Myeloperoxidase Levels Research Articles

D-mannose alleviates chronic periodontitis in rats by regulating the functions of neutrophils

BackgroundPeriodontitis is a chronic inflammatory disease characterized by the destruction of the components of the periodontium. It significantly impacts oral health and has been linked to systemic conditions like cardiovascular disease and diabetes. The critical role of neutrophils in the occurrence and development of chronic periodontitis has been paid increasing attention. The study aimed to explore the protective effects of D-mannose on chronic periodontitis and determine whether its underlying mechanisms is related to neutrophils.MethodsTo explore the protective effects of D-mannose on chronic periodontitis, the eight-week-old Sprague Dawley rat model of lipopolysaccharide (LPS)-induced periodontitis was established, followed by D-mannose treatment by oral gavage. To evaluate the protective effects of D-mannose against periodontal bone loss, methylene blue staining, hematoxylin and eosin (H&E) staining, and micro-CT scanning were utilized. Then, immunofluorescence (IF), Western Blot, and RT-PCR were applied to assess the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and IL-17), anti-inflammatory cytokine (IL-10), tumor necrosis factor-alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), ten-eleven translocation 2 (TET2), and key glycolytic enzymes (HK1, HK2, PFKFB3), and to examine D-mannose’s impact on the recruitment and activation of neutrophils in the gingiva. Additionally, neutrophils isolated from the peripheral blood of healthy rats were treated with LPS and D-mannose, and changes in the expression levels of myeloperoxidase (MPO), IL-1β, IL-6, IL-17, IL-10, and TET2 were observed via IF.ResultsIn vivo, D-mannose inhibited LPS-induced alveolar bone resorption in rats. After D-mannose treatment, the expression levels of IL-17 (p<0.01) and TET2 (p<0.01) were suppressed by IF, and the expression levels of IL-1β (p<0.05), IL-17 (p<0.05) and TET2 (p<0.01) were downregulated by WB. The results of qPCR showed that D-mannose reduced the expression levels of IL-1β (p<0.05), IL-6 (p<0.01), IL-17 (p<0.01), TNF-α (p<0.01), G-CSF (p<0.01), GM-CSF (p<0.01), TET2 (p<0.01), HK1 (p<0.01), HK2 (p<0.01), and PFKFB3 (p<0.01). D-mannose also inhibited the recruitment and activation of neutrophils in LPS-treated rat gingival tissues. In vitro, the results of IF showed that D-mannose inhibited the activation of neutrophils stimulated by LPS, downregulated the expression of IL-1β (p < 0.05), IL-6, IL-17 (p < 0.01), and TET2 (p < 0.01), and upregulated the expression of IL-10 (p < 0.01).ConclusionsD-mannose can alleviate chronic periodontitis in rats by regulating the functions of neutrophils, potentially associated with the expression of TET2 and glycolysis, providing new insights into the potential application of D-mannose to chronic periodontitis.

High-dose atorvastatin and rosuvastatin reduce the levels of neutrophil extracellular trap-related proteins in coronary artery disease: association with prothrombotic state.

