total of 36 rats were randomly divided into six groups (six animals each): control (vehicle), MTX alone (20 mg/kg, single dose), EMIQ+MTX (EMIQ at 26 mg/kg, p.o. for 16 days, with a single dose of MTX on the 13th day), Tau + MTX (Tau at 500 mg/kg, p.o. for 16 days, with a single dose of MTX on the 13th day), (EMIQ+Tau)+MTX, and (EMIQ+Tau)½+MTX. MTX treatment resulted in elevated levels of cardiac creatine phosphokinase-myocardial band, troponin I, nitric oxide, malondialdehyde, and serum IL-6, while decreasing levels of cardiac myeloperoxidase, catalase, and superoxide dismutase. MTX also reduced expression of BMI-1, induced DNA laddering and fragmentation, and increased cleaved caspase-3 protein expression in cardiac tissue. Both Tau and EMIQ showed equivalent effectiveness in protecting the heart against MTX-induced damage due to their antioxidant, anti-inflammatory, and antiapoptotic properties. Notably, combined treatment with half-doses of Tau and EMIQ offered superior protection compared to full doses of each agent alone. The full-dose combination showed similar efficacy to the half-dose combination, with a few exceptions. Overall, these results suggest a synergistic effect of Tau and EMIQ in mitigating MTX-induced cardiotoxicity, warranting further investigation into the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: While COVID-19 has been controlled and deaths have decreased, the long-term consequences of COVID-19 remain a challenge we face today. This study was conducted to determine the relationship between the apoptosis of lymphocyte cells with DNA damage and oxidative stress and the therapeutic and clinical outcomes of elderly patients with COVID-19. Methods: This study was conducted from April 2020 to May 2021 (the period of severe attacks of the epidemic peak of COVID-19) and September 2022 (the post-COVID-19 period). The study groups included elderly patients with COVID-19 hospitalized in the ICU and normal wards of the hospital as well as elderly patients with influenza. A polymerase chain reaction was used to check the validity of the studied diseases. The Annexin V/Propidium Iodide method was used to evaluate the level of apoptosis. Genotoxic effects and DNA damage were assessed by the comet assay method. Total antioxidant status (TAS), total oxidant status (TOS), and myeloperoxidase activity (MPO) were measured by photometric methods. Results: The highest level of apoptosis in peripheral blood lymphocytes and the highest level of DNA damage were observed at both times in the intubated-ICU and non-intubated-ICU groups. In all groups, there was a significant increase in peripheral blood lymphocyte apoptosis levels and DNA damage levels compared to the healthy control group (p < 0.01). The level of apoptosis and DNA damage decreased significantly in the post-COVID-19 period (p < 0.01). In the investigation of oxidative stress biomarkers, the oxidative stress index, including TOS and MPO levels, increased in patients (p < 0.01), and the TAS level decreased (p < 0.01). Conclusion: It shows that the apoptosis of lymphocyte cells, DNA damage, and oxidative stress can be effective in prognostic decisions and is a suitable predictor for diagnosing the condition of patients with viral infections such as COVID-19 and influenza. [ABSTRACT FROM AUTHOR]

Objectives Anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitides (AAV) are rare conditions characterized by inflammatory cell infiltration in small blood vessels, leading to tissue necrosis. While most patients with AAV present antibodies against either myeloperoxidase (MPO) or proteinase 3 (PR3), rare cases of dual positivity for both antibodies (DP-ANCA) have been reported, and their impact on the clinical picture remains unclear. The goal of this study was to investigate the clinical implications, phenotypic profiles and outcomes of patients with DP-ANCA. Methods A retrospective screening for DP-ANCA cases was conducted at Brest University Hospital's immunology laboratory (France), analysing ANCA results from March 2013 to March 2022. Clinical, biological, imaging, and histological data were collected for each DP-ANCA case. Additionally, a comprehensive literature review on DP-ANCA was performed, combining an artificial intelligence (AI)-based search using BIBOT software with a manual PUBMED database search. Results The report of our cases over the last 9 years and those from the literature yielded 103 described cases of patients with DP-ANCA. We identified four distinct phenotypic profiles: (i) idiopathic AAV (∼30%); (ii) drug-induced AAV (∼25%); (iii) autoimmune disease associated with a low risk of developing vasculitis (∼20%); and (iv) immune-disrupting comorbidities (infections, cancers, etc) not associated with AAV (∼25%). Conclusion This analysis of over a hundred DP-ANCA cases suggests substantial diversity in clinical and immunopathological presentations. Approximatively 50% of DP-ANCA patients develop AAV, either as drug-induced or idiopathic forms, while the remaining 50%, characterized by pre-existing dysimmune conditions, demonstrates a remarkably low vasculitis risk. These findings underscore the complex nature of DP-ANCA, its variable impact on patient health, and the necessity for personalized diagnostic and management approaches in these cases. [ABSTRACT FROM AUTHOR]

Abstract Invasive candidiasis (IC) is a notable healthcare-associated fungal infection, characterized by high morbidity, mortality, and substantial treatment costs. Candida albicans emerges as a principal pathogen in this context. Recent academic advancements have shed light on the critical role of exosomes in key biological processes, such as immune responses and antigen presentation. This burgeoning body of research underscores the potential of exosomes in the realm of medical diagnostics and therapeutics, particularly in relation to fungal infections like IC. The exploration of exosomal functions in the pathophysiology of IC not only enhances our understanding of the disease but also opens new avenues for innovative therapeutic interventions. In this investigation, we focus on exosomes (Exos) secreted by macrophages, both uninfected and those infected with C. albicans. Our objective is to extract and analyze these exosomes, delving into the nuances of their protein compositions and subgroups. To achieve this, we employ an innovative technique known as Proximity Barcoding Assay (PBA). This methodology is pivotal in our quest to identify novel biological targets, which could significantly enhance the diagnostic and therapeutic approaches for C. albicans infection. The comparative analysis of exosomal contents from these two distinct cellular states promises to yield insightful data, potentially leading to breakthroughs in understanding and treating this invasive fungal infection. In our study, we analyzed differentially expressed proteins in exosomes from macrophages and C. albicans -infected macrophages, focusing on proteins such as ACE2, CD36, CAV1, LAMP2, CD27, and MPO. We also examined exosome subpopulations, finding a dominant expression of MPO in the most prevalent subgroup, and a distinct expression of CD36 in cluster14. These findings are crucial for understanding the host response to C. albicans and may inform targeted diagnostic and therapeutic approaches. Our study leads us to infer that MPO and CD36 proteins may play roles in the immune escape mechanisms of C. albicans. Additionally, the CD36 exosome subpopulations, identified through our analysis, could serve as potential biomarkers and therapeutic targets for C. albicans infection. This insight opens new avenues for understanding the infection's pathology and developing targeted treatments.

In a deforming partially molten rock, melt concentrates into a grain‐scale melt pocket aligned at a preferred orientation (melt‐preferred orientation, or MPO). However, observing this texture alone provides limited information on the 3D orientation and geometry of these melt pockets, which are critical parameters for estimating permeability. Here, we modeled the MPO of experimentally deformed peridotites by simulating melt streaks arising from melt pockets of various shapes and 3D orientations. The model aims to identify 3D distribution and characteristics of melt pockets that could account for the observed length, thickness, and the probability of melt streaks. Results show that melt pockets at preferred orientation exhibit greater length, thickness, and number density compared to those perpendicular. These results can be incorporated into the simulation of melt flow through individual melt pockets, which allows us to estimate the permeability corresponding to the observed MPO. We found that the permeability of vertically compressed peridotites increases with increasing compressive strain and a more elongated and thickened shape for melt pocket aligned at preferred orientation. The vertical permeability in the sample with 30% compressive strain is at least 40 times larger than that of an undeformed sample. For peridotites deformed under simple shear, the permeability exhibits an anisotropy of at least three. Such anisotropic permeability, coupled with the formation of melt‐rich bands and other melt channels, is believed to cause lateral melt focusing beneath mid‐ocean ridges. Plain Language Summary: The distribution of melt at the grain scale controls the permeability in partially molten rock. While observe melt streaks on thin sections show variations in length and thickness with respect to the orientation, the geometry and distribution of melt pockets in 3D are poorly constrained. Here, we use an improved statistical model to identify the dependence of melt pocket dimensions as functions of orientation. We further calculate melt flux through individual melt streaks and estimate permeability corresponding to the observed melt distribution texture. We found that deformation in the mantle can significantly accelerate melt extraction and potentially bend the melt flow using anisotropic permeability. Key Points: We parameterized the 3D shapes and orientations of melt pockets under the constraints of observed melt‐preferred orientation (MPO)Permeability in peridotites deformed under vertical compression increases with compressive strain and demonstrates anisotropy up to twoPermeability in peridotites deformed under simple shear demonstrates anisotropy of at least three [ABSTRACT FROM AUTHOR]

