Serum Myeloperoxidase Research Articles

Active-Matrix Metalloproteinase-8, Myeloperoxidase in Relation With Periodontics, Preterm Birth.

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.

The Efficacy and Safety of Green-Lipped Mussel Extract Plus Ginkgo Biloba on Anti-Inflammatory Status in Patients with Knee Osteoarthritis

Background: Clinical research on the efficacy of nutraceutical compounds recommended for the relief of osteoarthritis (OA) symptoms has been largely disputed. In addition, no link has been established between its safety and efficacy in Kurdish population. The aim of this study is to determine the efficacy of New Zealand green-lipped mussel extract + Ginkgo biloba (GLME+) in patients with OA, and analyze the effect of GLME+ on inflammation. Methods: In an open-label, single-group allocation study, 40 patients diagnosed with knee OA were administrated 1000 mg/day of New Zealand green-lipped mussel extract and 100 mg/day of Ginkgo biloba for eight weeks. The outcome measure was scored using Western Ontario and McMaster Universities arthritis index (WOMAC). The serum concentration of inflammatory chemokine (CCL3) and myeloperoxidase (MPO) were measured. An intention-to-treat analysis was employed and subject data at T0 and T8 weeks. Results: Results showed a significant improvement in WOMAC score in post-treated OA patients with GLME+ (P&lt;0.001). In addition, CCL3 serum levels were significantly decreased after an 8-week intervention (P&lt;0.001). Moreover, no statistical significance was observed within groups in MPO serum levels (P&gt; 0.05). Conclusions: GLME+ improved knee joint pain, stiffness, and mobility in OA patients. Two of GLME+'s chondroprotective properties were the reduction of oxidative damage and the inhibition of inflammation, both of which have been linked to the etiology of OA cartilage destruction. The findings indicated that GLME+ may be useful in the treatment of OA patients.

Comparison of the Effects of Hesperidin Over 30- and 60-Day Intervals on Rainbow Trout: A Potential Biostimulant to Promote Growth, Immunological and Antioxidant Responses, and Disease Resistance

Abstract The current research evaluated the effects of dietary hesperidin (HSP) on growth parameters, digestive enzyme activities, innate immune markers, and antioxidant responses in rainbow trout, Oncorhynchus mykiss after the 30- and 60-day feeding trial. Then, specimens were subjected to Yersinia ruckeri infection for 14 days. For this, six hundred rainbow trout juveniles (initial weight; 25.49±0.40 g) were fed with different levels of HSP including 0 (HSP0; control), 50 (HSP50), 100 (HSP100), 150 (HSP150), and 200 (HSP200) mg/kg feed. After 60 days, dietary HSP100 supplementation significantly improved growth and feed efficiency indices. The optimal dose of HSP based on the regression test for WG and FCR detected 122 and 131 mg/kg, respectively. At the end of the 30th day, dietary HSP150 supplementation markedly boosted serum lysozyme (LYZ), myeloperoxidase (MPO), complement component C3, and immunoglobulin (Ig) levels, but decreased malondialdehyde (MDA) content. In the same period, dietary administration of HSP at the different concentrations markedly increased complement component C4 (HSP150 and HSP200), superoxide dismutase (SOD), skin mucus alkaline phosphatase (ALP) (HSP100–HSP200), skin mucus LYZ and catalase (CAT) (HSP100 and HSP 150), and skin mucus Ig level (HSP50–HSP200). After 60 days, all dietary HSP supplementation significantly improved lipase, serum C3, glutathione peroxidase (GPX), and skin mucus ALP, LYZ, and Ig levels, but decreased MDA, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) values. After 60 days, dietary administration of HSP150 induced a significant discrepancy in the activity of serum LYZ, MPO, respiratory burst (RB), and lactate dehydrogenase (LDH) compared to the control group. In the same period, dietary HSP supplementation at different levels induced a remarkable increase in digestive protease activity (HSP100), serum ACH50 and CAT activities (HSP100 and HSP150), skin mucus peroxidase and serum SOD levels (HSP100–HSP200), and serum C4 value (HSP50, HSP150, and HSP200), but markedly decreased ALP activity (HSP150 and HSP200). In addition, dietary HSP supplementation, especially HSP150, markedly boosted disease resistance against Y. ruckeri infection. The current data demonstrated that the oral administration of 100–150 mg/kg HSP has a high potential to promote growth performance, disease resistance, and faster induction of immune and antioxidant responses.

