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We previously profiled the chemical composition of wax apple, Syzygium samarangense, leaf extract using HR-LC-MS/MS and reported its antioxidant, hepatoprotective and antitrypanosomal activities. The plant is widely used in traditional medicine to cure several ailments like bronchitis, asthma, diabetes, fever, pathogenic infections, gut spasms, as well as renal diseases. However, neither the gastroprotective effects nor the underlying mechanisms were explored. Here, we investigated the gastroprotective potential of the leaf extract on indomethacin-induced gastric ulcer in rats and explored the involved mechanism(s) of action. Administration of indomethacin significantly increased the ulcer index, mucosal injury, the gastric levels of the inflammatory markers nuclear factor kabba B-p65(NF-κB p65), myeloperoxidase (MPO), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), lipid peroxidation product, malondialdehyde (MDA) and Caspase-3 expression. It reduced the gastric levels of the endogenous antioxidants glutathione as well peroxidase (GPx), reduced glutathione (GSH) and the gastric mucosal protective factors, mucus secretion and goblet cells. Pretreatment with the leaf extract displayed a prominent decrease in the ulcer index, inflammatory cell infiltration, inflammatory markers, MDA, protein expression of Caspase-3 and a significant increase in the gastric levels of the endogenous antioxidants, mucus content and goblet cell proliferation when compared to the indomethacin group. The individual secondary metabolites of the extract exhibited low binding energy when docked into the prostaglandin receptors EP3 and EP4. This study revealed the gastroprotective effect of S. samarangense on indomethacin-induced gastric ulcer in rats. The gastroprotective effects might be attributed to cytoprotective, antioxidant, anti-inflammatory and antiapoptotic activities with a possible potential of activating EP3 and EP4 receptors. In conclusion, S. samarangense has a promising potential in the prevention of NSAIDs-induced ulcers.

Metropolitan Planning Organizations (MPOs) are required to measure emissions impacts of transportation plans and programs utilizing an emissions estimator such as MOtor Vehicle Emission Simulator (MOVES) or EMission FACtor (EMFAC) models demanding intensive data and time consumption to run models for scenario planning or sensitivity tests. Over time, transportation planning practitioners have developed and applied various sketch planning models in scenario planning and sensitivity tests. Still, many sketch planning models require extensive data collection/preparation and are overly complicated. This paper discusses an approach for a simple sketch planning method based on a Random Forest (RF) algorithm with a machine learning technique that practitioners may use to predict emissions with significantly short time and effort in data preparation and model execution. In this study, the algorithm is trained to simulate emissions estimates based on multi-year Constrained Long Range Plan (CLRP) data in the National Capital region for eight case studies. The study results showed that the proposed model predicted mobile source nitrogen oxides, volatile organic compounds and greenhouse gas emissions within +/- 10 percent of accuracy against MOVES counterparts with fewer resources in a shorter amount of time. The authors think that the model could be a sketch planning model evaluating emissions impacts of variables such as land use, trip purpose, network enhancement or mobility.

Pathogenesis of IMQ-induced psoriatic skin inflammation in mice and its interference by BD1 and UCB. IMQ is recognised by neutrophils through endosomal receptor-like TLR7/8 resulting in the activation of the MAPKs pathway leading to the induction of cytokines. Simultaneously, the activated MAPKs pathway releases MMP9 from stored gelatinase granules towards extracellular space. BD1 and UCB inhibit MMP9 expression, and activity. UCB and BD1 also inhibit the activation of the MAPK activation. [Display omitted] • Imiquimod induces MMP9 activity and MAPKs activation in vitro and in vivo. • UCB and BD1 ameliorate IMQ-induced psoriatic skin inflammation in mice. • UCB and BD1 inhibit IMQ-induced inflammatory cytokines and chemokines. • UCB and BD1 decreases IMQ-induced MMP9 activity and MAPKs activation. Psoriasis is a chronic immune-mediated inflammatory skin disease that involves dysregulated proliferation of keratinocytes. Psoriatic skin lesions are characterized by redness, thickness, and scaling. The interleukin axis of IL-23/IL-17 is critically involved in the development of human psoriasis. Imiquimod (IMQ), an agonist of TLR7 is known to induce psoriatic-like skin inflammation in mice. The topical application of IMQ induces systemic inflammation with increased proinflammatory cytokines in serum and secondary lymphoid organs. Further, matrix metalloproteases (MMPs) have been implicated in the pathophysiology of psoriatic-like skin inflammation. The increased MMP9 activity and gene expression of proinflammatory cytokines in IMQ-induced psoriatic skin is mediated by the activation of the MAPK pathway. Moreover, the increased expression of neutrophil-specific chemokines confirmed the infiltration of neutrophils at the site of psoriatic skin inflammation. In contrast, expression of IL-10, an anti-inflammatory cytokine gene expression is reduced in IMQ-treated mice skin. Topical application of unconjugated bilirubin (UCB) and its derivative dimethyl ester of bilirubin (BD1) on IMQ-induced psoriatic mice skin significantly mitigated the symptoms of psoriasis by inhibiting the activity of MMP9. Further, UCB and BD1 reduced neutrophil infiltration as evidenced by decreased myeloperoxidase (MPO) activity and reduced gene expression of proinflammatory cytokines, and neutrophil-specific chemokines. Apart from these modulations UCB and BD1 reduced MAPK phosphorylation and upregulated anti-inflammatory cytokines. To conclude, UCB and BD1 immunomodulated the psoriatic skin inflammation induced by IMQ in mice by inhibiting neutrophil mediated MMP9, decreased proinflammatory cytokines gene expression and modulating the MAPK pathway. [ABSTRACT FROM AUTHOR]

This study sought to explore the role of 7-ketocholesterol (7-KC) in liver damage caused by high cholesterol intake and its potential pathological mechanism in mice. Our in vivo findings indicated that mice fed a high-cholesterol diet had elevated serum levels of 7-KC, accompanied by liver injury and inflammation, similar to human nonalcoholic steatohepatitis. Furthermore, the high-cholesterol diet induced neutrophil infiltration, which played a critical role in liver damage through myeloperoxidase (MPO) activity. Upon stimulation with 7-KC, macrophages exhibited increased expression of C-X-C motif chemokine ligand 1 (CXCL1) and CXCL2, as well as ATP-binding cassette transporter A1 (ABCA1) and ABCG1. Hepatocytes, on the other hand, exhibited increased expression of CXCL2 and ABCG1. The infiltration of neutrophils in the liver was primarily caused by CXCL1 and CXCL2, resulting in hepatocyte cell death due to elevated MPO activity. Our data also revealed that the activation of macrophages by 7-KC via ABCA1 or ABCG1 was not associated with lipid accumulation. Collectively, these findings suggest that high cholesterol-induced hepatitis in mice involves, at least partially, the recruitment of neutrophils to the liver by 7-KC-activated macrophages. This is mediated by increased expression of CXCL1 and CXCL2 through ABCA1 or ABCG1, which act as 7-KC efflux transporters. Additionally, hepatocytes contribute to this process by increased expression of CXCL2 through ABCG1. Therefore, our findings suggest that 7-KC may play a role in high cholesterol-induced hepatitis in mice by activating macrophages and hepatocytes, ultimately leading to neutrophil infiltration. [ABSTRACT FROM AUTHOR]