Background: An autoimmune disease that impacts both articular and extra-articular organs (e.g., eye, skin, and nervous system), progressive systemic rheumatoid arthritis (RA) is a pathological condition. We aimed to measure the serum level of neutrophil extracellular traps (NETs) in RA patients and to detect the correlation between NET level and RA activity. Also to study the relation between NET level and cardiovascular affection in RA patients by measuring the carotid intima media thickness. Patients and methods: This study was conducted on 50 RA patients diagnosed according to the American College of Rheumatology and European League Against Rheumatism 2010 diagnostic criteria for RA, and 50 apparently healthy volunteers matched with patients in sex and age for evaluation of the NET level. All patients underwent the following: full clinical assessment, laboratory investigations, radiographic assessment and wrist and measurement of carotid intima media thickness by ultrasound. Results: There was elevation in total cholesterol, triglycerides, LDL levels and reduction in HDL level in patients. There was increased level of MPO level in RA patients' group with significant difference between the RA and control group (P<0.05). There was significant positive correlation between MPO level and clinical, laboratory and radiological findings of the patients (P<0.05). Conclusion: The serum level of NETs is increased in RA patients and correlated with rheumatoid disease activity detected by MSUS and DAS -28. Also, the serum level of NETs could be considered a useful biomarker for the early prediction of subclinical atherosclerosis and cardiovascular affection in RA patients. [ABSTRACT FROM AUTHOR]

Background: Prevention and treatment of the monkeypox virus (Mpox) remain challenging in areas where it is endemic. This systematic review and meta-analysis aimed to collect this information from various studies in one study to give a comprehensive view of people's opinions, fears, and behaviors about this virus. Methods: We searched PubMed, Scopus, Web of Science, the Cochrane Library, and Google Scholar for descriptive cross-sectional study designs conducted in 2022 and 2023 addressing knowledge, attitude, perception, preparedness, willingness to get vaccinated, and practices against Mpox infection. Results: Among the included studies, 16 studies assessed the level of knowledge of study participants regarding Mpox with a total of 9066 participants. Among them, 4222 (46.6 %) were reported to have good knowledge, and 4844 (53.4%) were reported to have poor knowledge about Mpox. Regarding willingness to get vaccinated against Mpox, 14 studies with a total of 10,696 participants were included. Among them, 7006 (65 %) were willing to get vaccinated while 3690 (35 %) weren’t willing to be vaccinated. Conclusion: Knowledge about Mpox should be increased and awareness should be spread regarding the importance of preventive measures such as vaccination to protect the population from another COVID-19-like pandemic.

AimsNeutrophils and neutrophil extracellular traps (NETs) play multifaceted roles in inflammatory diseases. If the balance of NET formation and clearance is disturbed, they contribute to the development and pathogenesis of a plethora of inflammatory diseases. They promote inflammation and tissue degradation, and occlude vessels and ducts. This study focused on the presence of NET remnants generated during the clearance by nucleases and phagocytes.MethodsNET associated parameters in serum and plasma samples from various pathological conditions were investigated. We performed fluorescence-based assays to analyze the concentration of cell free DNA and the activity of neutrophil elastase. The presence of citrullinated histone H3, as well as neutrophil elastase- or myeloperoxidase-DNA complexes were examined employing enzyme-linked immunosorbent assays.ResultsWe analyzed samples from a variety of inflammatory conditions: (I) the rheumatic autoimmune diseases systemic lupus erythematosus, rheumatoid arthritis, and primary Sjögren’s syndrome (II) the inflammatory bowel diseases ulcerative colitis and Crohn’s disease (III) hidradenitits suppurativa and (IV) the viral-induced pathologies Coronavirus disease 2019 (COVID-19), and Post COVID Syndrome (PCS). While most NET associated parameters were detected in all inflammatory conditions, certain markers displayed disease-specific patterns. We compared the markers in terms of the concentration, correlations with each other and to disease activity, and their impact on sample variability. Systemic lupus erythematosus and rheumatoid arthritis were associated with increased levels of cell free DNA, and citrullinated histone H3 as well as neutrophil elastase-activity, respectively. Samples from patients with COVID-19 were characterized by elevated levels of neutrophil elastase- and myeloperoxidase-DNA complexes.ConclusionDifferent diseases are linked to characteristic patterns of NET associated parameters. These patterns offer insights into aberrant NET formation and clearance in different pathologies and may represent key targets for treatment development.

Hypertensive disorders of pregnancy (HDP) are multifaceted syndromes unique to pregnancy, characterized by increased blood pressure, edema, and proteinuria. Patients with HDP exhibit signs of endothelial dysfunction, possibly linked to increased myeloperoxidase (MPO) level and aberrant oxidative stress. Additionally, altered level of tissue inhibitor of metalloproteinase-1 (TIMP1) protein is associated with placental ischemia, hypoxia, and maternal vascular endothelial damage. Preeclampsia (PE) represents a critical stage of HDP that poses severe threats to maternal and fetal safety. This study aimed to determine the relationship between MPO and TIMP1 polymorphisms and the risk of PE in the Chinese Han population. Single nucleotide polymorphisms (SNPs), including MPO rs7208693, MPO rs2243828, and TIMP1 rs6609533, were genotyped in 170 patients with PE and 303 control participants. No significant association was observed between MPO polymorphisms (rs7208693 and rs2243828) and the risk of PE, whereas significant association between the TIMP1 rs6609533 A > G SNP and PE susceptibility was found. Specifically, individuals with the GG or AG genotypes had elevated risk of PE compared to those harboring the AA genotype. Furthermore, in the PE group, patients carrying the G allele were more likely to experience fetal growth restriction (FGR). In the non-PE group, the association between the G allele and the risk of FGR was not evident. In conclusion, the TIMP1 rs6609533 G allele in Chinese Han women was identified as a risk factor for PE. Our results indicated that the TIMP1 rs6609533 SNP can serve as a biomarker for the clinical diagnosis and treatment of PE.

Background and Aims: Peroxidase deficiency is one of the commonly inherited phagocytic defects. It has been also found to exist as a transient phenomenon in association with some clinical conditions. But that it can interfere and cause erroneous automated differential WBC count is something which is not commonly known. Materials and methods: Complete blood counts were analysed using Advia 2120i and Coulter DXH 900 haematology analysers and manually reviewed on peripheral blood smear stained with Leishman stain. Results: Peroxidase deficiency in neutrophils and eosinophils resulted in them getting counted as monocytes by the analyser causing pseudomonocytosis, pseudoneutropenia and pseudoeosinopenia. These were detected by a slide review and by reanalysing the samples on an analyser which worked on a different principle. Conclusion: There is a need to confirm monocytosis given by analysers working on the peroxidase principle with an alternate method. This will prevent needless medical investigations for pseudoneutropenia, pseudoeosinopenia and persistent monocytosis, thus preventing unwarranted mental agony and financial burden to patients. It also helps to save the laboratory's reputation. A careful review of instrument flags not only helps reach an accurate result but sometimes they can also aid in the diagnosis of a rare potential genetic disorder like MPO deficiency. [ABSTRACT FROM AUTHOR]

Abstract In a deforming partially molten rock, melt concentrates into a grain‐scale melt pocket aligned at a preferred orientation (melt‐preferred orientation, or MPO). However, observing this texture alone provides limited information on the 3D orientation and geometry of these melt pockets, which are critical parameters for estimating permeability. Here, we modeled the MPO of experimentally deformed peridotites by simulating melt streaks arising from melt pockets of various shapes and 3D orientations. The model aims to identify 3D distribution and characteristics of melt pockets that could account for the observed length, thickness, and the probability of melt streaks. Results show that melt pockets at preferred orientation exhibit greater length, thickness, and number density compared to those perpendicular. These results can be incorporated into the simulation of melt flow through individual melt pockets, which allows us to estimate the permeability corresponding to the observed MPO. We found that the permeability of vertically compressed peridotites increases with increasing compressive strain and a more elongated and thickened shape for melt pocket aligned at preferred orientation. The vertical permeability in the sample with 30% compressive strain is at least 40 times larger than that of an undeformed sample. For peridotites deformed under simple shear, the permeability exhibits an anisotropy of at least three. Such anisotropic permeability, coupled with the formation of melt‐rich bands and other melt channels, is believed to cause lateral melt focusing beneath mid‐ocean ridges.