Neutrophil extracellular trap (NET) formation is involved in atherothrombosis. We sought to investigate whether statins affect neutrophil extracellular traps activation and release (NETosis) in coronary artery disease (CAD), and whether such changes show associations with statin‑induced additional effects. We studied 130 patients with advanced CAD before and at least 6 months after initiation of high‑dose statin therapy with rosuvastatin 40 mg/d or atorvastatin 80 mg/d. The levels of circulating citrullinated histone H3 (H3cit), myeloperoxidase (MPO), and neutrophil elastase (NE) were assessed as proteins associated with NETosis along with thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis inhibitors. Following statin therapy intensification, we observed reduced accumulation of H3cit (-30.4%), MPO (-28.1%), and NE (-25.5%; all P <0.001), all not associated with low‑density lipoprotein cholesterol (LDL‑C) lowering (-25%). However, H3cit level was lower in 50 patients (38.5%) who achieved the target LDL‑C below 1.8 mmol/l (-16.5%; P = 0.004), and in 19 patients (14.6%) with LDL‑C below 1.4 mmol/l (-25.5%; P = 0.001), as compared with the remaining individuals. The reductions in H3cit and MPO levels were associated with a 42.9% decrease in C‑reactive protein (CRP) level on high‑dose statins (R = 0.855; P <0.001 and R = 0.25; P = 0.004, respectively), along with increases in Ks and reduction in thrombin activatable fibrinolysis inhibitor (TAFI) activity, but not with CLT or thrombin generation (all |R|, 0.24-0.4; P <0.01). In multivariable analysis, changes in CRP (β = 0.771; P <0.001), TAFI activity (β = 0.125; P = 0.013), and fibrinogen level (β = 0.106; P = 0.034) were independently associated with a decrease in H3cit concentration. We showed for the first time that high‑dose statins can reduce the level of NET‑related proteins in association with anti‑inflammatory and antithrombotic actions in CAD patients.

Neutrophil extracellular traps, deoxyribonuclease and fibrosis in thoracic aortic aneurysm

Abstract Introduction Thoracic aortic aneurysm (TAA) is a rare but severe cardiovascular disease. The condition often goes undiagnosed, increasing the risk of acute aortic events. It is characterized by medial degeneration, caused by neutrophils infiltrating aortic tissue. Neutrophils can form proinflammatory and prothrombotic neutrophil extracellular traps (NETs), promoting disease progression. Purpose Recently, NETs and abdominal aortic aneurysm (AAA) were linked, while their effects on TAA development and progression remain unclear. We aimed to characterize NETs and NET-specific markers in tissue and plasma samples of TAA patients. Methods We included 171 patients with either ascending TAA (n=153) or Type A dissection (n=18). Healthy subjects were recruited as controls (n=135). Sample fiber composition was analyzed using trichrome; NET burden was quantified using immunofluorescence. Plasma NET surrogate markers including double-stranded (ds)DNA, myeloperoxidase (MPO), DNase activity and matrixmetalloproteinases (MMP) were measured using a fluorescence-based assay and ELISA, respectively. mRNA expression was assessed using qPCR. Results Median patient age was 65 years, and most were male (68.4%). Cardiovascular risk factors were common, including hypertension (77.8%), hyperlipidemia (57.9%), coronary artery disease (26.3%), and diabetes (18.7%). TAA patients were older with high BMI and impaired kidney function. Trichrome staining revealed abundant fibrotic material (median 47.99%), while collagen and elastic fiber distributions were 27.67% and 20.17%, respectively. TAA patients had increased amounts of aortic fibrotic material (47.99% vs 38.94%, p=0.001). Using immunofluorescence, we found higher NET expression in diseased tissue (0.87 [0.3, 1.85] vs 0.15 [0.03, 0.22]%, p=0.0017). This increase was primarily driven by the dissection patients (1.76 [0.89, 2.83]%, p=0.0037). Plasma MPO levels were increased in TAA compared to controls (36.93 [23.46, 57.55] vs 26.8 [19.7, 36.2]ng/mL, p&amp;lt;0.001), while DNase activity was decreased in patients (4.16 [2.66, 6.24] vs 6.06 [4.25, 8.11]mU/mL, p&amp;lt;0.001). Moreover, circulating plasma levels of MMP2 were elevated in TAA (250.36 [190.24, 351.32] vs 218.85 [171.32, 263.87]ng/mL, p=0.004). qPCR analysis of mRNA expressions in TAA cryospecimens revealed upregulations of TNFα (p=0.033) and CD45 (p=0.003), when compared to aortic disease-free controls. Conclusion Aortic fibrosis at the aneurysm site may be caused by inflammatory mechanisms involving TNFα and leucocytes (CD45+). High local NET-burden is indicative of activated neutrophils in the aortic media. TAA patients have suppressed DNase activity and higher MPO levels in venous blood, leading to dsDNA accumulation and increased neutrophil turnover. Elevated MMP2 suggests its involvement in TAA formation. Our findings could enable further research targeting NETs and inflammation in TAA, possibly finding novel therapies capable of mitigating aneurysm development.