It can be observed from aminoglycoside-induced hair cell damage that the cochlea basal turn is more susceptible to trauma than the apex. Drug-induced hearing loss is closely related to oxidative damage. The basilar membrane directly exposed to these ototoxic drugs exhibits differences in damage, indicating that there is an inherent difference in the sensitivity to oxidative damage from the apex to the base of the cochlea. It has been reported that the morphology and characteristics of the cochlea vary from the apex to the base. Therefore, we investigated oxidative stress-related gene expression profiles in the apical, middle, and basal turns of the cochlea. The Oxidative Stress RT2 Profiler™ PCR Array revealed that three of the 84 genes (Mb, Mpo, and Ncf1) were upregulated in the middle turn compared to their level in the apical turn. Moreover, eight genes (Mb, Duox1, Ncf1, Ngb, Fmo2, Gpx3, Mpo, and Gstk1) were upregulated in the basal turn compared to their level in the apical turn. The qPCR verification data were similar to that of the PCR Array. We found that MPO was expressed in the rat cochlea and protected against gentamicin-induced hair cell death. This study summarized the data for the gradient of expression of oxidative stress-related genes in the cochlea and found potential candidate targets for prevention of ototoxic deafness, which may provide new insights for cochlear pathology. • We assessed changes in gene expression levels in different cochlear turns • Three genes were found to be upregulated in the middle turn of the cochlea • Eight genes were found to be upregulated in the basal turn of the cochlea • We explained the expression pattern of MPO in rat cochlea • We found that inhibition of MPO protected hair cells damage induced by gentamicin [ABSTRACT FROM AUTHOR]

Our understanding of immune recognition and response to infection and non-infectious forms of cell damage and death is rapidly increasing. The major focus is on host immunity and microbiological invasion. However, it is also clear that these same pathways are important in the initiation and maintenance of autoimmunity and the damage caused to targeted organs. Understanding the involvement of cell death in autoimmune disease is likely to help define critical pathways in the immunopathogenesis of autoimmune disease and new therapeutic targets. An important immune responder cell population in host defense and autoimmunity is the neutrophil. One autoimmune disease where neutrophils play important roles is MPO-ANCA Microscopic Vasculitis. This a severe disease that results from inflammation to small blood vessels in the kidney, the glomeruli (high blood flow and pressure filters). One of the best studied ways in which neutrophils participate in this disease is by cell death through NETosis resulting in the discharge of proinflammatory enzymes and nuclear fragments. In host defense against infection this process helps neutralize pathogens however in auto immunity NETosis results in injury and death to the surrounding healthy tissues. The major autoimmune target in this disease is myeloperoxidase (MPO) which is found uniquely in the cytoplasm of neutrophils. Although the kidney is the major organ targeted in this disease MPO is not expressed in the kidney. Autoantibodies target surface MPO on activated circulating neutrophils resulting in their lodgment in glomerular capillaries where they NETose releasing extracellularly MPO and nuclear fragments initiating injury and planting the key autoantigen MPO. It is the cell death of neutrophils that changes the kidney from innocent bystander to major autoimmune target. Defining the immunopathogenesis of this autoimmune disease and recognizing critical injurious pathways will allow therapeutic intervention to block these pathways and attenuate autoimmune injury. The insights (regarding mechanisms of injury and potential therapeutic targets) are likely to be highly relevant to many other autoimmune diseases.

Enterotoxigenic Escherichia coli (ETEC) infection is a major cause of death in children under the age of five in developing countries. ETEC (O78:H11:CFA/I:LT+:ST+) mechanism has been studied in detail with either heat labile (LT) or heat stable (ST) toxins using in vitro and in vivo models. However, there is no adequate information on ETEC pathogenesis producing both the toxins (LT, ST) in BALB/c mice model. In this study, female mice have been employed to understand ETEC H10407 infection induced changes in physiology, biochemical and immunological patterns up to seven days post-infection and the antidiarrhoeal effect of Simarouba amara (Aubl.) bark aqueous extract (SAAE) has also been looked into. The results indicate that BALB/c is sensitive to ETEC infection resulting in altered jejunum and ileum histomorphology. Withal, ETEC influenced cAMP, PGE2, and NO production resulting in fluid accumulation with varied Na+, K+, Cl−, and Ca2+ levels. Meanwhile, ETEC subverted expression of IL-1β, intestine alkaline phosphatase (IAP), and myeloperoxidase (MPO) in jejunum and ileum. Our data also indicate the severity of pathogenesis reduction which might be due to attainment of equilibrium after reaching optimum rate of infection. Nevertheless, degree of pathogenesis was highly significant (p < 0.01) in all the studied parameters. Besides that, SAAE was successful in reducing the infectious diarrhoea by inhibiting ETEC H10407 in intestine (jejunum and ileum), and shedding in feces. SAAE decreased cAMP, PGE2, and fluid accumulation effectively and boosted the functional activity of immune system in jejunum and ileum IAP, MPO, IL-1β, and nitric oxide. [ABSTRACT FROM AUTHOR]

Our understanding of immune recognition and response to infection and non-infectious forms of cell damage and death is rapidly increasing. The major focus is on host immunity and microbiological invasion. However, it is also clear that these same pathways are important in the initiation and maintenance of autoimmunity and the damage caused to targeted organs. Understanding the involvement of cell death in autoimmune disease is likely to help define critical pathways in the immunopathogenesis of autoimmune disease and new therapeutic targets. An important immune responder cell population in host defense and autoimmunity is the neutrophil. One autoimmune disease where neutrophils play important roles is MPO-ANCA Microscopic Vasculitis. This a severe disease that results from inflammation to small blood vessels in the kidney, the glomeruli (high blood flow and pressure filters). One of the best studied ways in which neutrophils participate in this disease is by cell death through NETosis resulting in the discharge of proinflammatory enzymes and nuclear fragments. In host defense against infection this process helps neutralize pathogens however in auto immunity NETosis results in injury and death to the surrounding healthy tissues. The major autoimmune target in this disease is myeloperoxidase (MPO) which is found uniquely in the cytoplasm of neutrophils. Although the kidney is the major organ targeted in this disease MPO is not expressed in the kidney. Autoantibodies target surface MPO on activated circulating neutrophils resulting in their lodgment in glomerular capillaries where they NETose releasing extracellularly MPO and nuclear fragments initiating injury and planting the key autoantigen MPO. It is the cell death of neutrophils that changes the kidney from innocent bystander to major autoimmune target. Defining the immunopathogenesis of this autoimmune disease and recognizing critical injurious pathways will allow therapeutic intervention to block these pathways and attenuate autoimmune injury. The insights (regarding mechanisms of injury and potential therapeutic targets) are likely to be highly relevant to many other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Antioxidative peptides that inhibit myeloperoxidase (MPO) enzyme activity can effectively defend against oxidative stress damage. The antioxidant peptides from tuna protein were produced using alcalase hydrolysis and purified by ultrafiltration and Sephadex G-15, and the fractions with the highest free radicals scavenging ability and oxygen radical absorbance capacity (ORAC) values were sequenced using HPLC–MS/MS. Fifty-five peptide sequences were identified, 53 of which were successfully docked into MPO. The representative peptide ACGSDGK had better antioxidant activity and inhibition of MPO chlorination and peroxidation than the reference peptide hLF1-11. The docking model further showed intense molecular interactions between ACGSDGK and MPO, including hydrogen bonds, charge, and salt bridge interactions, which occluded the active site and blocked the catalytic activity of MPO. These results suggested that the antioxidant peptide ACGSDGK has the potential to inhibit oxidative stress and alleviate inflammation in vivo because of its inhibitory effect on the MPO enzyme.