The association between MPO-ANCA-associated vasculitis (AAV) and interstitial lung disease (ILD) has been well established. Pulmonary fibrosis may coexist with, follow, or even precede the diagnosis of AAV, and its presence adversely affects the prognosis. The optimal approach to investigating ANCA in patients with ILD remains a subject of ongoing debate. Here we aim to describe presentation and progression of MPO-ANCA ILD. We conducted a retrospective evaluation of a cohort of individuals diagnosed with MPO-ANCA ILD, with or without accompanying renal impairment, at the Immunology and Cell Therapy Unit, Careggi University Hospital, Florence, Italy, between June 2016 and June 2022. Clinical records, imaging studies, pathologic examinations, and laboratory test results were collected. Among the 14 patients identified with MPO-ANCA ILD, we observed a significant association between MPO-ANCA titers assessed at the time of ILD diagnosis and renal involvement. Renal impairment in these cases often manifested as subclinical or slowly progressive kidney damage. Interestingly, complement C3 deposits were consistently found in all renal biopsy specimens, thereby suggesting the potential for novel therapeutic targets in managing renal complications associated with MPO-ANCA ILD. The presentation of MPO-ANCA vasculitis as ILD can be the first and only clinical manifestation. MPO-ANCA levels at ILD diagnosis could warn on the progression to renal involvement in patients with MPO-ANCA ILD, hence caution is needed because renal disease can be subclinical or smoldering.

Backgrounds Venous Thromboembolism (VTE) is a disease entity comprising Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). VTE events increase the mortality rate of patients with cancer receiving platinum-based chemotherapy. Soluble P-Selectin, Neutrophil Extracellular Traps (NET), and myeloperoxidase (MPO) are risk factors associated with DVT in malignancy patients receiving platinum-based chemotherapy. The purpose of this study was to determine the role of soluble P-selectin, NET, and MPO as risk factors for DVT in patients with malignancy receiving platinum-based chemotherapy. Patients and Methods This study used a case-control design (matched pair case-control study) based on age and gender. The case group consisted of subjects with DVT, whereas the control group consisted of subjects without DVT. The subjects were 31 in each case and control groups. Soluble P-selectin, NET, and MPO levels were measured in each group. Results The mean age of case group was 50.26±12.15 years meanwhile in control group was 52.81±11.64 years. In the case group, 71% of the subjects were female, whereas 51.6% of the control group were male. Most subjects, either in the case group (71%) or the control group (71%), used carboplatin. In the case group, cervix malignancy was the most common malignancy (32.3%), whereas in the control group, it was nasopharyngeal malignancy (25.8%). High soluble P-selectin level was a risk factor for DVT (OR 3.38, CI 1.180 – 9.780, p=0.02). A high NET level was also a risk factor for DVT (OR 2.88, CI 1.026-8.074, p=0.04). The high MPO levels in this study could not be proven as a risk factor. Conclusions Soluble P-selectin and NET are risk factors that play a role in the pathophysiology of DVT through the pathomechanism of immunothrombosis induced by endothelial injury and activation of monocytes and neutrophils due to the use of platinum-based chemotherapy.

Purpose: Myeloperoxidase (MPO) has been identified as a mediator in various inflammatory diseases. Bacterial infection of the intestine and hypoxia can both lead to inflammatory responses, but the role of MPO in these phenomena remains unclear. Methods: By building the MPO-/- mice, we evaluated relevant inflammatory factors and tissue damage in mice with intestinal Citrobacter rodentium infection and hypoxia. The body weight and excreted microorganisms were monitored. Intestinal tissues were collected 7 days after bacterial infection under hypoxia to undergo haematoxylin-eosin staining and assess the degree of pathological damage. ELISA assays were performed to quantify the serum levels of TNF-α, IFN-γ, IL-6, and IL-1β inflammatory cytokines. PCR, WB, and IF assays were conducted to determine the expression of chemokines MCP1, MIP2, and KC in the colon and spleen. Results: The C. rodentium infection and hypoxia caused weight loss, intestinal colitis, and splenic inflammatory cells active proliferation in wild-type mice. MPO deficiency alleviated this phenomenon. MPO-/- mice also displayed a significant decline in bacteria clearing ability. The level of TNF-α in the serum and spleen was both lower in MPO-/- hypoxia C. rodentium-infected mice than that in wild-type mice. The chemokines expression levels of MIP2, KC, and MCP1 in the spleen and colon of each bacterial infected group were significantly increased (p < .05), while in hypoxia, the factors in the spleen and colon were decreased (p < .05). MPO deficiency was found to lower the levels of these chemokines compared with wild-type mice. Conclusion: MPO plays an important role of the inflammatory responses in infectious enteritis and hypoxia in mice, and the loss of MPO may greatly reduce the body's inflammatory responses to fight diseases. [ABSTRACT FROM AUTHOR]

Background: Members of beta blockers drugs possess significant antioxidant activities. The current research is to assess the effect of the labetalol on acetic acid (AA-induced) colitis in rat model. Methods: Forty adult Wistar rats were separated into 4 groups, including the negative control group, AA group, AA + sulfasalazine (100 mg/kg/day) group, and AA + labetalol (300 mg/kg/day) group. Colitis was induced in rats by the inter-rectal installation of 2 mL of 4% (v/v) AA. Sulfasalazine and labetalol were administered orally for 7 days after 2 hours of induction. The following parameters were measured: disease activity index (DAI), histopathological changes and colon tissue homogenate concentrations of proinflammatory mediators IL-1ß, adhesion molecules ICAM-1, and oxidative stress marker myeloperoxidase (MPO). Results: The treatment with labetalol significantly reduced DAI and histopathological changes induced by AA. Also, labetalol markedly decreased the concentrations of IL-1ß, ICAM-1, and MPO in colonic tissue that were increased by AA. The effects of labetalol were significantly lower than that produced by sulfasalazine as standard drug. Conclusions: Labetalol exerts ameliorative effects on disease activity and histopathological features of AA-induced colitis in rats possibly through antioxidant effects and inhibition of inflammatory mediators. [ABSTRACT FROM AUTHOR]

Background and Objectives: Inflammation and dysregulation in the intestinal barrier function in acute pancreatitis (AP) trigger pancreatic lesions, systemic inflammatory response, and multiple organ dysfunction. Eugenol, as the main component of clove (Syzygium aromaticum), is known for its antioxidant and anti-inflammatory properties. We studied the potentially beneficial effect of eugenol in a rodent model of biliopancreatic duct ligation-induced AP. Materials and Methods: Rats were randomly divided into three groups: Sham, AP, and AP + eugenol (15 mg/kg/day). Serum TNFα, IL-6, IL-18, and resistin levels, as well as IL-6, TNFα, MPO, HMGB1, and CD45 tissue expression, were determined at various timepoints after the induction of AP. Results: Eugenol attenuated hyperemia and inflammatory cell infiltration in the intestinal mucosal, submucosal, and muscular layers. IL-6 and resistin serum levels were significantly reduced in the AP + eugenol group, while serum TNFα and IL-18 levels remained unaffected overall. TNFα pancreatic and intestinal expression was attenuated by eugenol at 72 h, while IL-6 expression was affected only in the pancreas. MPO, CD45, and HMGB1 intestinal expression was significantly reduced in eugenol-treated rats. Conclusions: Eugenol managed to attenuate the inflammatory response in the intestine in duct ligation-induced AP in rats. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to better understand the link between SARSCoV-2 infection and autoimmune rheumatic diseases (ARDs) development by analyzing blood samples from 200 registered participants, and measuring biomarkers, such as cell-free DNA, MPO (myeloperoxidase), cathepsin S, and complement type 2 receptor. PATIENTS AND METHODS: Blood samples were collected from 200 participants (100 females and 100 males; age range: 17-55 years). Participants were divided into five groups based on their COVID-19, SARS-CoV-2 nucleocapsid-specific IgG, and COVID-19 vaccination status. The Enzyme-Linked Immunosorbent Assay (ELISA) was used to identify the biomarkers. RESULTS: ANOVA and t-tests revealed that the group of COVID-19 positive, SARS-CoV-2 nucleocapsid-specific IgG negative, and non-vaccinated individuals had the greatest average value for cathepsin S (p = 0.03). This suggests a correlation between the presence of COVID-19 and autoimmune disorders. The group with the greatest average value of cellfree DNA was the COVID-19-negative, SARSCoV-2 nucleocapsid-specific IgG-negative, vaccinated group (p = 0.03). This may suggest that even though they had not contracted the disease, they may have had a stronger immune response to the virus since vaccines can stimulate an immune response even in individuals who have not been infected by the virus. Furthermore, the SARS-CoV-2 nucleocapsid-specific IgG+ and COVID-19 positive groups had higher levels of myeloperoxidase, a neutrophil protein linked to inflammation and tissue damage, suggesting a higher risk of autoimmune rheumatologic illnesses (p = 0.02). CONCLUSIONS: The study suggests a correlation between COVID-19 status and the development of autoimmune disorders, as well as a potential link between a COVID-19 infection and a strong immune response. However, this study had limitations – the selection of participants and a small sample size, which offers potential for further research and examination. [ABSTRACT FROM AUTHOR]