Association of FTO variants rs9939609 and rs1421085 with elevated sugar and fat consumption in adult obesity

This cross-sectional study explores the impact of FTO gene single nucleotide polymorphisms (SNPs) rs9939609 and rs1421085 on dietary habits contributing to obesity risk in Thai adults. The study enrolled 384 participants from Bangkok, categorized as non-obese (BMI < 25 kg/m2) or obese (BMI ≥ 25 kg/m2) based on WHO Asia Pacific Guidelines. Genotyping for FTO variants was performed using DNA from blood samples. While both SNPs adhered to Hardy–Weinberg equilibrium, the association between risk alleles and anthropometric measurements was not statistically significant. However, risk allele carriers showed significantly higher intakes of sugar and saturated fat compared to homozygous dominant individuals. In the obese group, the odds ratio for high-sugar intake was 2.22 (95% CI 1.13–4.37, p = 0.021) for rs9939609 risk allele carriers. For high-saturated fat intake, the odds ratio was 1.86 (95% CI 1.02–3.40, p = 0.041). Similar associations were observed for rs1421085. Risk allele carriers also exhibited significantly higher leptin levels (p < 0.043) and a positive correlation with myeloperoxidase levels (p < 0.038). These findings highlight the complex relationship between FTO risk alleles, increased consumption of sugar and saturated fat, and obesity-related parameters. The insights emphasize the importance of considering both genetic and dietary factors in obesity prevention strategies.

Staphylea bumalda Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Regulating Inflammatory Cytokines, Oxidative Stress, and Maintaining Gut Homeostasis

Staphylea bumalda is a rare medicine and edible shrub native to the temperate regions of Asia, possessing significant medicinal potential. In this study, the components of S. bumalda tender leaves and buds extract (SBE) were analyzed and identified by HPLC and LC/MS method, and the safety of SBE was evaluated through mouse acute toxicity models. The protective effects of SBE on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice were investigated in terms of inflammatory factor levels, oxidative stress, and gut microorganisms. Results showed that hyperoside, kaempferol-3-O-rutinoside, isorhoifolin, and rutin were the main components of the extract, and SBE demonstrated good safety in experimental mice. SBE could alleviate weight losing, disease activity index (DAI) raising, and colon shortening in mice. Pathological section results showed that the inflammatory cell infiltration decreased significantly, and the number of goblet cells increased significantly in the SBE group. After SBE treatment, interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in serum were significantly decreased, and the levels of myeloperoxidase (MPO) and nitric oxide (NO) in colon tissues were significantly decreased. SBE inhibited gut inflammation by increasing Lactobacillus. In summary, SBE played a therapeutic role in UC mice by relieving colon injury, reducing inflammatory factor levels, and maintaining gut flora homeostasis. SBE is expected to become an auxiliary means to participate in the prevention and treatment of UC.

PTZ KINDLING MODEL: EVALUATION OF EEG FACTOR AND BIOCHEMISTRY PARAMETERS UNDER THE INFLUENCE OF RAMELTEON

Many selective synthetic melatonin receptor agonists have anticonvulsant/anti-epileptogenic properties. These agonists bind to melatonin receptor 1 (MT1) and receptor 2 (MT2), causing their activation. Therefore, we evaluated the anticonvulsant effect of Ramelteon (RMLT) as a melatonin agonist in the PTZ (Pentylenetetrazol)-kindling model. In the study, 36 male Wistar Albino rats were assessed in 6 groups (Sham, PTZ, dimethylsulphoxide (DMSO), Valproic acid (VPA) (150 mg/kg) + PTZ, RMLT (30 mg/kg)+PTZ, VPA+RMLT+PTZ). Cortical electroencephalography (EEG) data were recorded for all groups. Seizures were scored according to the Racine scale. Seizure scores and onset times of the first myoclonic movements were compared in EEG traces. Total antioxidant status (TAS), total oxidant status (TOS), catalase, myeloperoxidase (MPO), and Thiol levels were measured in serum samples. Also, Calcineurin (CaN), Neuropeptide-Y (NPY), Neuron Specific Enolase (NSE), and S100B levels were measured in brain tissue samples. There was a significant difference between the PTZ and PTZ+Valproic acid+RMLT groups for the onset of the first myoclonic movements and the rate of spikes in the EEG traces in Racine's convulsion stages (P 0.05). RMLT has anticonvulsant properties. Additionally, the receptor preference of RMLT can be investigated.