Prostanoids and PGE2 in particular have been long viewed as one of the major mediators of inflammation in arthritis. However, experimental data indicate that PGE2 can serve both pro- and anti-inflammatory functions. We have previously shown (Kojima et al., J. Immunol. 180 (2008) 8361-8368) that microsomal prostaglandin E synthase-1 (mPGES-1) deletion, which regulates PGE2 production, resulted in the suppression of collagen-induced arthritis (CIA) in mice. This suppression was attributable, at least in part, to the impaired generation of type II collagen autoantibodies. In order to examine the function of mPGES-1 and PGE2 in a non-autoimmune form of arthritis, we used the collagen antibody-induced arthritis (CAIA) model in mice deficient in mPGES-1, thereby bypassing the engagement of the adaptive immune response in arthritis development. Here we report that mPGES-1 deletion significantly increased CAIA disease severity. The latter was associated with a significant (~3.6) upregulation of neutrophil, but not macrophage, recruitment to the inflamed joints. The lipidomic analysis of the arthritic mouse paws by quantitative liquid chromatography/tandem mass-spectrometry (LC/MS/MS) revealed a dramatic (~59-fold) reduction of PGE2 at the peak of arthritis. Altogether, this study highlights mPGES-1 and its product PGE2 as important negative regulators of neutrophil-mediated inflammation and suggests that specific mPGES-1 inhibitors may have differential effects on different types of inflammation. Furthermore, neutrophil-mediated diseases could be exacerbated by inhibition of mPGES-1.

Neutrophils are predominant immune cells that protect the human body against infections by deploying sophisticated antimicrobial strategies including phagocytosis of bacteria and neutrophil extracellular trap (NET) formation. Here, we provide an overview of the mechanisms by which neutrophils kill exogenous pathogens before we focus on one particular weapon in their arsenal: the generation of the oxidizing hypohalous acids HOCl, HOBr and HOSCN during the so-called oxidative burst by the enzyme myeloperoxidase. We look at the effects of these hypohalous acids on biological systems in general and proteins in particular and turn our attention to bacterial strategies to survive HOCl stress. HOCl is a strong inducer of protein aggregation, which bacteria can counteract by chaperone-like holdases that bind unfolding proteins without the need for energy in the form of ATP. These chaperones are activated by HOCl through thiol oxidation (Hsp33) or N-chlorination of basic amino acid side-chains (RidA and CnoX) and contribute to bacterial survival during HOCl stress. However, neutrophil-generated hypohalous acids also affect the host system. Recent studies have shown that plasma proteins act not only as sinks for HOCl, but get actively transformed into modulators of the cellular immune response through N-chlorination. N-chlorinated serum albumin can prevent aggregation of proteins, stimulate immune cells, and act as a pro-survival factor for immune cells in the presence of cytotoxic antigens. Finally, we take a look at the emerging role of HOCl as a potential signaling molecule, particularly its role in neutrophil extracellular trap formation. [ABSTRACT FROM AUTHOR]

Acute pancreatitis is a frequent life-threatening inflammatory disease of the pancreas characterized by severe abdominal pain that lasts for days to weeks. We sought to determine whether the antidiabetic and anti-inflammatory drug, metformin can substantially protect against acute pancreatitis in an animal model of L-arginine-induced acute pancreatitis, and whether this is associated with the augmentation of the anti-inflammatory cytokine interleukin-10 (IL-10) and inhibition of the enzyme that promotes tissue damage, myeloperoxidase (MPO). Rats were either injected with two doses of the amino acid L-arginine (2.5 gm/kg; i.p., at one-hour intervals) before being sacrificed after 48 hours (model group) or were pretreated with metformin (50 mg/kg) daily for two weeks prior to Larginine injections and continued receiving metformin until the end of the experiment (protective group). Using microscopic examination of the pancreas and blood chemistry, we observed that L-arginine induced acute pancreatic injury. This is demonstrated by an enlarged pancreas with patchy areas of haemorrhage, vacuolated cytoplasm and pyknotic nuclei in the acini, disorganized lobular architecture with infiltration of inflammatory cells within the interlobular connective tissue (CT) septa, and the presence of congested blood vessels that were substantially ameliorated by metformin. Metformin also significantly (p<0.05) inhibited L-arginine-induced MPO, lactate dehydrogenase (LDH), and the inflammatory biomarker tumor necrosis factor alpha (TNF-a). Whereas, metformin significantly (p<0.05) increased IL-10 levels that were inhibited by pancreatitis induction. We further demonstrated a significant (p<0.001) correlation between the scoring of the degree of pancreatic lobules damage tissue damage and the blood levels of TNF-a, IL-10, LDH, and MPO. Thus, metformin effectively protects against L-arginine-induced acute pancreatitis, which is associated with the inhibition of MPO and augmentation of IL-10. [ABSTRACT FROM AUTHOR]

Nephrologists are familiar with severe cases of anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) presenting as rapidly progressive glomerulonephritis. However, less is known about AAV with slowly progressive renal involvement. While its existence is acknowledged in textbooks, much remains unknown regarding its relative frequency versus more aggressive cases as well as about the optimal therapeutic approach and response to therapy. Moreover, this uncommon presentation may be underdiagnosed, given the scarce familiarity of physicians. In this issue of Clinical Kidney Journal , Trivioli et al. report the largest series to date and first systematic assessment of patients with AAV and slowly progressive renal involvement, defined as a reduction in estimated glomerular filtration rate (eGFR) of 25–50% in the 6 months prior to diagnosis after excluding secondary causes. Key findings are that slowly progressive AAV may be less common than previously thought, although it still represents the second most common presentation of renal AAV, it usually has a microscopic polyangiitis, anti-myeloperoxidase, mainly renal phenotype in elderly individuals, diagnosis may be late (over one-third of patients had end-stage kidney disease at diagnosis), clearly identifying an unmet need for physician awareness about this presentation, but those not needing renal replacement therapy at diagnosis still responded to immunosuppression. [ABSTRACT FROM AUTHOR]

The aim of the present study is to reveal the possible mechanism of anti-inflammatory activity of Crateva adansonii leaf extract to claim folkoric use of the plant in inflammation disease conditions. Isolation of chloroform leaf extract fraction (CEF) containing anti-inflammatory marker compound of the plant lupeol is done through column chromatography procedure, which is further confirmed by HPLC analysis with standard lupeol compound. The isolated marker compound lupeol from CEF shows significant in vitro anti-inflammatory effect compared to methanolic and chloroform leaf extracts (ME & CE) of the plant Crateva adansonii and reference standard indomethacin. Further in silico screening of lupeol and indomethacin against five crucial inflammatory molecular targets such as COX-2 (PDB ID: 4COX), MPO (PDB ID: 3ZS0), IL1β (PDBID: 1T4Q), IL6 (PDBID: 19PM) and TNFα (PDBID: 2AZ5) was done using autodock tool. Maximal binding affinity (− 11.6, − 9.0, − 9.9, − 7.5, − 9.0 kcal/mol) was exhibited by lupeol against all five targets of inflammation COX-2, MPO, TNFα, IL1β & IL6 respectively. In vitro and in silico modeling confirms the anti-inflammatory efficiency of lupeol and also unveils the hidden molecular mechanisms of folkoric use of Crateva adansonii plant in inflammatory disease conditions. [ABSTRACT FROM AUTHOR]