Determination of Serum Myeloperoxidase (MPO) and lactate dehydrogenase (LDH) as a tumour Marker in Chronic Myeloid Leukaemia (CML).

To evaluate the efficacy of serum myeloperoxidase and lactate dehydrogenase levels as tumour markers in chronic myeloid leukaemia patients after one-year treatment with tyrosine kinase inhibitors. The case-control study was conducted at the College of Medicine, Mustansiriyah University, Baghdad, Iraq, in collaboration with the National Centre of Haematology, Baghdad, from December 2019 to April 2020. The cases comprised chronic myeloid leukaemia patients aged ≥18 years who had completed one-year treatment with tyrosine kinase inhibitor. They were divided into two groups on the basis of major molecular response. Group 1 patients had major molecular response >0.1%, while group 2 patients had major molecular response <0.1%. Group 3 had healthy controls matched for age and gender. Serum myeloperoxidase and lactate dehydrogenase concentrations were measured using enzyme-linked immunosorbent assay. Data was analysed using SPSS 25. Of the 88 subjects, 32(36.4%) were in group A with mean age 44.9±12.6 years, 26(29.5%) were in group B with mean age 48.23±10.6 years, and 30(34%) were in group C with mean age 43.1±9.3 years. There was a significant increase in myeloperoxidase and lactate dehydrogenase levels in patient groups compared group 3 controls (p<0.05). Between the patient groups 1 and 2, the difference was significant for myeloperoxidase (p<0.05), but not for lactate dehydrogenase (p>0.05). There was higher oxidative stress in chronic myeloid leukaemia patients.

Liraglutide alleviates ferroptosis in renal ischemia reperfusion injury via inhibiting macrophage extracellular trap formation

Background and purposeRenal transplantation and other conditions with transiently reduced blood flow is major cause of renal ischemia/reperfusion injury (RIRI), a therapeutic challenge clinically. This study investigated the role of liraglutide in ferroptosis-associated RIRI via macrophage extracellular traps (METs). MethodsAnimal model with RIRI was established in C57BL/6J mice. A total of 72 C57BL/6J mice were used with 8 mice per group. Primary tubular epithelium was co-culture with RAW264.7 under hypoxia/reoxygenation (H/R) condition to mimic in vitro. Liraglutide was administrated into mice and cells. Extracellular DNA, neutrophil elastase and myeloperoxidase in serum and supernatant of cell medium were collected for measuring METs. F4/80 and citH3 were labeled to show METs. ResultsLiraglutide relieved RIRI and ferroptosis in vivo, and inhibited renal I/R-induced METs both in vivo and in vitro. F4/80 and citrullinated histone H3 (citH3) were highly co-localized after RIRI. Liraglutide attenuated the co-localization of citH3 and F4/80. Expressions of M2 markers were enhanced whereas these of M1 markers suppressed during liraglutide treatment in RIRI. Phosphorylation of signal transducer and activator of transcription (STAT)1, 3 and 6 were increased in RIRI mice and H/R-induced RAW264.7. However, liraglutide decreased phosphorylation of STAT1 and increased phosphorylation of STAT3 and STAT6. STAT3/6 inhibition reversed liraglutide-inhibited M1 polarization, extracellular traps and ferroptosis. ConclusionLiraglutide inhibited ferroptosis-induced renal dysfunction since it skewed macrophage polarization into M2 phenotype that interfered the formation of extracellular traps based on STAT3/6 pathway during RIRI. Liraglutide was proposed to be used for RIRI clinical treatment.