Infection remains current as an important discussion topic in the etiological factors of atherosclerosis. Ischemic-modified albumin (IMA), galectin-3 (gal-3), paraoxonase-1 (PON-1), and myeloperoxidase (MPO) are biomolecules that play an important role in the pathogenesis of atherosclerosis. Our aim is to investigate serum IMA, gal-3, PON-1, and MPO activity in acute brucellosis infection. Forty patients with acute brucellosis and 40 healthy individuals were included in the study. Serum IMA, gal-3, PON-1, and MPO activity were analyzed by the ELISA method. In acute brucellosis infection, serum gal-3, IMA, and MPO activities were found to be significantly increased compared to the control group, and PON-1 activity was found to be significantly decreased compared to the control group (p < 0.001). There was a positive correlation between serum IMA, and MPO activity (r = 0.707 p = 0.000) and a negative correlation (r = −0.943, p = 0.000) between PON-1 activity. There was a positive correlation between serum gal-3 and MPO activity (r = 0.683, p = 0.000) and IMA level (r = 0.927, p = 0.000) and a negative correlation between PON-1 activity (r = −0.951, p = 0.000). Conclusion, it was found that serum gal-3, IMA levels and MPO activity increased, while PON-1 activity decreased. These results showed that the oxidant-anti-oxidant balance is impaired in acute brucellosis infection. In addition, these results indicate that brucella infection may be increase the risk of atherosclerosis. Further studies are needed to support our findings. [ABSTRACT FROM AUTHOR]

Abstract Background Anatabine, although being one of four major tobacco alkaloids, is never accumulated in high quantity in any of the naturally occurring species from the Nicotiana genus. Previous studies therefore focused on transgenic approaches to synthetize anatabine, most notably by generating transgenic lines with suppressed putrescine methyltransferase (PMT) activity. This led to promising results, but the global gene expression of plants with such distinct metabolism has not been analyzed. In the current study, we describe how these plants respond to topping and the downstream effects on alkaloid biosynthesis. Results The surge in anatabine accumulation in PMT transgenic lines after topping treatment and its effects on gene expression changes were analyzed. The results revealed increases in expression of isoflavone reductase-like (A622) and berberine bridge-like enzymes (BBLs) oxidoreductase genes, previously shown to be crucial for the final steps of nicotine biosynthesis. We also observed significantly higher methylputrescine oxidase (MPO) expression in all plants subjected to topping treatment. In order to investigate if MPO suppression would have the same effects as that of PMT, we generated transgenic plants. These plants with suppressed MPO expression showed an almost complete drop in leaf nicotine content, whereas leaf anatabine was observed to increase by a factor of ~ 1.6X. Conclusion Our results are the first concrete evidence that suppression of MPO leads to decreased nicotine in favor of anatabine in tobacco roots and that this anatabine is successfully transported to tobacco leaves. Alkaloid transport in plants remains to be investigated to higher detail due to high variation of its efficiency among Nicotiana species and varieties of tobacco. Our research adds important step to better understand pyrrolidine ring biosynthesis and its effects on gene expression and subsequent accumulation of anatabine.

Objectives The study aimed to evaluate the impact of aging on the formation of neutrophil extracellular traps (NETs). The impaired formation of NETs is the cause of an abnormal innate immune response. Material and Methods The study included a total of 45 healthy male subjects of different age groups. Whole blood was collected from the subjects, and the concentration of myeloperoxidase (MPO), the main biocidal protein in NETs, was determined in serum using ELISA. The serum levels of circulating free DNA (cfDNA), which are the structural basis of NETs, were also measured by fluorescence. In addition, the white blood cell count was determined, whole blood smear was evaluated, and the neutrophillymphocyte ratio was calculated. The variations in the levels of NET biomarkers were analyzed in different age groups. Results The low levels of MPO (243.70 ng/ml) and cfDNA (6.24 ng/100 μl) in boys indicated neutrophil insufficiency for NETosis in children. A progressive increase in the levels of MPO and cfDNA with age was observed among adolescents (420.91, p = 0.04; 13.55, p = 0.03, respectively), with the highest level noted in the healthy adult group (466.58, p = 0.01; 14.07, p = 0.01, respectively). The levels of the studied parameters were comparable in adolescents and young adults, which proved that the NETosis process was appropriate and suggested the attainment of neutrophil maturity for the release of NETs in adolescence. The levels of MPO and cfDNA were low in older men (225.46, p < 0.01; 5.19, p < 0.01, respectively) indicating impaired NET formation. Conclusions Data on the generation of NETs in different age groups obtained in this study can allow a better understanding of the ontogenesis of the immune system in terms of the course of NETosis, and also indicate the need to support nonspecific responses in children and adults. Further research should be performed to determine the possibility of regulating the NETosis process. Int J Occup Med Environ Health. 2023;36(3):333–48

The pathogenesis of inflammatory bowel diseases has not been fully studied, and the therapies used have side effects that limit their use.The purpose of this study is to conduct a clinical and immunological analysis of the effectiveness of vitamin D3 in the original rectal suppositories in experimental colitis (EC).EC was modeled with oxazolone. Original suppositories with vitamin D3 in group 3 and 5-ASA in group 4 were used per rectum. The clinic was evaluated on the Disease activity index scale. The expression of MPO and TNFa, the content of neutrophils, lymphocytes, eosinophils, histiocytes, plasmocytes, fibroblasts, ulcerative defect, tissue damage index were determined in the focus of colon injury. The study was carried out on days 2, 4 and 6.With EC, DAI increases for the entire day, MPO and TNFa increase in the lesion, ulcerative defect isfixed, neutrophil-lymphocytic infiltration increases, and TDI increases. When comparing the morphometric parameters of the alteration zone in EC under the conditions of vitamin D3 use, in contrast to the use of 5-ASA, a decrease in the number of lymphocytes, an increase in fibroblasts was revealed on day 2, a decrease in the number of plasmocytes and an increase in fibroblasts on day 4, an increase in the number of histiocytes and fibroblasts on day 6. The diameter of the ulcerative defect and the TDI index have no significant differences between the compared groups. When comparing the effectiveness of vitamin D3, in contrast to the use of 5-ASA, the MPO content is higher on day 6; the TNFa content is higher on day 4.In EC, the effects of using rectal suppositories with vitamin D3 on clinical signs, the size of the ulcerative defect, the content of MPO and TNFa in the lesion are comparable to the effects of using rectal suppositories with 50 mg of 5-ASA; more pronounced with respect to the dynamics of the cellular composition of the lesion of the colon.

BackgroundSeveral observational studies have investigated the association between myeloperoxidase (MPO) and obstructive sleep apnea (OSA). However, the nature of this relationship remains uncertain due to potential selection and confounding biases. To resolve this, we conducted a bidirectional two-sample Mendelian randomization (MR) study to scrutinize the causal relationship between MPO and OSA.MethodsInstrumental variables (IVs) for OSA were sourced from the publicly available FinnGen dataset, encompassing 38,998 OSA cases and 336,659 controls. Data on MPO were sourced from a study of 21,758 individuals conducted by the European Bioinformatics Institute (EBI). The primary MR analysis utilized the inverse-variance weighted (IVW) method, with MR–Egger intercept and leave-one-out methods assessing pleiotropy and Cochran’s Q test determining heterogeneity.ResultsThe IVW analysis indicated a causal relationship between heightened MPO levels and an increased incidence of OSA. Individuals with elevated MPO levels manifested a higher propensity to develop OSA, exhibiting an odds ratio (OR) of 1.075 and a 95% confidence interval (CI) of 1.011–1.143 (p = 0.021). Conversely, the reciprocal analysis unveiled no significant association between OSA and heightened MPO levels (p = 0.643). No directional pleiotropy was identified through the MR–Egger intercept test (p > 0.05).ConclusionOur study provides evidence of an association between elevated MPO levels and an increased incidence of OSA. However, OSA does not necessarily lead to elevated MPO levels. When patients present with high MPO levels, screening for OSA may be advisable, considering their clinical characteristics.