Sepsis is currently one of the leading causes of death in intensive care units (ICUs). Sesamin was previously reported to inhibit inflammation. However, no studies have revealed the impact of sesamin on sepsis. We studied the mechanism underlying the effect of sesamin on the pathophysiology of sepsis through the HMGB1/TLR4/IL-33 signalling pathway. Fifty male BALB/c mice (n = 10 per group) were used to establish a caecal ligation and puncture (CLP) mouse model, and given daily injections of sesamin at a low, middle, or high concentration (25, 50, or 100 μM) during the seven-day study period; survival curves were generated by the Kaplan–Meier method. H&E staining and TUNEL staining were performed to assess changes in intestinal morphology intestinal damage in the mouse intestinal epithelium. Molecules related to the HMGB1/TLR4/IL-33 pathway were assessed by RT-qPCR and Western blotting. We found mice in the sepsis group survived for only 4 days, while those treated with sesamin survived for 6–7 days. In addition, sesamin significantly relieved the increase in the levels of MPO (21%, 33.3%), MDA (40.5% and 31.6%), DAO (1.24-fold and 2.31-fold), and pro-inflammatory cytokines such as TNF-α (75% and 79%) and IL-6 (1-fold and 1.67-fold) 24 and 48 h after sepsis induction and downregulated the expression of HMGB1, TLR4, and IL-33 while upregulating the expression of ZO-1 and occludin. Sesamin improved the 7-day survival rate of septic mice, suppressed the inflammatory response in sepsis through the HMGB-1/TLR4/IL-33 signalling pathway, and further alleviated intestinal injury. [ABSTRACT FROM AUTHOR]

G-CSF for stem cell mobilization increases circulating levels of myeloid cells at different stages of maturation. Polymorphonuclear cells (PMNs) are also mobilized in high numbers. It was previously reported that G-CSF primes PMNs toward the release of neutrophils extracellular traps (NETs). Since NETs are often involved in thrombotic events, we hypothesized that high G-CSF blood concentrations could enhance PMN priming toward NET formation in healthy hematopoietic stem cell donors, predisposing them to thrombotic events. However, we found that G-CSF does not prime PMNs toward NETs formation, but increases the serum concentration of cell-free DNA, proteases like neutrophils elastase and myeloperoxidase, and reactive oxygen species. This could possibly create an environment disposed to induce thrombotic events in the presence of additional predisposing factors.

Babesiosis caused by the virulent tick-borne hemoprotozoan, Babesia rossi, results in a marked systemic inflammatory host response in dogs. Neutrophils form part of the innate immune response and contains myeloperoxidase (MPO) as the predominant component of the neutrophil lysosomal protein in azurophilic granules. The neutrophil myeloperoxidase index (MPXI), determined on the ADVIA hematology analyzer, is a quantitative estimate of intracellular MPO content. Objectives of this study were to: (a) compare MPXI in dogs with babesiosis with healthy control dogs; (b) compare MPXI in dogs that died from babesiosis with dogs that survived and controls; and (c) correlate the MPXI with the previously determined segmented and band neutrophil count and cytokine concentrations in dogs with babesiosis. Data for 140 dogs naturally infected with B. rossi and 20 healthy control dogs were retrospectively evaluated. Neutrophil counts and MPXI were determined on an ADVIA 2120 analyzer. Cytokine concentrations [interleukin (IL)-2, IL-6, IL-8, IL-10, IL-18, granulocyte-macrophage colony stimulating factor (GM-CSF), and monocyte chemo-attractant protein-1 (MCP-1)] were determined using a canine-specific multiplex immunoassay. The mortality rate of the Babesia-infected dogs was 11% (15/140). MPXI was significantly higher in Babesia-infected dogs (P = 0.033), and in Babesia-infected non-survivors (P = 0.011), compared with healthy control dogs. In Babesia-infected dogs a significant positive correlation was found between MPXI and IL-10 (r = 0.211, P = 0.039) and a significant negative correlation was found between MPXI and IL-8 (r = −0.350, P < 0.001). In Babesia-infected non-survivors, significant positive correlations were found between MPXI and IL-2 (r = 0.616, P = 0.033), IL-6 (r = 0.615, P = 0.033), IL-18 (r = 0.613, P = 0.034), GM-CSF (r = 0.630, P = 0.028), and MCP-1 (r = 0.713, P = 0.009). In Babesia-infected survivors, a significant negative correlation was found between MPXI and IL-8 (r = −0.363, P = 0.001). MPXI was correlated with pro-inflammatory cytokines in Babesia-infected dogs that died. The potential of MPXI as a novel marker of inflammation and prognosis in dogs infected with B. rossi, thus warrants further investigation.

SARS-CoV-2, the virus that causes COVID-19, has given rise to one of the largest pandemics, affecting millions worldwide. High neutrophil-to-lymphocyte ratios have been identified as an important correlate to poor recovery rates in severe COVID-19 patients. However, the mechanisms underlying this clinical outcome and the reasons for its correlation to poor prognosis are unclear. Furthermore, the mechanisms involved in healthy neutrophils acquiring a SARS-CoV-2-mediated detrimental role are yet to be fully understood. In this study, we isolated circulating neutrophils from healthy donors for treatment with supernates from infected epithelial cells and direct infection with SARS-CoV-2 in vitro. Infected epithelial cells induced a dysregulated degranulation of primary granules with a decrease in myeloperoxidase (MPO), but slight increase in neutrophil elastase release. Infection of neutrophils resulted in an impairment of both MPO and elastase release, even though CD16 receptor shedding was upregulated. Importantly, SARS-CoV-2-infected neutrophils had a direct effect on peripheral blood lymphocyte counts, with decreasing numbers of CD19+ B cells, CD8+ T cells, and CD4+ T cells. Together, this study highlights the independent role of neutrophils in contributing to the aberrant immune responses observed during SARS-CoV-2 infection that may be further dysregulated in the presence of other immune cells.

Background: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in young infants. However, it is also a significant pathogen in older adults. Validated biomarkers of RSV disease severity would benefit diagnostics, treatment decisions, and prophylactic interventions. This review summarizes knowledge of biomarkers for RSV disease in adults.Methods: A literature review was performed using Ovid Medline, Embase, Global health, Scopus, and Web of Science for articles published 1946-October 2016. Nine articles were identified plus 9 from other sources.Results: From observational studies of natural infection and challenge studies in volunteers, biomarkers of RSV susceptibility or disease severity in adults were: (1) lower anti-RSV neutralizing antibodies, where neutralizing antibody (and local IgA) may be a correlate of susceptibility/severity; (2) RSV-specific CD8+ T cells in bronchoalveolar lavage fluid preinfection (subjects with higher levels had less severe illness); and (3) elevated interleukin-6 (IL-6), IL-8, and myeloperoxidase levels in the airway are indicative of severe infection.Conclusions: Factors determining susceptibility to and severity of RSV disease in adults have not been well defined. Respiratory mucosal antibodies and CD8+ T cells appear to contribute to preventing infection and modulation of disease severity. Studies of RSV pathogenesis in at-risk populations are needed. [ABSTRACT FROM AUTHOR]

In the article, the authors discuss a study which examined the prevalence of myeloperoxidase (MPO) deficiency in patients using the ADVIA 2120i haematology analyser. Also cited are the peroxidase activity and nuclear density analysis (PANDA) cytochemical methods used in the analyser, as well as the differentiation of basophils, mononuclear, and polymorphonuclear leucocytes.