Зміни концентрації sST2, активності мієлопероксидази та iндуцибельної NO-синтази в сироватці крові та лімфоцитах як показник важкості перебігу захворювання у пацієнтів з артеріальною гіпертензією та на тлі коронавірусної хвороби

The prevalence of COVID-19 and its polymorphic clinical manifestations are attributed to a systemic inflammatory response, which also plays a key role in the development of arterial hypertension (AH). The prognosis and effectiveness of treatment in patients with AH and COVID-19 should be assessed based on the levels of inflammatory biomarkers sST2, myeloperoxidase, and iNOS. The aim of the work was to analyze the prognostic value sST2, myeloperoxidase and iNOS levels in the blood serum of patients with arterial hypertension (AH) and COVID-19. Methods. 2 groups of patients were examined: group 1- 36 patients with AH and hypertensive crisis. Group 2 – 35 patients with AH and polysegmental pneumonia on the background of COVID-19. The control group – 16 practically healthy individuals. All patients underwent anthropometry, determination of biochemical blood tests, echocardiography, level of sST2, and activity of iNOS and MPO using ELISA in blood serum and lymphocytes. Results. A 2.4-fold increase in sST2 content in blood serum was noted in AH and 2.9-fold in the background of COVID-19. The level of myeloperoxidase in blood serum increased 2.5 times in hypertension and 3.4 times in coronavirus disease. In lymphocytes, iNOS activity increased 3.25 times in hypertension and 4.3 times in COVID-19. sST2 level has a significant correlation with the size of the left atrium, left ventricle, and ejection fraction in patients with AH. A positive correlation with age was noted in the group of patients with AH and COVID-19. Conclusions. Levels of sST2, iNOS and myeloperoxidase are important markers of the severity of cardiovascular pathology, as well as in COVID-19 patients. In patients with arterial hypertension and in combination with COVID-19, a significant increase in the concentration of sST2, myeloperoxidase and iNOS was observed compared to practically healthy individuals. A significant elevation in myeloperoxidase levels has been noted in patients with AH without coronavirus disease, indicating the utility of its use as a highly sensitive marker for low-intensity inflammation, particularly in arterial hypertension. This makes this marker more promising for use than C-reactive protein.

Systematic evaluation supports the use of ELISA for quantification of calprotectin in equine feces, a first step toward noninvasive quantification of intestinal inflammation in horses.

To optimize and evaluate methods for the detection of the inflammatory biomarkers myeloperoxidase (MPO) and calprotectin (CP) in equine feces by ELISA. Healthy horses (n = 28) and horses with intestinal inflammation (n = 10). Feces were suspended in buffer to create fecal supernatant. Serum and fecal supernatant were analyzed using ELISA kits validated for the detection of MPO and CP in equine serum. Assay validation steps included intra- and interassay variability (coefficient of variation [CV]), dilution linearity, spike recovery, and sample type correlation. Variations in sample handling protocols (centrifugation speed, extraction buffer, and filtration) were evaluated. 17 paired fecal and serum samples were used for initial analysis (10 healthy horses, 7 colitis). Previously reported sample handling protocols resulted in detectable MPO and CP but poor CV, linearity, and spike recovery. There was a linear correlation between serum and fecal samples for CP but not MPO. There was a significant difference between the concentration and CV of alternative sample handling protocols for CP and MPO, with improved CV for CP (2.1% to 18.6%) but not MPO (14.4% to 53.4%). Processing fresh feces with a fecal extraction buffer and filtration of supernatant resulted in the best CV (0.5% to 3.8%) and recovery (45% to 64%) for CP. Detection of MPO was inconsistent regardless of method. There are few reliable diagnostic modalities for inflammation of the equine large colon. Findings support quantification of CP in equine feces using the described ELISA kit and protocol. With additional study to establish reference interval and clinical utility, the fecal inflammatory biomarker CP may allow for noninvasive quantification of intestinal inflammation in horses.

Effect of diets containing probiotic yeast Cystobasidium benthicum and fruit Cyrtocarpa edulis on growth and immune parameters of Nile tilapia (Oreochromisniloticus)