Can switching from cigarettes to heated tobacco products reduce consequences of pulmonary infection?

While tobacco industry data suggests that switching from combustible cigarettes to heated tobacco products (HTPs), like IQOS, may reduce the users' exposure to respiratory toxicants, it is not known if using HTPs impacts the outcomes of acute respiratory infections. Does switching from cigarettes to HTPs improve responses to pulmonary infection. We conducted experiments in which 3 groups of mice were pre-exposed to cigarette smoke for 8 weeks, followed by 8-week exposure to (1) HTPs (tobacco product switching), (2) air (smoking cessation), or (3) continued exposure to cigarette smoke. Pulmonary bacterial clearance and surrogate markers of lung damage were assessed as study outcomes. Significantly compromised clearance of bacteria from the lungs post-acute challenge occurred in both the switching group and in mice continuously exposed to cigarette smoke. Bacterial clearance, inflammatory T-cell infiltration into the lungs, and albumin leak improved at 12h post-acute challenge in the switching group compared to mice continuously exposed to cigarette smoke. Bacterial clearance, total lung immune-cell infiltration, inflammatory T-cell infiltration into the lungs, the content of total proteins in the BAL, and albumin leak measured post-acute challenge were compromised in the switching group compared to mice in the cessation group. Switching from cigarettes to HTPs did not improve lung myeloperoxidase and neutrophil elastase levels (markers for lung inflammation and damage), which, however, were significantly reduced in the cessation group. This study reveals only a modest improvement in respiratory infection outcomes after switching exposure from cigarettes to HTPs and significantly compromised outcomes compared to a complete cessation of exposure to all tobacco products.

Comparison of Dietary Supplementation with Krill Oil, Fish Oil, and Astaxanthin on an Experimental Ethanol-Induced Gastric Ulcer Model: A Biochemical and Histological Study

Background/Objectives: Despite advances in ulcer treatment research, the search for new, safe, and effective strategies for preventing and treating ulcer diseases persists. Methods: In this study, the protective effects of dietary supplementation with krill oil (KO), fish oil (FO), and astaxanthin (ASX) on an ethanol-induced gastric ulcer model were compared during biochemical and histological observations. Sprague–Dawley (n = 64) rats randomly divided into four groups—normal control (vehicle), KO, FO, and ASX groups—received the supplements via the orogastric route at a rate of 2.5% (v/w) of their daily feed consumption for 4 weeks. Then, ulcer induction was performed with ethanol. Results: The ulcer group showed increased levels of malondialdehyde (MDA), chemiluminescence (CL), and myeloperoxidase (MPO) activity and decreased levels of glutathione in the gastric tissues. While KO, FO, and ASX supplementation decreased chemiluminescence levels in the ulcer group, only ASX supplementation decreased MDA levels and MPO activity. Conclusions: In conclusion, supplementation with KO or FO has a similar protective effect against ethanol-induced ulcer damage, as it inhibits ROS formation and reduces lipid peroxidation. However, ASX supplementation has a higher protective effect than KO or FO supplementations against experimental ethanol-induced gastric lesions in rats, as it inhibits ROS formation and reduces neutrophil infiltration and lipid peroxidation.