The identification of disease alleles underlying human autoinflammatory diseases can provide important insights into the mechanisms that maintain neutrophil homeostasis. Here, we focused our attention on generalized pustular psoriasis (GPP), a potentially life-threatening disorder presenting with cutaneous and systemic neutrophilia. Following the whole-exome sequencing of 19 unrelated affected individuals, we identified a subject harboring a homozygous splice-site mutation (c.2031−2A>C) in MPO. This encodes myeloperoxidase, an essential component of neutrophil azurophil granules. MPO screening in conditions phenotypically related to GPP uncovered further disease alleles in one subject with acral pustular psoriasis (c.2031−2A>C;c.2031−2A>C) and in two individuals with acute generalized exanthematous pustulosis (c.1705C>T;c.2031−2A>C and c.1552_1565del;c.1552_1565del). A subsequent analysis of UK Biobank data demonstrated that the c.2031−2A>C and c.1705C>T (p.Arg569Trp) disease alleles were also associated with increased neutrophil abundance in the general population (p = 5.1 × 10−6 and p = 3.6 × 10−5, respectively). The same applied to three further deleterious variants that had been genotyped in the cohort, with two alleles (c.995C>T [p.Ala332Val] and c.752T>C [p.Met251Thr]) yielding p values < 10−10. Finally, treatment of healthy neutrophils with an MPO inhibitor (4-Aminobenzoic acid hydrazide) increased cell viability and delayed apoptosis, highlighting a mechanism whereby MPO mutations affect granulocyte numbers. These findings identify MPO as a genetic determinant of pustular skin disease and neutrophil abundance. Given the recent interest in the development of MPO antagonists for the treatment of neurodegenerative disease, our results also suggest that the pro-inflammatory effects of these agents should be closely monitored. [ABSTRACT FROM AUTHOR]

Quantitative structure-activity relationships and drug-likeness evaluations were investigated for 33 compounds of 1,2-diazole derivatives as anti-mycobacterium tuberculosis. MLR procedures were used to obtain QSAR models. The predictivity of the models was estimated using cross-validation with the leave-one-out method. The results show a high correlation between the experimental and predicted activity values, indicating the good quality of the QSAR model. [ABSTRACT FROM AUTHOR]

Objective: Inflammatory bowel disease (IBD) is an idiopathic disease associated with changes in the immune system and in the intestinal microbiota. The most accepted hypothesis of IBD pathogenesis is thought to be the abnormal immunological response and chronic intestinal inflammation, which is caused by the complex interactions between genetic, environmental factors and the host immune system. Microbial flora is important in the maturation of the immune system. Dysbiosis is defined as changes in intestinal microbiota composition and function. Clinical and experimental studies support that dysbiosis plays a significant role in the etiopathogenesis of IBD. Probiotics are useful live microorganisms that provide the intestinal balance in the host. In this study, we aimed to evaluate the anti-inflammatory and anti-oxidant activities of Enterococcus faecium, Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Bifidobacterium longum bacteria in the experimental colitis model. Methods: Twenty-four female Wistar-Albino rats and 30 mg 0.5 mL trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol which induced colitis by intrarectal installation. Rats were divided into four groups; healthy control (sham: group A), TNBS colitis (group B), (TNBS + methylprednisolone: group C) and probiotic (TNBS + P: group D). The rats were sacrificed on the 8th day. Macroscopic and microscopic scores, tissue myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured. Results: Macroscopic and microscopic scores levels in group A were significantly lower than in group B, C and D. Macroscopic and microscopic scores levels in group C were significantly lower than in group B. Macroscopic scores were statistically similar between group C and D. There was a statistically significant difference between the groups in terms of median MDA levels and median SOD levels (p<0.001). There was no statistically significant difference between the groups in terms of median MPO levels (p=0.114). Median MPO levels were 0.27 (0.15-0.30) in group A, 0.44 (0.22-0.61) in group B, 0.28 (0.25-0.50) in group C, and 0.30 (0.25-0.37) in group D (p=0.114). Median MDA levels were 1.1 (1.0-2.8) in group A, 4.3 (3.1-5.5) in group B, 3.8 (3.2-4.2) in group C, and 3.9 (3.1-4.2) in group D (p<0.001). Median SOD levels were 160.7 (150.1-161.7) in group A, 141.6 (137.9-147.3) in group B, 157.6 (155.2-167.7) in group C, and 164.7 (160.3-168.3) in group D (p<0.001). MDA levels were statistically significantly different between each group. These levels were significantly higher in group B, C and D than in group A; statistically similar in group C and D; and statistically higher in group B than in group C and D (p<0.001 & p=0.047). SOD levels were statistically significantly different between each group. They were significantly lower in group B, C and D than in group B; statistically significantly different in group A, C and D; and statistically higher in group D than in group A and C. Conclusion: Our study showed that probiotics regulate the balance between anti-oxidant and oxidant systems. Therefore, probiotics can be used as a supportive treatment in inflammatory bowel diseases if promoted by clinical trials. [ABSTRACT FROM AUTHOR]

Objective: Inflammatory bowel disease (IBD) is an idiopathic disease associated with changes in the immune system and in the intestinal microbiota. The most accepted hypothesis of IBD pathogenesis is thought to be the abnormal immunological response and chronic intestinal inflammation, which is caused by the complex interactions between genetic, environmental factors and the host immune system. Microbial flora is important in the maturation of the immune system. Dysbiosis is defined as changes in intestinal microbiota composition and function. Clinical and experimental studies support that dysbiosis plays a significant role in the etiopathogenesis of IBD. Probiotics are useful live microorganisms that provide the intestinal balance in the host. Aim: In this study, we aimed to evaluate the anti-inflammatory and antioxidant activities of Enterococcus faecium, Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Bifidobacterium longum bacteria in the experimental colitis model. Methods: Twenty-four female Wistar-Albino rats and 30 mg 0.5 ml trinitrobenzenesulphonic acid (TNBS) dissolved in 50% ethanol which induces colitis by intrarectal installation. Rats divided into four groups; healty control (Sham: Group A), TNBS colitis (Group B), metilprednisolone (TNBS+MP: Group C) and probiotic (TNBS+P:Group D). The rats were sacrificed on 8th day. Macroscopic and microscopic scores, tissue myeloperoxidase (MPO), Malondialdehit (MDA) and superoxide dismutase (SOD) levels were measured. Results: Macroscopic and microscopic scores levels in Group A were significantly lower than Group B, C and D. Macroscopic and microscopic scores levels in Group C were significantly lower than Group B. Macroscopic scores were statistically similar between Group C and D. There was a statistically significant difference between the groups in terms of median MDA levels and median SOD levels (p<0,001). There was no statistically significant difference between groups in terms of median MPO levels (p = 0,114). Median MPO levels were in Group A: 0,27 (0,15-0,30), Group B: 0,44 (0,22-0,61), Group C: 0,28 (0,25-0,50), Group D: 0,30 (0,25-0,37) (p=0,114). Median MDA levels were in Group A: 1,1 (1,0-2,8), Group B: 4,3 (3,1-5,5), Group C: 3,8 (3,2-4,2), Group D: 3,9 (3,1-4,2) (p<0,001). Median SOD levels were in Group A:160,7 (150,1-161,7), Group B: 141,6 (137,9-147,3), Group C: 157,6 (155,2-167,7), Group D:164,7 (160,3-168,3) (p<0,001).MDA levels were statistically significant difference between each group. These levels in Group B,C and D were significantly higher than Group A; in Group C and D were statistically similar; in Group B were statistically higher than Group C and D (p<0.001 & p=0,047). SOD levels were statistically significant difference between each group Group B,C and D were significantly lower than Group B; in Group A,C and D were statistically significant difference; in Group D were statistically higher than Group A and C. Conlusion: Our study showed that probiotics regulate the balance between antioxidant and oxidant systems. Therefore, probiotics can be used as supportive treatment in inflammatory bowel diseases if promoted by clinical trials. [ABSTRACT FROM AUTHOR]