This study investigates Cystobasidium benthicum (Cb) probiotic yeast and Cyrtocarpa edulis (Ce) fruit dietary effects, single (0.5 %) or combined (Cb:Ce, 0.25:0.25 %), on growth performance, humoral immunity in serum and skin mucus, and intestinal morphology of Nile tilapia (Oreochromis niloticus) after 14 and 28 days. The Cb group presented the highest (P < 0.05) specific growth rate, weight gain, and absolute growth rate with respect to the control group. Immunological assays indicated that Cb, Ce and Cb:Ce groups increased serum nitric oxide concentration compared to the control group (P < 0.05). Cb and Cb:Ce groups showed the highest serum myeloperoxidase enzyme activity at day 14 and 28, respectively (P < 0.05); whereas, Cb:Ce group had the highest (P < 0.05) myeloperoxidase activity in skin mucus. The superoxide dismutase enzyme activity was unaffected. On day 28, Cb, Ce, and Cb:Ce groups showed higher and lower (P < 0.05) catalase enzyme activity in serum and skin mucus, respectively, compared with the control group. Only the Cb group had higher (P < 0.05) total protein concentration in serum (day 14) and skin mucus (day 14 and 28) with respect to the control group. The lysozyme activity in serum (day 28) and skin mucus (day 14) was higher (P < 0.05) in the Cb group compared to the control group. Only the skin mucus of Ce group showed bactericidal activity against Aeromonas dhakensis (P < 0.05). Histological studies indicated that Cb and Cb:Ce groups increased microvilli height, and Cb, Ce and Cb:Ce augmented goblet cell area at day 14 compared to the control group (P < 0.05). At day 28, microvilli height was higher in all groups and the number of intraepithelial leukocytes increased in Cb and Ce groups with respect to the control group (P < 0.05). The ex vivo assay revealed that A. dhakensis in leukocytes decreased cell viability similar to the control group (P < 0.05). A principal component analysis (PCA) confirmed the results. In conclusion, C. benthicum in the diet was the best supplement to improve the growth and immunity of Nile tilapia.

Zedoary turmeric oil injection ameliorates lung inflammation via platelet factor 4 and regulates gut microbiota disorder in respiratory syncytial virus-infected young mice

BackgroundRespiratory syncytial virus (RSV)-induced lung inflammation is one of the main causes of hospitalization and easily causes disruption of intestinal homeostasis in infants, thereby resulting in a negative impact on their development. However, the current clinical drugs are not satisfactory. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM), has been used for clinical management of inflammatory diseases. However, its in vivo efficacy against RSV-induced lung inflammation and the underlying mechanism remain unclear.PurposeThe present study was designed to confirm the in vivo efficacy of ZTOI against lung inflammation and intestinal disorders in RSV-infected young mice and to explore the potential mechanism.Study design and methodsLung inflammation was induced by RSV, and cytokine antibody arrays were used to clarify the effectiveness of ZTOI in RSV pneumonia. Subsequently, key therapeutic targets of ZTOI against RSV pneumonia were identified through multi-factor detection and further confirmed. The potential therapeutic material basis of ZTOI in target tissues was determined by non-target mass spectrometry. After confirming that the pharmacological substances of ZTOI can reach the intestine, we used 16S rRNA-sequencing technology to study the effect of ZTOI on the intestinal bacteria.ResultsIn the RSV-induced mouse lung inflammation model, ZTOI significantly reduced the levels of serum myeloperoxidase, serum amyloid A, C-reactive protein, and thymic stromal lymphoprotein; inhibited the mRNA expression of IL-10 and IL-6; and decreased pathological changes in the lungs. Immunofluorescence and qPCR experiments showed that ZTOI reduced RSV load in the lungs. According to cytokine antibody arrays, platelet factor 4 (PF4), a weak chemotactic factor mainly synthesized by megakaryocytes, showed a concentration-dependent change in lung tissues affected by ZTOI, which could be the key target for ZTOI to exert anti-inflammatory effects. Additionally, sesquiterpenes were enriched in the lungs and intestines, thereby exerting anti-inflammatory and regulatory effects on gut microbiota.ConclusionZTOI can protect from lung inflammation via PF4 and regulate gut microbiota disorder in RSV-infected young mice by sesquiterpenes, which provides reference for its clinical application in RSV-induced lung diseases.

A combined model of serum neutrophil extracellular traps, CD8+ Tcells, and tumor proportion score provides better prediction of PD-1 inhibitor efficacy in patients with NSCLC.