ABSTRACTObjectives: Infection remains current as an important discussion topic in the etiological factors of atherosclerosis. Ischemic-modified albumin (IMA), galectin-3 (gal-3), paraoxonase-1 (PON-1), and myeloperoxidase (MPO) are biomolecules that play an important role in the pathogenesis of atherosclerosis. Our aim is to investigate serum IMA, gal-3, PON-1, and MPO activity in acute brucellosis infection.Materials and Methods: Forty patients with acute brucellosis and 40 healthy individuals were included in the study. Serum IMA, gal-3, PON-1, and MPO activity were analyzed by the ELISA method.Results: In acute brucellosis infection, serum gal-3, IMA, and MPO activities were found to be significantly increased compared to the control group, and PON-1 activity was found to be significantly decreased compared to the control group (p

• 22q11.2 deletion syndrome is associated with a high prevalence of schizophrenia. • Inflammation and oxidative stress (OS) involve in schizophrenia's pathophysiology. • The relationship between OS, schizophrenia and 22q11.2DS has not been studied. • Individuals with 22q11.2DS had higher OS levels, compared to healthy controls. • PBMCs of individuals with 22q11.2DS were less resilient to the induction of OS. 22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans. This condition is associated with a wide range of symptoms including immune and neuropsychiatric disorders. Notably, psychotic disorders including schizophrenia have a prevalence of ∼ 30%. A growing body of evidence indicates that neuroinflammation and oxidative stress (OS) play a role in the pathophysiology of schizophrenia. In this study, we aim to assess the interaction between 22q11.2DS, OS and schizophrenia. Blood samples were collected from 125 participants (including individuals with 22q11.2DS [n = 73] and healthy controls [n = 52]) from two sites: Sheba Medical Center in Israel, and University Hospital Gasthuisberg in Belgium. Baseline OS levels were evaluated by measuring Myeloperoxidase (MPO) activity. A sub-sample of the Israeli sample (n = 50) was further analyzed to examine survival of Peripheral Blood Mononuclear Cells (PBMCs) following induction of OS using vitamin K3. The levels of MPO were significantly higher in all individuals with 22q11.2DS, compared to healthy controls (0.346 ± 0.256 vs. 0.252 ± 0.238, p =.004). In addition, when comparing to healthy controls, the PBMCs of individuals with 22q11.2DS were less resilient to induced OS, specifically the group diagnosed with psychotic disorder (0.233 ± 0.206 for the 22q11.2DS individuals with psychotic disorders, 0.678 ± 1.162 for the 22q11.2DS individuals without psychotic disorders, and 1.428 ± 1.359 for the healthy controls, p =.003, η2 = 0.207). Our results suggest that dysregulation of OS mechanisms may play a role in the pathophysiology of the 22q11.2DS phenotype. The 22q11.2DS individuals with psychotic disorders were more sensitive to induction of OS, but did not present significantly different levels of OS at baseline. These results may be due to the effect of antipsychotic treatment administered to this sup-group. By elucidating novel molecular pathways, early identification of biochemical risk markers for 22q11.2DS and psychotic disorders can be detected. This can ultimately pave the way to the design of early and more precise interventions of individuals with 22q11.2DS. [ABSTRACT FROM AUTHOR]

Tissue inflammation drives the infiltration of innate immune cells that generate reactive species to kill bacteria and recruit adaptive immune cells. Neutrophil activation fosters the release of myeloperoxidase (MPO) enzyme, a heme-containing protein generating hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride ions. MPO-dependent oxidant formation initiates bioactive oxidation and chlorination products and induces oxidative post-translational modifications (oxPTMs) on proteins and lipid oxidation. Besides HOCl and H2O2, further reactive species such as singlet oxygen and nitric oxide are generated in inflammation, leading to modified proteins, potentially resulting in their altered bioactivity. So far, knowledge about multiple free radical-induced modifications of MPO and its effects on HOCl generation is lacking. To mimic this multi-oxidant microenvironment, human MPO was exposed to several reactive species produced simultaneously via argon plasma operated at body temperature. Several molecular gas admixes were used to modify the reactive species type profiles generated. MPO was investigated by studying its oxPTMs, changes in protein structure, and enzymatic activity. MPO activity was significantly reduced after treatment with all five tested plasma gas conditions. Dynamic light scattering and CD-spectroscopy revealed altered MPO protein morphology indicative of oligomerization. Using mass spectrometry, various oxPTMs, such as +1O, +2O, and +3O, were determined on methionine and cysteine (Cys), and -1H-1N+1O was detected in asparagine (Asp). The modification types identified differed between argon-oxygen and argon-nitrogen plasmas. However, all plasma gas conditions led to the deamidation of Asp and oxidation of Cys residues, suggesting an inactivation of MPO due to oxPTM-mediated conformational changes. [ABSTRACT FROM AUTHOR]

Introduction: Severe forms of COVID-19, the disease caused by SARS-CoV-2, are characterized by acute respiratory distress syndrome, robust lung inflammation and death in some patients. Strong evidence has been accumulating that polymorphonuclear neutrophilic granulocytes (PMN) play an important role in the pathophysiology of severe COVID-19. SARS-CoV-2 directly induces in vitro PMN activation, mainly the release of neutrophil extracellular traps (NETs). However, the viral components inducing this PMN response remain unclear. Methods: In this work human PMN responses were assessed in vitro in response to the spike (S) protein of two different SARS-CoV-2 variants, anti-S IgG1 antibodies or immune complexes formed by them. Production of reactive oxygen species (ROS) was measured by Diogenes-based chemiluminescence. Release of myeloperoxidase (MPO) was assessed by ELISA while secretion of a list of cytokines and growth factors was determined by high-performance multiplex cytokine assay. Results and discussion: We show that the SARS-CoV-2 Omicron variant S protein and anti-spike IgG1, either alone or together, stimulate ROS production in human PMNs. We also observed that the SARS-CoV-2 Wuhan S protein and anti-S IgG1 antibody together triggerMPO release from PMNs. Based on the relevance of SARSCoV-2 and influenza co-infections, we have also investigated the impact of influenza virus infection on the previous PMN responses to S proteins or anti-S antibodies. We did not detect any significant effect of influenza co-infection on ROS generation in PMNs. Our data also show that PMN stimulation by S proteins induced the release of different chemokines, growth factors, regulatory and proinflammatory cytokines. Overall, our findings show that the SARS-CoV-2 S protein, an anti-spike IgG1 antibody or their immune complex, promote oxidative responses of PMNs in a variant-dependent manner, contributing to a better understanding of the role of PMN responses during SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: Most dynamic area of scientific investigation is to identify the bioactive compounds and establish their potential health effects against chronic diseases. Multi-targeted compounds with fewer side effects has shown to be potential therapeutic agents. Objectives: To evaluate the anti-inflammatory effect of isolated Squalene (SQ), a triterpenoid from Simarouba glauca in carrageenan-induced acute inflammation. Materials and Methods: Squalene (SQ), a triterpenoid fraction was isolated from Simarouba glauca and characterized by FT-IR and NMR. Experimental animals were categorized into five groups, group I was control (0.5% DMSO in normal saline), group II received Carrageenan (Carr), group III received SQ and Carr, whereas group IV received diclofenac and Carr. After 1 hr, SQ and diclofenac (20mg/kg) were administered (i.p.). Carrageenan suspension was injected into the sub-plantar tissue of the right hind paw. Paw edema was determined 3 hours post-carrageenan administration. Rats were sacrificed and mRNA expression of TNF-α and IL-6, levels of PGE-2 and TBARS, activities of COX-2, SOD, catalase, GPx, MPO, and the level of nitrite were measured. Results: SQ at a dose of 5.0 mg/kg body weight was found to be the minimal dose for maximum edema inhibition. Serum levels of TNF-α, IL-6, PGE-2, NO, COX-2 and levels of TBARS and MPO were significantly reduced (p < 0.05). Antioxidant markers such as SOD, Catalse and GPx were increased significantly (p < 0.05). Conclusion: These results suggest the anti-inflammatory properties of SQ and its multi-targeted mechanism of action, meriting its potential therapeutic efficacy in various inflammatory diseases. [ABSTRACT FROM AUTHOR]