Qingxin Jieyu Granule alleviates myocardial infarction through inhibiting neutrophil extracellular traps via activating ANXA1/FPR2 axis

BackgroundMyocardial infarction (MI), representing the most severe manifestation of coronary artery disease (CAD), stands as a primary concern in the prevention and management of cardiovascular diseases. Clinical evidence demonstrates that Qingxin Jieyu Granule (QXJYG) is efficacious in treatment of MI patients. However, the mechanisms underlying its therapeutic effects remain to be elucidated. PurposeThis study aimed to evaluate the effects of QXJYG on MI and investigate its underlying mechanisms. Materials and methodsThe MI model in rats was developed through ligating the left anterior descending (LAD) artery. The effect of QXJYG on cardiac function impairment in MI rats was assessed by echocardiography, while the improvement of cardiomyocyte morphology and myocardial fibrosis after treatment with QXJYG was evaluated through hematoxylin-eosin (H&E) staining and Masson staining. The chemical constituents of QXJYG in blood were identified by using the UPLC-Q-TOF/MS technique. Furthermore, the molecular mechanism underlying the QXJYG therapeutic effect in MI was postulated based on the disease gene-drug target network analysis. Other technical methods such as ELISA, immunohistochemical staining, Western Blot analysis and application of pharmacological inhibitors were employed to verify the effectiveness of QXJYG in treating MI and explore its potential molecular targets. ResultsThe cardiac function in experimental rats post-MI was significantly impaired, as evidenced by an enlarged infarction area, disordered arrangement of cardiomyocytes, and aggravated myocardial fibrosis. QXJYG treatment significantly enhanced the cardiac function and reduced the pathological damage of the cardiac tissue in MI rats. Through the network pharmacology analysis, we identified that FPR2 might be a potential target of QXJYG in its cardiac protection role. QXJYG markedly downregulated the level of neutrophil extracellular traps (NETs) in MI rats, specifically manifested as a significant reduction in the Histone-DNA level and expression of myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) proteins. Furthermore, QXJYG upregulated the levels of ANXA1 and FPR2 proteins in MI rats. The level of FPR2 was markedly reduced in MI rats upon administration of WRW4, a specific inhibitor of FPR2, which was associated with exacerbated MI injury and an elevated level of NETs. When WRW4 was co-administered with QXJYG, the cardioprotective effects of QXJYG on MI were significantly diminished. However, the addition of DNase I did not result in significant changes of the outcomes in MI rats after QXJYG intervention. ConclusionQXJYG treatment alleviates cardiac tissue injury in MI rats by inhibiting NETs through activating the ANXA1/FPR2 axis. The findings extend our understanding of the therapeutic effectiveness of QXJYG and offer a scientific foundation for the clinical utilization of QXJYG.

Role of miR-455-3p in the alleviation of LPS-induced acute lung injury by allicin

Acute lung injury (ALI) is a type of diffuse lung injury that seriously affects the survival of critically ill patients. MicroRNAs (miRNAs) can serve as promising therapeutic targets or offer insights for the development of potential therapeutic strategies against ALI. In our previous study, we demonstrated the protective effect of allicin in ALI, but the role of miRNAs in the alleviation of ALI by allicin remains unclear. This study aimed to investigate whether miRNAs mediate the effects of allicin on ALI. Cell viability and proliferation were determined using CCK-8 and EdU assays, respectively, while cellular apoptosis was analyzed by flow cytometry. The claudin-4 protein was detected by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting. The binding of miR-455 with claudin-4 was determined by bioinformatics analysis and validated by dual luciferase reporter assays. The lung wet/dry ratio of lipopolysaccharide (LPS)-treated rats was determined by hematoxylin and eosin (HE) and TUNEL staining of the pulmonary tissues. The levels of myeloperoxidase (MPO), interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α were determined by enzyme-linked immunosorbent assay (ELISA). We observed that allicin alleviated LPS-induced injury in A549 cells, and claudin-4 knockdown reversed the protective effect of allicin in ALI. Claudin-4 is a direct target of miR-455-3p, and miR-455-3p overexpression partially reversed the protective effect of allicin in LPS-treated A549 cells. Subsequent in vivo experiments confirmed that allicin protects against LPS-induced ALI by regulating the miR-455-3p/claudin-4 axis. The study revealed that the protective effect of allicin in ALI is mediated via miR-455-3p, which suppresses the expression of claudin-4.