Immune checkpoint inhibitors provide a definite survival benefit for patients with driver-negative advanced non-small cell lung cancer (NSCLC), but predictors of efficacy are still lacking. There may be a relationship between immune inflammatory state and tumor immune response. We explored the relationship of serum neutrophil extracellular traps (NETs) with infiltrating cells in the tumor tissues of patients with NSCLC as well as their relationship with the therapeutic efficacy of programmed cell death protein 1 (PD-1) inhibitors. Serum myeloperoxidase (MPO)-double-stranded DNA (dsDNA) was detected as a marker of NET serum concentration. Tcells were detected by immunohistochemical staining, and neutrophils were counted by MPO immunofluorescence staining. Of the 31 patients with NSCLC, a longer progression-free survival after PD-1 inhibitor treatment was associated with higher levels of CD3+ Tcells, a lower neutrophil : CD3+-T-cell ratio (NEU/CD3+) and lower neutrophil : CD8+-T-cell ratio (NEU/CD8+) in tumor tissues. Patients with higher serum NETs were more likely to develop progressive disease after treatment (P = 0.003) and to have immune-related adverse events (IrAEs) as well as higher NEU/CD3+ and NEU/CD8+. The combined model of serum NETs, CD8+ Tcells, and tumor proportion score (TPS) significantly improved the prediction of PD-1 inhibitor efficacy [P = 0.033; area under the curve (AUC) = 0.881]. Our results indicate that serum NETs are effective predictors of PD-1 inhibitor response and reflect the tissue neutrophil-to-lymphocyte ratio and IrAE levels. The combined model of serum NETs, CD8+ Tcells, and TPS is a powerful tool for predicting the efficacy of PD-1 inhibitor treatment in patients with NSCLC.

Growth performance, health status, gut microbiome, and expression of immune and growth-related genes of rainbow trout (Oncorhynchus mykiss) fed diets with pea protein replacement of fish meal

The need for fish meal constrains fish farming and significantly impacts sustainability of the aquaculture industry. Hence, it is important to investigate the use of plant-based protein sources in fish diets. The present study was conducted to determine the effects of different levels of fish meal (FM) replacement by pea protein (PP) in a 60-day feeding experiment in rainbow trout, Oncorhynchus mykiss. Effects on growth performance, body composition, hematology, serum biochemistry and immunology, and immune (TNF-α, IL1-ß and Il-8) and growth-related (GH and IGFI) gene expression were investigated. Five experimental diets (45% protein and 20% lipid) differed in replacement level of FM by PP at rates of 0% (control (PP0)), 25% (PP25), 50%(PP50), 75%(PP75) and 100%(PP100). Fish were fed with experimental diets in triplicate twice daily. The best growth performance was obtained in PP0 and PP25 groups. While fat ratios of fish fillets significantly differed (p < 0.05), there was no significant effects on protein ratios (p < 0.05). There was no significant change in the hematological values of fish, except those fed the PP100 diets, which displayed a reduction in eyrthocyte counts, hemoglobin content and hematocrit. As PP supplementation increased fish showed elevated serum glucose, total protein, cholesterol and myeloperoxidase activity and decreased glutamic pyruvic transaminase and alkaline phosphatase activity. Fish fed diets with between 25 and 75% replacement showed a decline in lactic acid bacteria in the gut. Significant increases in expression were observed in the liver of the PP25 fish relative to the 0% control for all immune and growth-related genes except for IL1-ß. These data suggest that up to 25% of FM can be replaced by PP without any adverse effects on rainbow trout.

Serum myeloperoxidase, paraoxonase, and plasma asprosin concentrations in patients with acute myocardial infarction