Myeloperoxidase (MPO) has been reported in prostate tissue, and considering its pro-oxidant properties, this location might be linked to prostate pathology. The possibility that the glandular prostatic tissue might be the source of MPO and its potential inflammatory effects must be tested. Human prostate material was obtained from prostate biopsies and radical prostatectomies. Immunohistochemistry was performed using MPO-specific human antibody. In situ hybridization using MPO-specific probes and laser-assisted microdissection for quantitative real-time RT-PCR were performed to observe whether MPO is being produced in prostate tissue. Mass spectrometry on prostate biopsies was used to detect products of MPO activity in nucleic acids (DNA/RNA). MPO contribution to intracellular accumulation of ROS and interleukin-8 in prostatic epithelial cells was monitored in vitro. Immunohistochemistry confirmed cellular localization of MPO in epithelial cells of the prostate. The staining varied from light to high intensity. In situ hybridization did not address the presence of mRNA coding for MPO. No MPO-specific modifications on nucleic acids were detected. Mox-LDL was a major factor inducing ROS and cytokines production in prostatic epithelial cells. We did not demonstrate that MPO was synthetized by prostatic epithelial cells. However, in vitro experiments showed the ability of MPO to potentiate the ROS production and inflammation on prostate epithelial cells. Results do not allow us to demonstrate a role of MPO in prostate to date but further studies are mandatory to focus on the potential impact of MPO in the development of prostatic diseases. [ABSTRACT FROM AUTHOR]

Background: Anatabine, although being one of four major tobacco alkaloids, is never accumulated in high quantity in any of the naturally occurring species from the Nicotiana genus. Previous studies therefore focused on transgenic approaches to synthetize anatabine, most notably by generating transgenic lines with suppressed putrescine methyltransferase (PMT) activity. This led to promising results, but the global gene expression of plants with such distinct metabolism has not been analyzed. In the current study, we describe how these plants respond to topping and the downstream effects on alkaloid biosynthesis. Results: The surge in anatabine accumulation in PMT transgenic lines after topping treatment and its effects on gene expression changes were analyzed. The results revealed increases in expression of isoflavone reductase-like (A622) and berberine bridge-like enzymes (BBLs) oxidoreductase genes, previously shown to be crucial for the final steps of nicotine biosynthesis. We also observed significantly higher methylputrescine oxidase (MPO) expression in all plants subjected to topping treatment. In order to investigate if MPO suppression would have the same effects as that of PMT, we generated transgenic plants. These plants with suppressed MPO expression showed an almost complete drop in leaf nicotine content, whereas leaf anatabine was observed to increase by a factor of ~ 1.6X. Conclusion: Our results are the first concrete evidence that suppression of MPO leads to decreased nicotine in favor of anatabine in tobacco roots and that this anatabine is successfully transported to tobacco leaves. Alkaloid transport in plants remains to be investigated to higher detail due to high variation of its efficiency among Nicotiana species and varieties of tobacco. Our research adds important step to better understand pyrrolidine ring biosynthesis and its effects on gene expression and subsequent accumulation of anatabine. [ABSTRACT FROM AUTHOR]

Acute infectious urticaria, a subset of acute urticaria, with severe persistence wheals and systemic symptoms, response well to corticosteroids treatment in combination with antibiotics. The exact pathogenic mechanisms are not fully understood. In this study, we aim to analyze the different clinical features, compare the level of neutrophil activation, and investigate the expression of inflammatory related cytokine in patients with acute urticaria and acute infectious urticaria. Eighteen patients with acute infectious urticaria and eighteen patients with acute urticaria were included in this study. We analyzed the difference between the clinical features and the serum expressions of pro-inflammatory factors in the two groups, then examined the levels of inflammation-associated cytokines before and after treatment of acute infectious urticaria. Hematoxylin & eosin (HE) staining and immunohistochemistry (IHC) were used to further study the relationship between neutrophil and neutrophil-derived Myeloperoxidase (MPO) of lesions in the two groups. The expression levels of C-reactive protein (CRP), D-dimer, interleukin 6 (IL-6), IL-8 and chemokine ligand 8 (CCL8) in serum were significantly higher in acute infectious urticaria than acute urticaria. In acute infectious urticaria, the serum expression levels of CCL8 were significantly decreased after the treatment, a significant correlation observed between CRP levels and IL-6, both CCL8 and CRP were positively correlated with neutrophil granulocytes. Neutrophils infiltration were not observed by HE stains in two groups, but in IHC stains we found a positive expression of MPO in acute infectious urticaria lesions. Elevated neutrophil in the serum, which is associated with the levels of IL-8 & CCL8, and positively expressed MPO in lesions, may be involved in the pathogenic mechanism of acute infectious urticaria. [ABSTRACT FROM AUTHOR]

Cardiotoxicity is a major complication of anthracycline therapy that negatively impacts prognosis. Effective pharmacotherapies for prevention of anthracycline-induced cardiomyopathy (AICM) are currently lacking. Increased plasma levels of the neutrophil-derived enzyme myeloperoxidase (MPO) predict occurrence of AICM in humans. We hypothesized that MPO release causally contributes to AICM. Mice intravenously injected with the anthracycline doxorubicin (DOX) exhibited higher neutrophil counts and MPO levels in the circulation and cardiac tissue compared to saline (NaCl)-treated controls. Neutrophil-like HL-60 cells exhibited increased MPO release upon exposition to DOX. DOX induced extensive nitrosative stress in cardiac tissue alongside with increased carbonylation of sarcomeric proteins in wildtype but not in Mpo−/− mice. Accordingly, co-treatment of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with DOX and MPO aggravated loss of hiPSC-CM-contractility compared to DOX treatment alone. DOX-treated animals exhibited pronounced cardiac apoptosis and inflammation, which was attenuated in MPO-deficient animals. Finally, genetic MPO deficiency and pharmacological MPO inhibition protected mice from the development of AICM. The anticancer efficacy of DOX was unaffected by MPO deficiency. Herein we identify MPO as a critical mediator of AICM. We demonstrate that DOX induces cardiac neutrophil infiltration and release of MPO, which directly impairs cardiac contractility through promoting oxidation of sarcomeric proteins, cardiac inflammation and cardiomyocyte apoptosis. MPO thus emerges as a promising pharmacological target for prevention of AICM. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between serum myeloperoxidase (MPO) level and contrast-induced acute kidney injury (CI-AKI) and prognosis in patients undergoing emergency percutaneous coronary intervention (PCI) and its predictive value.Methods: 381 patients with acute myocardial infarction who underwent emergency PCI in The Second Affiliated Hospital of Anhui Medical University from March 2020 to February 2021 were selected. The clinical data were collected and the serum MPO level was detected within 12 hours before operation. According to the occurrence of CI-AKI after operation, they were divided into CI-AKI group (n=34)and non CI-AKI group (n=347). Multivariate Logistic regression was used to analyze the influencing factors of the incidence of CI-AKI in patients undergoing emergency PCI, and receiver operating characteristic (ROC) curve was used to evaluate the effectiveness of MPO in predicting CI-AKI. According to the best cutoff value, the patients were divided into high MPO group and low MPO group, and the patients were followed up for 12 months. The cumulative incidence of major adverse cardiovascular events (MACE) in high MPO group and low MPO group were analyzed by Kaplan-Meier survival curve. Results: The proportion of combined hypertension, diabetes mellitus, hyperlipidemia and smoking history proportion in CI-AKI group were higher than those in non CI-AKI group, and MPO level, creatinine level, contrast agent dosage were higher than those in non CI-AKI group (P＜0.05). Multivariate Logistic regression analysis showed that diabetes mellitus, high MPO and creatinine level were the risk factors influencing the occurrence of CI-AKI after emergency PCI (P＜0.05). ROC curve analysis showed that the area under the curve (AUC) of preoperative serum MPO level in predicting CI-AKI after emergency PCI was 0.726, and the optimal cut-off value was 491.12 μg/L, with a sensitivity of 58.80%, and specificity of 76.50%. A total of95 cases of MACE occurred one year after operation, with an incidence of 24.93%. Kaplan-Meier survival curve showed that the incidence of MACE in high MPO group was 27.37% higher than that in low MPO group 22.77% (P＜0.05). Conclusion: The serum MPO level of patients with CI-AKI after emergency PCI significantly increased, which is associated with the prognosis of patients, and it is a risk factor for CI-AKI, with high specificity, which can be an effective auxiliary indicator for predicting the occurrence of CI-AKI after emergency PCI. [ABSTRACT FROM AUTHOR]

