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The global pandemic of obesity poses a serious health, social, and economic burden. Patients living with obesity are at an increased risk of developing noncommunicable diseases or to die prematurely. Obesity is a state of chronic low-grade inflammation. Neutrophils are first to be recruited to sites of inflammation, where they contribute to host defense via phagocytosis, degranulation, and extrusion of neutrophil extracellular traps (NETs). NETs are web-like DNA structures of nuclear or mitochondrial DNA associated with cytosolic antimicrobial proteins. The primary function of NETosis is preventing the dissemination of pathogens. However, neutrophils may occasionally misidentify host molecules as danger-associated molecular patterns, triggering NET formation. This can lead to further recruitment of neutrophils, resulting in propagation and a vicious cycle of persistent systemic inflammation. This scenario may occur when neutrophils infiltrate expanded obese adipose tissue. Thus, NETosis is implicated in the pathophysiology of autoimmune and metabolic disorders, including obesity. This review explores the role of NETosis in obesity and two obesity-associated conditions—hypertension and liver steatosis. With the rising prevalence of obesity driving research into its pathophysiology, particularly through diet-induced obesity models in rodents, we discuss insights gained from both human and animal studies. Additionally, we highlight the potential offered by rodent models and the opportunities presented by genetically modified mouse strains for advancing our understanding of obesity-related inflammation. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is a progressively developing arrhythmia. Electroanatomic remodeling may play an important role, both in the development of the disease and in the perpetuation and thus in the recurrence of AF. Objective: This study aimed to investigate potential biomarkers myeloperoxidase (MPO), N-terminal proatrial natriuretic peptide (NT-proANP), intercellular adhesion molecule-1, and matrix metalloproteinase-2 and their predictive value for AF recurrence in patients undergoing redo ablation. Methods: In this single-center prospective cohort study, 50 consecutive patients underwent ultra high-density mapping and redo ablation. Biomarkers were determined before ablation and at 6-month follow-up. Seven-day Holter was conducted to check for AF recurrence (>30 seconds). Results: Eleven (22%) patients showed AF recurrence after redo ablation. Receiver-operating characteristic curve analysis revealed venous MPO and NT-proANP (area under the curve [AUC] 0.755, 95% CI 0.599–0.912, P = .010; and AUC 0.752, 95% CI 0.551–0.953, P = .011) as acceptable predictors for intermediate AF recurrence, whereas matrix metalloproteinase-2, intercellular adhesion molecule-1, and established cardiovascular biomarkers such as N-terminal pro–B-type natriuretic peptide, troponin T, and C-reactive protein were not (all AUC

Leukaemia stem cells (LSCs) are major contributors to chemoresistance in acute myeloid leukaemia (AML). Identifying potential biomarkers within LSCs that can predict chemosensitivity in AML is key. This prospective study involved 20 consecutive de novo AML patients who underwent '7 + 3' induction therapy. The patients were divided into CR (n = 15) and non‐CR (n = 5) groups. Using single‐cell RNA sequencing, we examined the cellular states of bone marrow mononuclear cells from AML patients at diagnosis and identified LSC among these cells. Our results showed that in non‐CR AML patients, a significant increase in the proportion of immature cells during haematopoiesis within the AML cell populations was observed. Moreover, the expression of myeloperoxidase (MPO) (log2 fold‐change = 0.89; adjusted p < 0.0001) and thyrotropin‐releasing hormone (TRH) (log2 fold‐change = 0.65; adjusted p < 0.0001) was higher within LSCs in the CR group than in the non‐CR group. Furthermore, patients with higher expression of MPO and TRH demonstrated improved relapse‐free survival (p = 0.002 for MPO; p = 0.009 for TRH) and overall survival (p = 0.002 for MPO; p < 0.001 for TRH). The connection between MPO or TRH and chemosensitivity could be linked with the downregulation of transforming growth factor and the upregulation of interferon‐α. In conclusion, MPO and TRH in LSCs could serve as chemosensitivity biomarkers in AML. [ABSTRACT FROM AUTHOR]

Background: Chronic suppurative otitis media (CSOM) is a chronic and persistent inflammation of the middle part of the ear. CSOM is a multifactorial disease that involves interactions between the host, pathogen, genetics, and environment leading to oxidative stress conditions that cause prolonged inflammation. Many studies have been conducted to explain zinc's benefits in fighting oxidative stress. This study aimed to determine the effect of zinc supplementation on noncholesteatoma CSOM evaluated based on serum zinc and MPO levels and the presence of otorrhea. Materials and Methods: This study was an experimental research with pre and post-test control group design. This study was conducted in the ENT clinic of Dr. Moewardi Hospital, Indonesia, in July-September 2022. Subjects were divided into two different groups. The first group, or treatment group, was treated with 30 mg tablets/day zinc supplementation for 30 days. The second group, or the control group, was treated with a placebo of 30 mg/day for 30 days. Results: The result of this study showed that in the treatment group with zinc supplementation, the mean MPO level decreased significantly from 3.50 ng/mL to 0.73 ng/mL (p<0.001), the mean serum zinc level increased significantly from 119.53 μmol/L to 548.28 μmol/L (p<0.000), and 21 subjects recovered from otorrhea symptoms (p<0.000). Meanwhile, the mean MPO, zinc levels, and otorrhea symptoms did not show significant changes in the control group. Conclusions: Zinc supplementation can reduce serum MPO levels, increase serum zinc levels, and reduce otorrhea symptoms CSOM patients suffer. [ABSTRACT FROM AUTHOR]