IntroductionThe objective of this study was to evaluate the usefulness of the serum biomarkers myeloperoxidase (MPO), paraoxonase (PON), and plasma asprosin in acute myocardial infarction (AMI) diagnosis and assess their compatibility with routinely screened cardiac biomarkers. MethodsThis study was conducted using a prospective cross-sectional design and included 90 patients, consisting of 60 patients diagnosed with AMI (30 with ST-segment elevation and 30 with non-ST-segment elevation on ECG) and 30 controls (without a diagnosis of AMI). Changes in the levels of cardiac biomarkers (Hs-cTnI, CK, CK-MB), lipid profile (TC, TG, LDL, HDL), MPO, PON, asprosin, and routine biochemical parameters of patients were evaluated. Furthermore, receiver operating characteristic curve analysis revealed the diagnostic value of Hs-cTnI, MPO, PON, and asprosin in predicting AMI. Binary logistic regression analysis of cardiac marker concentrations was used to predict the presence of AMI. In contrast, multinomial logistic regression analysis was conducted to predict the type of AMI and the control group. ResultsThe median levels of MPO and plasma asprosin were found to be higher in the patient group (3.22 [interquartile range {IQR}: 2.4–4.4] ng/ml and 10.84 [IQR: 8.8–17.8] ng/ml, respectively) than in the control group (2.49 [IQR: 1.9–2.9] ng/ml and 4.82 [IQR: 4.6–8.0] ng/ml, respectively) (p = 0.001 and p < 0.001, respectively). The median levels of PON were 8.94 (IQR: 7.6–10.4) ng/ml in the patient group and 10.44 (IQR: 9.1–20.0) ng/ml in the control group (p < 0.001). In the binary logistic regression model, compared with the control group, a 1 ng/ml increase in MPO level increased the odds of having AMI by 3.61 (p = 0.041, 95% CI: 1.055–12.397), whereas a 1 ng/ml increase in asprosin level increased the odds of having AMI by 2.33 (p < 0.001, 95% CI: 1.479–3.683). In the multinominal logistic regression model, compared with the control group, a 1 ng/ml increase in the MPO level increased the odds of having NSTEMI by 4.14 (p = 0.025, 95% CI: 1.195–14.350), whereas a 1 ng/ml increase in asprosin concentrations increased the odds of having NSTEMI by 2.35 (p < 0.001, 95% CI: 1.494–3.721). ConclusionHerein, MPO and asprosin concentrations increased with Hs-cTnI, and a decrease in PON concentration indicated that oxidant–antioxidant parameters and adipokines were related to AMI pathogenesis.

Serum myeloperoxidase level as A marker of activity in patients with systemic lupus erythematosus with lupus nephritis class III and IV

Serum myeloperoxidase level as A marker of activity in patients with systemic lupus erythematosus with lupus nephritis class III and IV

Alteration of Serum Bilirubin and Myeloperoxidase Concentration Associated Moderate Intensity Exercise Among Novice Students Athletes

Alteration of Serum Bilirubin and Myeloperoxidase Concentration Associated Moderate Intensity Exercise Among Novice Students Athletes

Insight into antiphospholipid syndrome: the role and clinical utility of neutrophils extracellular traps formation

Antiphospholipid syndrome (APLS) is a systemic immune dysregulation distinguished by repetitive complications and pregnancy loss in the absence of definite etiology. Most research focuses on the laboratory detection and clinical features of APLS, but its precise etiology remains to be deeply explored. NETosis is a newly developed theory in the pathophysiology of APLS which may serve as the missing bridge between coagulation and inflammation reaching the disease progression and severity. We aimed in this study to navigate the prognostic role of NETosis in thrombotic APLS. Our study included 49 newly diagnosed APLS patients (both 1ry and 2ry) who met clinical and laboratory criteria as per the international consensus statement on the update of the classification criteria for definite APLS and were sub-classified according to the occurrence of thrombotic events in thrombotic and non-thrombotic types. In addition, 20 sex and age-matched reactive subjects and 20 sex and age-matched healthy volunteer controls were enrolled. NETosis formation was assessed by measuring serum Myeloperoxidase (MPO) and Histones level using the enzyme-linked immunosorbent assay (ELISA) technique. Both MPO and Histones levels were able to discriminate among APLS cases from normal controls, showing significant cutoffs of > 2.09 ng/ml for MPO and > 1.45 ng/ml for Histones (AUC values were 0.987and 1.000, respectively). These values can be used as predictors for NETosis pathophysiology in APLS patients. Additionally, these markers demonstrated a significant association with several prognostic indicators, including thrombosis, higher PT and INR, and lower hemoglobin (Hb) levels which are supposed to be ameliorated by using NETs inhibitors. In conclusion, we suggest that measuring NETosis markers, MPO, and Histones, in the early course of APLS using proposed cutoff values will facilitate the timely initiation of anti-NETosis therapy and improve the overall prognosis, particularly for patients with thrombotic APLS.

Improvement of high-density lipoprotein atheroprotective properties in patients with systemic lupus erythematosus after belimumab treatment.