Introduction. One of the leading causes in the mortality pattern of cancer patients is accounted for by thrombotic complications. Recent studies have shown that neutrophil extracellular traps (NETs) are involved in the activation of coagulation, contribute to the initiation and progression of thrombosis. In addition, NET-related effect on tumor progression and metastasis has been actively studied.Aim: to evaluate NET-related procoagulant activity in gynecological cancer patients.Materials and Methods. From April 2020 to October 2022, a prospective controlled interventional non-randomized study was conducted with 120 women. The main group included 87 patients aged 32 to 72 years with malignant neoplasms of the female genital organs and mammary glands who were hospitalized for elective surgical treatment or chemotherapy: uterine body cancer (subgroup 1; n = 18), ovarian cancer (subgroup 2; n = 26), cervical cancer – adenocarcinoma of the cervical canal (subgroup 3; n = 13), breast cancer (subgroup 4; n = 30). The control group consisted of 33 healthy women aged 32 to 68 years. In all women, plasma concentrations of citrullinated histone H3 (citH3), myeloperoxidase antigen (MPO:Ag), D-dimer, and thrombin–antithrombin (TAT) complexes were evaluated.Results. The magnitude of NETosis in cancer patients, assessed by level of citH3 (2.5 ± 0.7; 1.9 ± 0.8; 2.5 ± 0.7; 0.7 ± 0.5 ng/ml in four subgroups, respectively) and MPO:Ag (29.5 ± 13.1; 12.8 ± 3.7; 22.8 ± 8.7; 6.6 ± 2.5 ng/ml in four subgroups, respectively) was significantly higher compared to women in the control group (0.3 ± 0.1 ng/ml; p = 0.0001 and 2.5 ± 0.2 ng/ml; p = 0.0001). In parallel with increased NETosis markers in accordance with the disease stage, there was an increase in the concentration of hemostasis activation markers – D-dimer (1.7 ± 0.6; 2.0 ± 0.7; 1.4 ± 0.5; 1.5 ± 0.7 µg/ml in four subgroups, respectively) and TAT complexes (729.8 ± 43.9; 794.1 ± 164.8; 636.2 ± 149.5; 699.6 ± 165.7 pg/ml in four subgroups, respectively) exceeding their level in the control group (respectively, 0.4 ± 0.1 μg/ml; p = 0.0001 and 362.3 ± 0.1 pg/ml; p = 0.0001). The maximum values of parameters occurred at later stages according to the Classification of Malignant Tumours (tumor, nodus, metastasis, TNM). A significant correlation between TAT level and the concentrations of citH3 (r = 0.586; р = 0.04) and MPO:Ag was revealed (r = 0.631; р = 0.04).Conclusion. Tumor tissue creates milieu that stimulates NETs release, which, in turn, not only contribute to the creating a procoagulant state, but also might act as one of the factors that ensure tumor progression and metastasis. The development of targeted therapies acting on NETs has a potential to affect hemostasis in cancer patients and reduce rate of tumor growth and metastasis.

Background: Cigarette smoke (CS) is one of the primary causes of acute lung injury (ALI) via provoking pulmonary inflammation and oxidative stress. Despite substantial studies, no effective treatment for ALI is presently available. Purpose: New prospective treatment options for ALI are required. Thus, this project was designed to investigate the in vivo and in vitro protective effects of 70 % methanolic-aqueous crude extract of whole plant of Cichorium intybus (Ci.Mce) against CS-induced ALI. Study design: /methods: Initially, male Swiss albino mice were subjected to whole-body CS exposure for 10 continuous days to prepare CS-induced ALI models. Normal saline (10 mL/kg), Ci.Mce (100, 200, 300 mg/kg), and Dexamethasone (1 mg/kg) were orally administered to respective animal groups 1 h prior to CS-exposure. 24 hrs after the last CS-exposure, BALF and lungs were harvested to study the key characteristics of ALI. Next, HPLC analysis was done to explore the phytoconstituents. Results: Ci.Mce exhibited significant reductions in lung macrophage and neutrophil infiltration, lung weight coefficient, and albumin exudation. Additionally, it effectively ameliorated lung histopathological alterations and hypoxemia. Notably, Ci.Mce exerted inhibitory effects on the excessive generation of IL-6, IL-1β, and KC in both CS-induced ALI murine models and CSE-stimulated RAW 264.7 macrophages. Noteworthy benefits included the attenuation of oxidative stress induced by CS, evidenced by decreased levels of MDA, TOS, and MPO, alongside enhanced TAC production. Furthermore, Ci.Mce demonstrated a marked reduction in CS-induced NF-κB expression, both in vivo and in vitro. Conclusion: Consequently, Cichorium intybus could be a therapeutic option for CS-induced ALI due to its ability to suppress inflammatory reactions, mitigate oxidative stress, and quell NF-κB p65 activation.

Amyotrophic lateral sclerosis (ALS) is a chronic, progressive neurodegenerative disease characterized by the loss of motor neurons. Dysregulated peripheral immunity has been identified as a hallmark of ALS. Neutrophils, as the front-line responders of innate immunity, contribute to host defense through pathogen clearance. However, they can concurrently play a detrimental role in chronic inflammation. With the unveiling of novel functions of neutrophils in neurodegenerative diseases, it becomes essential to review our current understanding of neutrophils and to recognize the gap in our knowledge about their role in ALS. Thus, a detailed comprehension of the biological processes underlying neutrophil-induced pathogenesis in ALS may assist in identifying potential cell-based therapeutic strategies to delay disease progression. [ABSTRACT FROM AUTHOR]

Generalised pustular psoriasis (GPP) is a rare and severe neutrophilic skin disorder, manifesting with acute episodes of pustulation and systemic upset. The discovery of recessive IL36RN mutations associated with GPP has transformed our understanding of disease drivers, paving the way for the development of targeted anti‐IL36 therapeutics. In the light of these remarkable successes, this viewpoint reviews the significance of IL36RN mutations in GPP, their functional impact and their correlation with clinical phenotypes. It then covers the discovery of further genetic determinants (recessive MPO mutations) and risk factors (AP1S3 and CARD14 low‐frequency variants) for the disease. It discusses the growing evidence for genetic complexity in GPP and concludes by outlining collaborative strategies that may be adopted to overcome the challenges ahead. [ABSTRACT FROM AUTHOR]

Context. Melatonin influences female reproduction, but expression of the melatonin system has not been characterised in the ovine uterus. Aims. We aimed to determine whether synthesising enzymes (arylalkylamine N-acetyltransferase (AANAT) and N-acetylserotonin-O-methyltransferase (ASMT)), melatonin receptors 1 and 2 (MT1 and MT2), and catabolising enzymes (myeloperoxidase (MPO) and indoleamine 2,3-dioxygenase 1 and 2 (IDO1 and 2)), are expressed in the ovine uterus, and if they are influenced by the oestrous cycle (Experiment 1) or by undernutrition (Experiment 2). Methods. In Experiment 1, gene and protein expression was determined in sheep endometrium samples collected on days 0 (oestrus), 5, 10 and 14 of the oestrous cycle. In Experiment 2, we studied uterine samples from ewesfed either 1.5 or 0.5 times their maintenance requirements. Key results. We have demonstrated the expression of AANAT and ASMT in the endometrium of sheep. AANAT and ASMT transcripts, and AANAT protein were more elevated at day 10, then decreased to day 14. A similar pattern was observed for MT2, IDO1, and MPO mRNA, which suggests that the endometrial melatonin system might be influenced by ovarian steroid hormones. Undernutrition increased AANAT mRNA expression, but seemed to decrease its protein expression, and increased MT2 and IDO2 transcripts, whereas ASMT expression was unaffected. Conclusions. The melatonin system is expressed in the ovine uterus and is affected by oestrous cycle and undernutrition. Implications. The results help explain the adverse effects of undernutrition on reproduction in sheep, and the success of exogenous melatonin treatments in improving reproductive outcomes. [ABSTRACT FROM AUTHOR]

Trauma represents one of the leading causes of death worldwide. Traumatic injuries elicit a dynamic inflammatory response with systemic release of inflammatory cytokines. Disbalance of this response can lead to systemic inflammatory response syndrome or compensatory anti‐inflammatory response syndrome. As neutrophils play a major role in innate immune defence and are crucial in the injury‐induced immunological response, we aimed to investigate systemic neutrophil‐derived immunomodulators in trauma patients. Therefore, serum levels of neutrophil elastase (NE), myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) were quantified in patients with injury severity scores above 15. Additionally, leukocyte, platelet, fibrinogen and CRP levels were assessed. Lastly, we analysed the association of neutrophil‐derived factors with clinical severity scoring systems. Although the release of MPO, NE and CitH3 was not predictive of mortality, we found a remarkable increase in MPO and NE in trauma patients as compared with healthy controls. We also found significantly increased levels of MPO and NE on Days 1 and 5 after initial trauma in critically injured patients. Taken together, our data suggest a role for neutrophil activation in trauma. Targeting exacerbated neutrophil activation might represent a new therapeutic option for critically injured patients. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease characterized by the appearance of clearly demarcated erythematous and scaly plaques. It can be divided into various types, including plaque, nail, guttate, inverse, and pustular psoriasis. Plaque psoriasis is the most commonly occurring type, though there is another rare but severe pustular autoinflammatory skin disease called generalized pustular psoriasis (GPP), which manifests with acute episodes of pustulation and systemic symptoms. Though the etiopathogenesis of psoriasis is not yet fully understood, a growing body of literature has demonstrated that both genetic and environmental factors play a role. The discovery of genetic mutations associated with GPP has shed light on our comprehension of the mechanisms of the disease, promoting the development of targeted therapies. This review will summarize genetic determinants as known and provide an update on the current and potential treatments for GPP. The pathogenesis and clinical presentation of the disease are also included for a comprehensive discussion. [ABSTRACT FROM AUTHOR]

Abstract 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.