Osteogenic differentiation, proliferation, and/or apoptosis of bone marrow mesenchymal stem cells (BMSCs) are involved in the progression of postmenopausal osteoporosis (PMO). However, circular RNA (circRNA)-mediated changes in the cellular function of BMSCs in PMO are still unclear. This study revealed the excellent ability of circ-Plod2 to promote osteogenic differentiation of BMSCs and its molecular mechanisms. In this study, ovariectomized (OVX) rats and control (Sham) rats were used to simulate PMO. Initially, we found that the expression of circ-Plod2 in OVX BMSCs is down-regulated and the expression of the Mpo gene is up-regulated by sequencing and verification. Further, we confirmed that circ-Plod2 is located in the cytoplasm and belongs to exon-type circRNA. Interestingly, circ-Plod2 promotes Mpo-dependent osteogenic differentiation of BMSCs without affecting proliferation, apoptosis, adipogenic differentiation, or chondrogenic differentiation of BMSCs. Mechanistically, we demonstrated that circ-Plod2 specifically binds IGF2BP2 to form an RNA-protein complex that destabilizes Mpo mRNA. Overexpression of circ-Plod2 in the bone marrow cavity effectively alleviated osteoporosis in OVX rats and inhibited the expression of MPO in BMSCs. Together, this study reveals that circ-Plod2 destabilizes Mpo mRNA by binding to IGF2BP2 to promote osteogenic differentiation of BMSCs to alleviate osteoporosis. The findings of this study may provide biomarkers for the diagnosis of PMO, and may also provide potential strategies for the clinical treatment of PMO. In postmenopausal osteoporotic rats, the Plod2 gene overproduces circ-Plod2. Circ-Plod2 translocated from the nucleus to the cytoplasm forms a complex with the RNA-interacting protein IGFBP2. Further, the complex destabilizes Mpo gene mRNA to inhibit the expression of Mpo. Macroscopically, the decreased expression of Mpo further inhibits the osteogenic differentiation of BMSCs and leads to the occurrence of postmenopausal osteoporosis. [Display omitted] [ABSTRACT FROM AUTHOR]

A relationship is emerging between SARS-CoV-2 infections and ANCA-associated vasculitis (AAV) because: (i) the pulmonary involvement of COVID-19 may mimic that observed in patients with AAV; (ii) the two diseases may occur together; (iii) COVID-19 may trigger AAV. However, few cases of AAV have been identified so far in COVID-19 patients. To define the frequency of ANCA autoimmunity in patients with SARS-CoV-2 infection, we analyzed the serum ANCAs and the serum PR3 and MPO antigens by immunoassays in 124 adult patients with a diagnosis of SARS-CoV-2 infection (16 were asymptomatic and 108 were hospitalized) and 48 control subjects. The serum ANCAs were significantly higher in the hospitalized patients compared with either the controls or the asymptomatic patients and increased with the progression of the COVID-19 severity. After one week of hospitalization, the values were significantly lower. In contrast, no differences emerged among the controls, asymptomatic and hospitalized patients for the PR3 and MPO serum levels. None of the patients had clinical signs of AAV with the exception of a severe pulmonary involvement. Further studies are necessary to define whether the increase in the serum ANCAs might mask subclinical vasculitis in a percentage of patients with SARS-CoV-2 infection or it is an epiphenomenon of SARS-CoV-2 infection with no clinical manifestations.

Oxidative stress and inflammation are implicated in obesity. Therefore, we investigated whether moderate and short-term calorie restriction (CR) reflects a real-life situation, mediates weight loss, and improves oxidative stress markers. We analyzed oxidative stress markers in patients with obesity undergoing moderate CR. Serum oxidative stress markers (myeloperoxidase (MPO), superoxide dismutase (SOD), catalase, total antioxidant status (TAS), and reactive oxygen species (ROS) (generation by endothelial cells in vitro)) were measured in 53 subjects (mean BMI 37.8 ± 5.9 kg/m2) who underwent 8 weeks of CR, which included a reduction of 300–500 kcal/day. MPO was the most CR-sensitive parameter. The mean level of serum MPO in patients with obesity was 20% higher than that in post CR intervention (p < 0.001). SOD increased by 12% after CR (p < 0.05), which was largely due to the improvement in glucose tolerance and the reduction in insulin resistance after CR. Other tested parameters were not modified during the treatment. CR resulted in an expected decrease in body weight (by 5.9 ± 4.6 kg, p < 0.0001) and other anthropometric parameters. Additionally, it was accompanied by a significant change in hsCRP, hsTNF alpha, hsIL-6, leptin (all p < 0.0001), and HOMA-IR (p < 0.05). Cardiovascular and metabolic parameters were also partially improved. Short-term, moderate CR partially improves antioxidant capacity but is enough to substantially change anthropometric parameters in obese patients. Our observations indicate that mimicking real-life situations and low-cost dietary intervention can be successfully implemented in obesity treatment with a simultaneous moderate effect on antioxidant status.

This study evaluated the mitigating effects of dietary chlorogenic acid (CGA) on colon damage and the bacterial profile in a mouse model of dextran sulfate sodium (DSS)-induced colitis. C57BL/6J mice were randomly assigned to receive one of the following treatments: (i) basal diet; (ii) basal diet with 2% CGA; (iii) basal diet with 2.5% DSS or (iv) basal diet with 2% CGA and 2.5% DSS. Following a 2-week pre-treatment period, mice in the DSS and CGA-DSS groups received 2.5% DSS in drinking water for 5 days, while the other two groups received sterile water. Compared to DSS alone, CGA was found to reduce the disease activity index, myeloperoxidase activity and tumor necrosis factor-α levels in colon tissues (P < 0.05). CGA also ameliorated DSS-induced inflammatory responses, reduced colon shortening and decreased the histological scores (P < 0.05). In an evaluation of the relative abundances of bacteria in the fecal microbiota, we found that CGA reversed the decrease in diversity caused by DSS and improved the relative abundance of organisms in the genus Lactobacillus (P < 0.05). These results indicate that CGA maintains intestinal health and reduces DSS-induced colon injury by decreasing the production of pro-inflammatory cytokines and restoring intestinal microbial diversity.