Chronic inflammatory diseases, like Systemic Lupus Erythematosus (SLE), carry an increased risk for atherosclerosis and cardiovascular events, accompanied by impairment of atheroprotective properties of high-density lipoprotein (HDL). In SLE, serum BAFF (B cell-activating factor), a cytokine implicated in disease progression, has been correlated with subclinical atherosclerosis. We investigated the impact of treatment with belimumab -an anti-BAFF monoclonal antibody- on HDL atheroprotective properties and composition in SLE patients. Serum samples were collected from 35 SLE patients with active disease despite conventional therapy, before and after 6-month add-on treatment with belimumab, and 26 matched healthy individuals. We measured cholesterol efflux and antioxidant capacities, paraoxonase-1 activity, serum amyloid A1, myeloperoxidase and lipid peroxidation product levels of HDL. LC-MS/MS was performed to analyze the HDL lipidome. Following treatment with belimumab, cholesterol efflux and antioxidant capacities of HDL were significantly increased in SLE patients and restored to levels of controls. HDL-associated paraoxonase-1 activity was also increased, whereas lipid peroxidation products were decreased following treatment. HDL cholesterol efflux and antioxidant capacities correlated negatively with the disease activity. Changes were noted in the HDL lipidome of SLE patients following belimumab treatment, as well as between SLE patients and healthy individuals, and specific changes in lipid species correlated with functional parameters of HDL. HDL of SLE patients with active disease displays impaired atheroprotective properties accompanied by distinct lipidomic signature compared with controls. Belimumab treatment may improve the HDL atheroprotective properties and modify the HDL lipidomic signature in SLE patients, thus potentially mitigating atherosclerosis development.

Lactobacillus reuteri mitigates hepatic ischemia/reperfusion injury by modulating gut microbiota and metabolism through the Nrf2/HO-1 signaling.

This study seeks to investigate the impacts of Lactobacillus reuteri (L. reuteri) on hepatic ischemia-reperfusion (I/R) injury and uncover the mechanisms involved. Mice in the I/R groups were orally administered low and high doses of L.reuteri (L.reuteri-low and L. reuteri-hi; 1 × 1010 CFU/d and 1 × 1011 CFU/d), for 4 weeks prior to surgery. Following this, mice in the model group were treated with an Nrf2 inhibitor (ML-385), palmitoylcarnitine, or a combination of both. After treatment with L. reuteri, mice exhibited reduced levels of serum aminotransferase (ALT), aspartate aminotransferase (AST), and myeloperoxidase (MPO) activity, as well as a lower Suzuki score and apoptosis rate. L. reuteri effectively reversed the I/R-induced decrease in Bcl2 expression, and the significant increases in the levels of Bax, cleaved-Caspase3, p-p65/p65, p-IκB/IκB, p-p38/p38, p-JNK/JNK, and p-ERK/ERK. Furthermore, the administration of L. reuteri markedly reduced the inflammatory response and oxidative stress triggered by I/R. This treatment also facilitated the activation of the Nrf2/HO-1 pathway. L. reuteri effectively counteracted the decrease in levels of beneficial gut microbiota species (such as Blautia, Lachnospiraceae NK4A136, and Muribaculum) and metabolites (including palmitoylcarnitine) induced by I/R. Likewise, the introduction of exogenous palmitoylcarnitine demonstrated a beneficial impact in mitigating hepatic injury induced by I/R. However, when ML-385 was administered prior to palmitoylcarnitine treatment, the previously observed effects were reversed. L. reuteri exerts protective effects against I/R-induced hepatic injury, and its mechanism may be related to the promotion of probiotic enrichment, differential metabolite homeostasis, and the Nrf2/HO-1 pathway, laying the foundation for future clinical applications.

Efficacy of metamizole to prevent kidney injury after renal-ischaemic reperfusion injury in Wistar rats.