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/Aim: Acute lung injury (ALI) is a syndrome characterized by the disruption of alveolar endothelial and epithelial barriers, neutrophilic infiltration in pulmonary regions, and non-cardiogenic edema, associated with high mortality and morbidity. Despite intensive research efforts, there is currently no approved specific treatment for the condition. The aim of this study was to investigate the potential beneficial effect of ischemic post-conditioning in lipopolysaccharide (LPS)- induced lung injury and its possible association with inflammatory and apoptotic processes. Materials and Methods: Lung injury was induced in rats by a single intraperitoneal administration of 10 mg/kg LPS. Under anesthesia, latex tourniquets were wrapped around both hind limbs of the animals in a region close to the body to achieve complete ischemia. The ischemic conditioning procedure consisted of four cycles of 10 min of ischemia followed by 10 min of reperfusion. Inflammation, and apoptosis levels were measured using ELISA. Hematoxylin and eosin staining was used for histopathological evaluation, while TUNEL staining was employed for apoptotic cell counting. One-way analysis of variance (ANOVA) with post hoc Tukey test was used for comparisons between groups. Results: Intraperitoneal LPS administration induced neutrophil infiltration and apoptotic cell death in lung tissue. These effects were prevented by remote ischemic postconditioning (RIPostC) application. Additionally, the beneficial effects of ischemic conditioning can be transferred via serum. Conclusion: RIPostC can ameliorate LPS-induced ALI. The mechanism of the protective effects of RIPostC may lie in the suppression of apoptosis and neutrophil infiltration. [ABSTRACT FROM AUTHOR]

Considering the beneficial effects of herbal medicine in comparison with synthetic drugs and also the recommendation of Iranian medical scholars on the use of Cassia fistula L. in gastrointestinal inflammations, in this study the effect of aqueous extract of C. fistula fruit on the histopathological improvement of ulcerative colitis was evaluated in rats. In this study, 30 rats with a weight range of 250-300 g and about 2 months were used. Ulcerative colitis was induced by acetic acid in rats, then the animals were treated orally with normal saline, sulfasalazine (360 mg/kg), or aqueous extract of C. fistula (600 and 800 mg/kg) once daily for 5 days. The animals were then sacrificed and their colons were evaluated macroscopically, histopathologically, and for myeloperoxidase (MPO) activity and weight. The severity and extent of colonic inflammation in animals receiving 400 and 800 mg/ml of C. fistula extract showed a significant decrease compared to those receiving normal saline (P< 0.05). A decrease in colon weight was observed in the group of animals receiving a concentration of 800 mg/ml of the extract. C. fistula aqueous extract did not show any effect in reducing the activity of the MPO enzyme. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Chronic wounds are a severe complication of diabetes. Dysregulated inflammatory signalling is thought to underly the poor healing outcomes. Yet, there is little information available on the acute response following injury and its impact on healing. Methods Using a murine full thickness excisional wound model, the current study therefore assessed the expression of pro‐inflammatory and pro‐resolving lipid mediators during the early stages post injury in acute and diabetic wounds and compared the timeframe for transitioning through the phases of healing. Tissue eicosanoid (LTB4, PGE2, TxA2, MaR1, RvE1, RvD1, PD) and MMP‐9 levels were assessed at 6 h post wounding using ELISAs. Wound closure, healing dynamics (histology), cellular infiltration and MPO, TNF‐α expression (IHC) were assessed at 6 h, day2, day7 post wounding. Results Eicosanoid expression did not differ between groups (LTB4 24–125 pg/mL, PGE2 63–177 pg/mL, TxA2 529–1184 pg/mL, MaR1 365–2052 pg/mL, RvE1 43–1157 pg/mL, RvD1 1.5–69 pg/mL, PD1 11.5–4.9 ng/mL). An inverse relationship (p

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases including granulomatous polyvasculitis (GPA), microscopic polyvasculitis (MPA), and eosinophilic granulomatous polyvasculitis (EGPA). The main antigens ANCA targets are protease 3 (PR3) and myeloperoxidase (MPO). PR3-ANCA is mainly related to GPA, while MPO-ANCA is related to MPA. The presence of these antibodies is critical to the diagnosis of AAV. Methods: A case of ANCA-associated vasculitis with PR3 and MPO antibody positive due to PTU was reported. Results: After the patients stopped PTU, PR3 antibody gradually decreased to negative, MPO antibody was relatively stable, and the fluorescent karyotype was p-ANCA. The positive PR3 antibody in this patient was considered to be related to PTU. Conclusion: ANCA, anti-PR3 antibody, and anti-MPO antibody are closely related to systemic vasculitis and are affected by many factors. Abnormal results in clinical work should be reviewed immediately and communicated with clinicians to avoid adverse consequences. [ABSTRACT FROM AUTHOR]

Background. Recurrent Pregnancy Loss (RPL) is a multifactorial disorder significantly impacting women’s health globally. Emerging research has implicated Neutrophil Extracellular Traps (NETs) in the pathophysiology of RPL, suggesting an immunological underpinning to miscarriage occurrences. Aim. The study aim to evaluate the role and expression of NETosis markers (MPO, histones H2A, H2B) in women with RPL in comparison to pregnant women. Methods. This prospective cohort study, conducted from January 2022 to July 2023, included 30 participants (20 RPL patients and 10 controls) from Al Basrah Maternity and Child Hospital. Immunohistochemical technique were employed to detect Myeloperoxidase and histones in placental samples. Statistical analysis was performed using SPSS, with significance set at p

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]

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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.

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.

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]

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.

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.

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.

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]

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

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]

• 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]