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Objective: To study the prevalence of chronic fatigue syndrome (CFS) and association of CFS with other clinical and neuropsychological manifestations of Parkinson's disease (PD) as well as with serum inflammatory markers and genetic polymorphisms., Material and Methods: The study included 533 patients with PD. All patients underwent clinical, neurological examination and neuropsychological testing using validated questionnaires: MoCA test, HADS, BDI-II, the Fatigue Severity Scale (FSS). Serum concentrations of inflammatory markers (slCAM-1, sVCAM-1, NCAM, CCL5, PAI-1 and MPO) were assessed in 144 patients using xMAP technology. A case-control study of CCL5 (rs2107538) and PAI-1 (rs2227631) gene polymorphisms was performed in connection with PD development and in groups differing in the presence/absence of CFS in PD. In addition, the relationship of these polymorphisms with variability in the levels of the corresponding proteins in the blood serum of patients was studied. Genotyping of CCL5 (rs2107538) and PAI-1 (rs2227631) polymorphisms was performed using real-time PCR with TaqMan probes., Results: CFS is common in 66.7% of patients in the PD group. In addition, non-motor symptoms (emotional-affective, cognitive, autonomic disorders and pain) were more common in patients with CFS. A strong correlation has been established between the severity of CFS assessed with FSS and serum concentrations of CCL5, sVCAM-1, NCAM and slCAM-1. In newly diagnosed patients with PD who were not taking antiparkinsonian drugs at the time of the study and had CFS, higher correlations were noted between inflammatory markers and the severity of CFS manifestations. When comparing the distribution of genotypes and alleles of CCL5 (rs2107538) and PAI-1 (rs2227631) polymorphisms, some differences were found between the groups of patients with PD and controls ( p <0.05). However, these polymorphisms did not affect the variability of serum protein levels CCL5 and PAI-1, respectively, nor did they affect the development of CFS in patients with PD., Conclusion: CFS is common in PD, and patients with PD and CFS are characterized by elevated levels of serum markers CCL5, sVCAM-1, slCAM-1 and NCAM, suggesting the importance of the inflammatory component in the development of neurodegenerative disease. In addition, the clinical course of PD in patients with CFS is aggravated by other non-motor manifestations, including emotional-affective, cognitive, autonomic disorders and pain. These results highlight the potential contribution of an inflammatory component to the development of fatigue associated with PD, starting from the earliest clinical stages of the disease.

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.

Background: Several 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., Methods: Instrumental 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., Results: The 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)., Conclusion: Our 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tang, Li, Huang and Liu.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction Pregnancy is characterized by increased innate immune response, with low-grade systemic inflammation. The specific role of MPO during normal pregnancy remains not well understood. Therefore, the aim of this study was to evaluate plasma levels of MPO, hs-CRP, total leukocyte, absolute neutrophil and monocyte counts, in all trimesters of normal human pregnancy compared with non-pregnant controls. In addition, possible fluctuations of MPO according to different inflammatory conditions in the normal gestation were studied. Materials and methods Case-control study (n=84) developed with 63 normal pregnant women and 21 healthy non-pregnant women. Total leukocyte, absolute neutrophils and absolute monocytes count, hs-CRP and MPO were measured in non-pregnant women and normal human pregnancy. They were evaluated according to the 3 trimesters of pregnancy and systemic low grade inflammatory status, which was identified through increased hs-CRP levels. Results MPO levels in the normal pregnant women were not elevated in every 3 trimesters of pregnancy (P=0.456) or in systemic inflammation (P=0.446). The hs-CRP levels, total leukocyte, absolute neutrophil and monocyte counts are present in higher concentrations in normal pregnant women in relation to non-pregnant women. Conclusions The MPO did not show fluctuations in plasma levels during the 3 trimesters of gestation or in relation to different inflammation conditions. Considering MPO and hs-CRP levels are changed in high cardiovascular risk conditions and MPO levels (unlike hs-CRP) didn't increase during non complicated pregnancy, MPO could be a better biomarker than hs-CRP to monitor these patients. [ABSTRACT FROM AUTHOR]

Background/purpose: A reliable noninvasive prognostic factor of ANCA-associated vasculitis (AAV) is still lacking, but little research has focused on the value of MPO-ANCA titers in patients with active vasculitis. This study explored the prognostic significance of MPO-ANCA titer in active AAV patients.Methods: Ninety-seven inpatients diagnosed with MPO-ANCA associated vasculitis at Linkou Chang Gung Memorial hospital and Keelung Chang Gung Memorial hospital from January 2005 to December 2016 were enrolled. Serum ANCA titers and basic characteristics of these patients at diagnosis were collected completely Medical records since AAV diagnosis were reviewed to evaluate two years renal and patient outcome.Results: The patients were divided into the two groups according to the median ANCA titers, the more than four times of the normal cut-off value group (high titer group) and the less ANCA titer group (low titer group). The high titer group had significant poor initial renal function (eGFR 16.7 vs 40.7 mL/min/1.73 m2, P = 0.006), and significantly lower two-year renal survival (Log rank P < 0.001). Whereas patient survival (Log rank P = 0.894) was not different The Cox regression models revealed that baseline Birmingham Vasculitis Activity Score, eGFR and a 4-fold increase in ANCA titer were associated with the requirement of permanent dialysis. In the subgroup analysis, the ANCA titer was still an important risk factor for renal outcomes (P = 0.036) in patients with better initial renal function (eGFR≧15 mL/min).Conclusion: This study demonstrated that higher MPO-ANCA titers at diagnosis was associated with poor initial renal function and 2-year renal outcomes. [ABSTRACT FROM AUTHOR]

Bacground: Myeloperoxidase (MPO) is a strong oxidant and toxic to microorganisms with excess production causing tissue damage. We aimed to determine the effect of N-acetylcysteine (NAC) 600 mg orally 3 times a day for 3 consecutive days on MPO levels and left ventricle myocardial performance index (LVMPI/Tei index) in ST elevation myocardial infarction (STEMI) patients treated with fibrinolytics. Methods: Pre- and post-design, single blind experimental randomized trial, conducted on 32 patients with STEMI at Intensive Cardiovascular Care Unit (ICVCU). The subjects were divided into 2 groups: 17 patients received 600 mg t.i.d NAC for 72 hours and 15 controls. MPO levels before and after 72 hours and Tei index 72 hours after NAC therapy were measured. Statistical analysis of MPO level and Tei index were analyzed with SPSS 22. Tei index was measured using the pulsed wave Doppler (PWD) and tissue Doppler imaging (TDI). Results: NAC administration showed decrease in the marker of MPO (112.76±57.28 vs 180.40±69.03, p=0.001) and delta MPO (- 50.15±46.62 vs 12.06±108.65) 72 hours after NAC therapy compared with control. NAC improved the LVMPI value compared to the control group. Tei index examination using PWD (0.39±0.11 vs 0.49±0.08, p=0.005) and that using TDI (0.41±0.08 vs 0.57±0.08, p=0.001) showed improved values for NAC administration than those with controls. Conclusion: NAC 600 mg orally 3 times a day for 3 consecutive days can reduce MPO levels and improve diastolic function by decreasing LVMPI values. [ABSTRACT FROM AUTHOR]