Renal ischaemia-reperfusion injury (RIRI) is a common kidney procedure complication due to temporary blood flow interruption, leading to kidney injuries. This study aimed to analyze the effect of metamizole on the levels of interleukin-18 (IL-18), neutrophil-gelatinase-associated lipocalin (NGAL), myeloperoxidase (MPO), and histopathological changes in rats with RIRI. Animal pre-clinical design study was used. Thirty-two male Wistar rats (Rattus norvegicus) were divided into four groups: negative control, positive control, M100, and M200. Blood samples were collected by intracardiac puncture, followed by bilateral nephrectomy and analyzed histopathologically. Significant difference in IL-18 levels between positive control vs negative control (114.1 + 12.07 vs. 94.0 + 11.4; P = 0.019) and positive control vs M100 (114.1 + 12.07 vs. 86.9 + 8.34; P = 0.007). There was no difference in NGAL. M100 group had the lowest serum MPO levels (14.78+2.01), there was a significant difference in MPO levels in all pairwise analyses. There was a difference in cumulative EGTI scores among the study groups [positive 10.5 (8-11) vs. negative 9 (7-10) vs. M100 9 (7-10) vs. M200 9 (7-11); P = 0.021]. Metamizole 100mg/kgBW can reduce IL-18 and MPO levels in RIRI, giving more optimal results without affecting NGAL levels. Metamizole administration can reduce cumulative EGTI scores in RIRI, both at doses of 100mg/kgBW and 200mg/kgBW. This study shows that Metamizole can be used to prevent kidney injury caused by RIRI. IL-18 and MPO can be biomarkers in predicting kidney injury in RIRI.

Protective effect of clotrimazole on lung injury in an experimental model of ruptured abdominal aortic aneurysm.

Lungs are the target organs most affected by ischemia/reperfusion (I/R) injury, which is exacerbated when hemorrhagic shock occurs. Suppressing various proinflammatory cytokines, inflammation and oxidation that initiate and aggravate lung damage with various drugs or methods provides significant benefits in preventing lung damage. This study aims to evaluate the protective effect of clotrimazole (CLT), an antimycotic drug, on lung injury and systemic inflammatory response in rats by creating an experimental model of a ruptured abdominal aortic aneurysm (RAAA). Thirty-six male Sprague Dawley rats were randomly divided into 5 groups: sham, sham+CLT, sham+polyethylene glycol (PEG), shock+ischemia/reperfusion (SIR), and SIR+CLT. Saline, CLT and PEG were administered in the sham groups without shock and I/R. The hemorrhagic shock was developed in SIR groups by drawing blood for 1 h to keep the mean arterial pressure at 50 mm Hg. After 60 min, the SIR+CLT group was given 20 mg/kg CLT; then, the aortic clamps were opened, and rats were left for 120 min of reperfusion. The blood taken to create hemorrhagic shock was returned in a controlled manner during this time. At the end of the reperfusion procedure, samples were taken for cytokine levels in serum and lung tissue and for other biochemical analyses. Blood gas, histopathological examination and wet/dry weight measurements were performed to assess lung injury. An increase was observed in all parameters in the SIR group compared to the sham group. In the SIR+CLT group, the serum myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-α), lung MPO values, histologically lung injury scores, and lung tissue wet/dry ratio were decreased significantly when compared to the SIR group (p < 0.05). These results indicate that CLT may reduce the systemic inflammatory response and lung injury due to shock and I/R in an experimental model of RAAA.

Cardiovascular and renal oxidative stress-mediated toxicities associated with bisphenol-A exposures are mitigated by Curcuma longa in rats.

Curcuma longa Rhizome (CLR), due to its potent antioxidant phytochemical constituents, was investigated for its effects on bisphenol A (BPA)-induced cardiovascular and renal damage. Sixty rats were randomly selected, and grouped as control, BPA (100 mg/ kg), BPA and CLR 100 mg/kg, BPA and CLR 200 mg/kg, CLR 100 mg/kg, and CLR 200 mg/kg for 21 days. Oxidative stress indices, antioxidant status, blood pressure parameters, genotoxicity, and immunohistochemistry were determined. Rats exposed to the toxic effects of BPA had heightened blood pressure, lowered frequency of micronucleated polychromatic erythrocytes, and decreased activities of antioxidant enzymes compared with rats treated with CLR. Moreover, administration of CLR significantly (p<0.05) lowered malondialdehyde content and reduced the serum myeloperoxidase activity. Immunohistochemical evaluation revealed significantly (p<0.05) increased expressions of cardiac troponin and Caspase 3 in the BPA group compared with the CLR-treated groups. C. longa ameliorated cardiotoxic and nephrotoxic actions of bisphenol-A via mitigation of oxidative stress, hypertension, and genotoxicity.