Abstract Background RLS-0071 is a novel 15 amino acid peptide dual-targeting anti-inflammatory inhibitor of complement and neutrophil effectors. RLS-0071 inhibits classical complement pathway activation at C1 and blocks the enzymatic activity of myeloperoxidase that leads to the generation of hypochlorous acid and induces NETosis. This peptide is being developed for the treatment of neonatal hypoxic ischemic encephalopathy (HIE) and neutrophilic pulmonary diseases. Methods This was a first in human clinical trial in healthy volunteers to assess safety and pharmacokinetics of single and multiple ascending doses of RLS-0071. Results RLS-0071 single and multiple doses were not associated with any clinically significant changes in safety parameters, laboratory test results or ECG measurements. Adverse events were similar between active drug and placebo groups. The pharmacokinetic profile demonstrated dose proportionality and two-compartment kinetics with rapid tissue distribution. Exploratory biomarker and target engagement assays demonstrated dose dependent classical complement pathway inhibition and myeloperoxidase binding. Discussion/Conclusion RLS-0071 was shown to be safe and well-tolerated at all doses tested with rapid tissue distribution and target engagement for both the classical complement pathway and myeloperoxidase. The findings are supportive of further clinical development and evaluation of RLS-0071 in conditions such as HIE and acute pulmonary diseases. Trial registration ClinicalTrials.gov Identifier: NCT05298787 March 28, 2022. Retrospectively registered.

Abstract Background The uncontrolled production of MPO promotes inflammation, oxidative stress and atherosclerosis. Serum MPO levels are increased in patients with diabetes compared with patients without diabetes. Objectives This study aimed to investigate whether the serum levels and activities of MPO are related to coronary plaque progression in patients with type 2 diabetes mellitus (T2DM). Material and methods Serum MPO levels and activities were measured in 161 patients with diabetes with plaque progression (plaque progression group) and 87 patients with diabetes with no plaque progression (no plaque progression group). These patients were eligible based on the inclusion criteria and received quantitative coronary angiography at baseline and after approximately 1 year of follow-up. The characteristics and parameters of the participants at baseline were documented. Results Serum MPO levels and activities were significantly higher in plaque progression group than in no plaque progression group (P

Abstract Background The significance of S100A8/A9 and S100A12 in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been clarified. This study was dedicated to exploring the potential pathogenic roles of S100A8/A9 and S100A12 in patients with myeloperoxidase (MPO)-ANCA-positive vasculitis. Methods Serum and urine concentrations of S100A8/A9 and S100A12 of forty-two AAV patients were evaluated. The influence of S100A8/A9 and S100A12 on the chemotaxis, the apoptosis, the release of IL-1β, the complement activation, the respiratory burst, as well as the neutrophil extracellular traps (NETs) formation of MPO-ANCA-activated neutrophils was investigated. Results The serum and urine S100A8/A9 and S100A12 of active MPO-AAV significantly increased (compared with inactive AAV and healthy controls, p

Objectives: The study aimed to evaluate the impact of aging on the formation of neutrophil extracellular traps (NETs). The impaired formation of NETs is the cause of an abnormal innate immune response. Material and Methods: The study included a total of 45 healthy male subjects of different age groups. Whole blood was collected from the subjects, and the concentration of myeloperoxidase (MPO), the main biocidal protein in NETs, was determined in serum using ELISA. The serum levels of circulating free DNA (cfDNA), which are the structural basis of NETs, were also measured by fluorescence. In addition, the white blood cell count was determined, whole blood smear was evaluated, and the neutrophillymphocyte ratio was calculated. The variations in the levels of NET biomarkers were analyzed in different age groups. Results: The low levels of MPO (243.70 ng/ml) and cfDNA (6.24 ng/100 µl) in boys indicated neutrophil insufficiency for NETosis in children. A progressive increase in the levels of MPO and cfDNA with age was observed among adolescents (420.91, p = 0.04; 13.55, p = 0.03, respectively), with the highest level noted in the healthy adult group (466.58, p = 0.01; 14.07, p = 0.01, respectively). The levels of the studied parameters were comparable in adolescents and young adults, which proved that the NETosis process was appropriate and suggested the attainment of neutrophil maturity for the release of NETs in adolescence. The levels of MPO and cfDNA were low in older men (225.46, p < 0.01; 5.19, p < 0.01, respectively) indicating impaired NET formation. Conclusions: Data on the generation of NETs in different age groups obtained in this study can allow a better understanding of the ontogenesis of the immune system in terms of the course of NETosis, and also indicate the need to support nonspecific responses in children and adults. Further research should be performed to determine the possibility of regulating the NETosis process. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare form of psoriasis, which is characterized by sudden onset of repeated erythema and pustule formation with generalized inflammation. Recent advances in molecular genetics have led to the identification of several genes associated with GPP, including IL36RN, CARD14, AP1S3, SERPINA3, and MPO. Of these, only limited cases of GPP have been reported to carry mutations in the AP1S3, SERPINA3, or MPO to date. In the present study, we investigated a Japanese patient with GPP and found a homozygous missense mutation c.1769G>T (p.Arg590Leu) in the MPO gene. Structural analysis predicted that the mutant MPO protein would abolish its ability to bind with heme protein. In vitro studies using cultured cells revealed that the mutant MPO was stably expressed, but completely lost its myeloperoxidase activity. Immunohistochemistry (IHC) using an anti‐MPO antibody showed markedly reduced expression of MPO protein in the patient's skin, suggesting that the mutation would lead to an instability of the MPO protein in vivo. Finally, IHC with an anti‐citrullinated Histone H3 antibody demonstrated a sparse formation of neutrophil extracellular traps within a Kogoj's spongiform pustule of the patient's skin. Collectively, we conclude that the c.1769G>T (p.Arg590Leu) in the MPO is a complete loss‐of‐function mutation associated with GPP in the patient. Our data further underscore critical roles of the MPO gene in the pathogenesis of GPP. [ABSTRACT FROM AUTHOR]

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Inflammation is the body's response to insults, for instance, lung inflammation is generally caused by pathogens or by exposure to pollutants, irritants and toxins. This process involves many inflammatory cells such as epithelial cells, monocytes, macrophages and neutrophils. These cells produce and release inflammatory mediators such as pro-inflammatory cytokines, lipids and reactive oxygen species (ROS). Lung epithelial cells and phagocytes (monocytes, macrophages and neutrophils) produce ROS mainly by the NADPH oxidase NOX1 and NOX2, respectively. The aim of this study was to investigate the effects of two NADPH oxidase inhibitors, apocynin and diphenyleneiodonium (DPI), on lipopolysaccharide (LPS)-induced lung inflammation in rats. Our results showed that apocynin and DPI attenuated the LPS-induced morphological and histological alterations of the lung, reduced edema and decreased lung permeability. The evaluation of oxidative stress markers in lung homogenates showed that apocynin and DPI inhibited LPS-induced NADPH oxidase activity, and restored superoxide dismutase (SOD) and catalase activity in the lung resulting in the reduction in LPS-induced protein and lipid oxidation. Additionally, apocynin and DPI decreased LPS-induced MPO activity in bronchoalveolar liquid and lung homogenates, TNF-α and IL-1β in rat plasma. NADPH oxidase inhibition could be a new therapeutic strategy for the treatment of inflammatory lung diseases. [ABSTRACT FROM AUTHOR]