Cysteine is important for protein synthesis, detoxification, and diverse metabolic functions. However, cysteine metabolism has been poorly described in fish, and the role of the therapeutic effect in pesticide toxicology on aquatic organisms is unknown. The aim of this study was to determine the effects of regular cysteine treatment on the hematology, biochemistry, apoptosis, oxidative DNA damage, and antioxidant parameters in fish blood after chemical application. Therefore, fish were exposed to cypermethrin for 2 weeks. Then two different concentrations of N-acetylcysteine (NAC) were applied for a 4-day treatment period and compared with the group of the self-healing process. At the end of the treatment, the hematological index, blood biochemical parameters, paraoxonase (PON), arylesterase (ARE), and myeloperoxidase (MPO) activities in the fish blood samples were investigated. With regard to the hematological parameters, statistical differences were obtained except for mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) (P < 0.05). Enzyme activities (ARE, PON, and MPO), as well as some biochemical parameters (creatinin [Cre], alanine amino transferase, total glyceride, alkaline phosphatase, iron, calcium, low density lipoprotein-cholesterol [LDL-C], sodium, and potassium), were found to be importantly different among all groups at the P<0.05 level, while 8-hydroxydeoxyguanosine and caspase-3 levels were determined to be high in the pesticide group but decreased significantly in NAC-treated groups (P < 0.05). According to the results of the study, acute cysteine treatment showed an ameliorative effect on the hematological index, biochemical parameters, PON, MPO, and ARE in the blood in the all the treatment group fish. The positive effect of NAC on protein synthesis, detoxification, and diverse metabolic functions against cypermethrin toxicity was more effective in 1.0mM NAC. NAC has an important therapeutic effect on pesticide-induced hematoxicity for fish in terms of all the data. [ABSTRACT FROM AUTHOR]

This study evaluated the mitigating effects of dietary chlorogenic acid (CGA) on colon damage and the bacterial profile in a mouse model of dextran sulfate sodium (DSS)-induced colitis. C57BL/6J mice were randomly assigned to receive one of the following treatments: (i) basal diet; (ii) basal diet with 2% CGA; (iii) basal diet with 2.5% DSS or (iv) basal diet with 2% CGA and 2.5% DSS. Following a 2-week pre-treatment period, mice in the DSS and CGA-DSS groups received 2.5% DSS in drinking water for 5 days, while the other two groups received sterile water. Compared to DSS alone, CGA was found to reduce the disease activity index, myeloperoxidase activity and tumor necrosis factor-α levels in colon tissues (P < 0.05). CGA also ameliorated DSS-induced inflammatory responses, reduced colon shortening and decreased the histological scores (P < 0.05). In an evaluation of the relative abundances of bacteria in the fecal microbiota, we found that CGA reversed the decrease in diversity caused by DSS and improved the relative abundance of organisms in the genus Lactobacillus (P < 0.05). These results indicate that CGA maintains intestinal health and reduces DSS-induced colon injury by decreasing the production of pro-inflammatory cytokines and restoring intestinal microbial diversity. [ABSTRACT FROM AUTHOR]

Objective The interaction between neutrophils and activation of alternative complement pathway plays a critical role in the pathogenesis of ANCA-associated vasculitis (AAV). MPO, which can be released from ANCA-stimulated neutrophils, was recently demonstrated to be capable of activating the alternative complement pathway. Here we aimed to investigate the interaction between MPO and factor H (FH), a key regulator of the alternative pathway, and its effect on the functional activities of FH. Methods Detection of FH and MPO on neutrophil extracellular traps (NETs) induced by serum from AAV patients and in kidney biopsies of AAV patients was performed by immunostaining. In vitro binding between MPO and FH was examined by ELISA and surface plasmon resonance. The influence of MPO on the complement regulatory activity of FH was further assessed. Results FH deposited and co-localized with MPO in NETs. In kidney biopsies from AAV patients, MPO was closely adjacent to FH in glomerular capillaries. We demonstrated that MPO binds to FH with an apparent nanomolar affinity and identified short consensus repeats 1–4 of FH as the major binding sites. In terms of functional analysis, MPO inhibited the interaction between FH and C3b and the decay-accelerating activity of FH. The fluid phase and surface cofactor activities of FH upon C3b inactivation were inhibited by MPO. Conclusion Our findings indicate that MPO binds to FH and influences the complement regulatory activity of FH. MPO-FH interaction may participate in the pathogenesis of AAV by contributing to activation of the alternative complement pathway. [ABSTRACT FROM AUTHOR]

Iron deficiency is routinely treated with oral or systemic iron supplements, which are highly reactive and could induce oxidative stress via augmenting the activity of proinflammatory enzyme myeloperoxidase (MPO). To investigate the extent to which MPO is involved in iron-induced toxicity, acute (24 h) iron toxicity was induced by intraperitoneal administration of FeSO4 (25 mg/kg body weight) to MPO-deficient (MpoKO) mice and their wild-type (WT) littermates. Acute iron toxicity was also assessed in WT mice pretreated with an MPO inhibitor, 4-aminobenzoic acid hydrazide. Systemic iron administration up-regulated circulating MPO and neutrophil elastase and elevated systemic inflammatory and organ damage markers in WT mice. However, genetic deletion of MPO or its inhibition significantly reduced iron-induced organ damage and systemic inflammatory responses. In contrast to the acute model, 8 weeks of 2% carbonyl iron diet feeding to WT mice did not change the levels of circulating MPO and neutrophil elastase but promoted their accumulation in the liver. Even though both MpoKO and WT mice displayed similar levels of diet-induced hyperferremia, MpoKO mice showed significantly reduced inflammatory response and oxidative stress than the WT mice. In addition, WT bone-marrow-derived neutrophils (BMDN) generated more reactive oxygen species than MPO-deficient BMDN upon iron stimulation. Altogether, genetic deficiency or pharmacologic inhibition of MPO substantially attenuated acute and chronic iron-induced toxicity. Our results suggest that targeting MPO during iron supplementation is a promising approach to reduce iron-induced toxicity/side effects in vulnerable population. [ABSTRACT FROM AUTHOR]

Oesophageal adenocarcinoma is one of the most fatal tumours to affect the digestive tract and is the eighth most common malignancy worldwide. Gastro‐oesophageal reflux has an important role in the incidence of adenocarcinoma of the oesophagus. Gastro‐oesophageal reflux disease (GERD) is a multifactorial, acid‐peptic disorder that results from the reflux of noxious material from the stomach into the oesophagus. The refluxed material causes the occurrence of oesophageal inflammation which creates a condition that is called reflux oesophagitis. The prevalence of this disease has increased dramatically in recent decades, mostly in the western world, where it affects about 10% to 30% of the population. The aetiology of oesophageal mucosal damage is complicated. Many inflammatory mediators are produced within the gastrointestinal (GI) tract, but their contributions in pathophysiology and disease pathogenesis have not been well investigated. Despite the protective barrier provided by the oesophageal mucosa, refluxed materials can cause oxidative injury and in?ammatory responses that involve the epithelium and immune cells. The analysing cellular events in gastro‐ oesophageal reflux disease and physiological responses to such conditions are important and necessary for a better grasp of the pathogenesis of GERD and the expansion of new treatments. Therefore, we want to discuss some of the important and key factors of GERD disease in this article. [ABSTRACT FROM AUTHOR]