Bacteriophage Therapy for Staphylococcus aureus Induced Postoperative Acute Endophthalmitis In Vivo

Background: Postoperative acute endophthalmitis is a rare but severe complication following cataract surgery, with bacterial pathogens such as Staphylococcus aureus being the leading cause. Despite declining incidence rates globally, visual outcomes remain poor in many cases. Recent studies have explored the potential of bacteriophage therapy to treat bacterial infections, particularly for antimicrobial-resistant strains. This study aimed to assess the therapeutic effectiveness of bacteriophage treatment in a rabbit model of S. aureus-induced acute postoperative endophthalmitis. Methods: The study employed a randomized, controlled, posttest-only design using New Zealand white rabbits. Following extracapsular lens extraction surgery, rabbits were injected with S. aureus intracamerally to induce endophthalmitis. The treatment group received additional bacteriophage therapy. Ocular inflammation was assessed by measuring two biomarkers, myeloperoxidase (MPO) and intercellular adhesion molecule-1 (ICAM-1), using enzyme-linked immunosorbent assay (ELISA) from vitreous fluid samples. Histopathological analysis of retinal and scleral structures was performed post-enucleation. Statistical analyses were conducted using independent t-tests. Results: The treatment group showed significantly lower ICAM-1 levels (p &lt; 0.001), indicating reduced leukocyte infiltration and inflammation compared to the control group. MPO levels were slightly elevated in the treatment group but were not statistically significant (p = 0.261). Histopathological examination revealed that retinal structures in the treatment group were preserved with reduced inflammatory cell infiltration, whereas the control group displayed extensive retinal damage, including neovascularization and retinal detachment. Conclusion: Bacteriophage therapy significantly reduced ocular inflammation and tissue damage in S. aureus-induced endophthalmitis, as evidenced by lower ICAM-1 levels and better-preserved retinal structures in the treatment group. These findings suggest that bacteriophage therapy may be an effective alternative to conventional treatments for postoperative acute endophthalmitis, particularly in cases involving antibiotic-resistant bacteria. Further studies are warranted to explore its broader clinical applicability.

Metabolic Syndrome, Inflammation, Oxidative Stress, and Vitamin D Levels in Children and Adolescents with Obesity.

Metabolic syndrome (MetS) is associated with systemic inflammation, oxidative stress, and hypovitaminosis D. Our aim was to determine whether vitamin D mediates inflammation and oxidative stress, assessed through selected biomarkers, in children with obesity and/or MetS. Eighty children with normal weight, overweight, or obesity were analyzed for serum vitamin D, C-reactive protein, leukocytes, adiponectin, monocyte chemoattractant protein-1, myeloperoxidase, interferon-inducible T-cell alpha chemoattractant (I-TAC/CXCL11), superoxide dismutase-1, fasting lipid and glucose levels, ultrasound-measured abdominal fat thickness, waist circumference, body mass index and blood pressure. Children with obesity or overweight had lower vitamin D levels, increased blood pressure, visceral and subcutaneous fat thickness, and higher leukocytes, C-reactive protein, and myeloperoxidase levels. Those with MetS also had lower adiponectin levels. Vitamin D levels are negatively correlated with body mass index, waist circumference, and visceral and subcutaneous fat thickness. Correlation, mediation, and regression analyses showed no link between vitamin D and inflammatory/oxidative stress variables. The novel biomarker I-TAC did not correlate with obesity or vitamin D status. Our results indicate that vitamin D does not significantly mediate inflammation or oxidative stress in children and adolescents with obesity and/or MetS. Selected inflammation/oxidative stress biomarkers appear to be altered primarily due to obesity rather than vitamin D status.

Role of CD64 and myeloperoxidase as biomarkers for early diagnosis of sepsis in pediatric intensive care unit

Globally, sepsis is the primary cause of death for children. While research conducted on adults has a significant impact on the diagnosis and treatment of sepsis in newborns and young children, there are significant factors that are pertinent to pediatrics as well. This prospective case-control study was conducted during the period from August 2020 to October 2022 after approval by the institutional ethical committee. The study included 48 critically ill children admitted at the Pediatric intensive care unit and 30 apparently healthy children as a control group. Laboratory investigations including complete blood picture, C-reactive protein (CRP), blood culture and sensitivity and plasma level of cluster of differentiation 64 (CD64) and myeloperoxidase (MPO) were investigated for all participants. A daily follow up for the signs of systemic inflammatory response syndrome (SIRS) or sepsis was done, and the patients were divided into SIRS and non-SIRS subgroups then patients were divided into two groups according to the presence of severe sepsis. A follow up CD64 and MPO sample were withdrawn from them to assess their prognostic value. SIRS was reported in 39.58 % of patients while severe sepsis was reported in 20.8%. CD64 and MPO were significantly higher in cases than controls (p= 0.003, p&lt;0.001, respectively) and, in patients with SIRs and severe sepsis CD64 was 1559.00± 367.09 pg/ml and 1547.9 4± 436.14 pg/ml, respectively. Also, MPO was significantly higher in patients with SIRS (113.58± 25.19 mU/ml) and severe sepsis (111.70± 26.50 mU/ml). CD64 and MPO significantly increased after development of sepsis in admitted patients. ROC was significantly higher for CD64 and MPO at admission than that for CRP at admission (p=0.123, p=0.014, respectively). In conclusion, plasma level of CD64 and MPO in peripheral blood can be considered an early sensitive marker for the detection and follow up of pediatric sepsis.

Pharmacological efficacy study of the cardio-cerebral stasis transforming medicines on cerebral ischemia and myocardial infarction in rats

The purpose of this study was to investigate the efficacy and mechanisms of cardio-cerebral stasis transforming medicines (CCSTM) against cerebral infarction (CI) and myocardial infarction (MI). CI modeling was conducted using the refined Longa suture-occluded technique, while MI modeling was accomplished through the occlusion of the anterior descending branch of the left coronary artery. We found that compared with the model groups, CCSTM decreased the infarct size in models of CI and MI in a dose-dependent manner. After brain ischemia, CCSTM decreased the level of myeloperoxidase (MPO) and malondialdehyde (MDA), and increased the level of superoxide dismutase (SOD). Besides, CCSTM reduced the concentrations of lactate dehydrogenase (LDH), malondialdehyde MDA, and endothelin (ET) in the plasma of rats injured with MI. Histological examination of brain sections revealed that CCSTM alleviated cerebral damage after ischemia compared with the model group. CCSTM can reduce myocardial and cerebral infarction injury, and the oxidation level after myocardial and cerebral infarction in rats.

Neoastilbin ameliorates sepsis-induced liver and kidney injury by blocking the TLR4/NF-κB pathway.

Sepsis frequently causes systemic inflammatory response syndrome and multiple organ failure in patients. Neoastilbin (NAS) is a flavonoid that plays vital functions in inflammation. This work aims to investigate the protective effects of NAS against sepsis-induced liver and kidney injury and elucidate its underlying mechanisms. The mouse model was established using cecal ligation puncture (CLP) induction. NAS was given to mice by gavage for 7 consecutive days before surgery. Liver and kidney function, oxidative stress, and inflammatory factors in serum or tissues were examined by ELISA or related kits. The expression of relevant proteins was assessed by Western blot. Hematoxylin and eosin and/or periodic acid-Schiff staining revealed that NAS ameliorated the pathological damage in liver and kidney tissues of CLP-induced mice. NAS improved liver and kidney functions, as evidenced by elevated levels of blood urea nitrogen, Creatinine, ALT, and AST in the serum of septic mice. TUNEL assay and the expression of Bcl-2 and Bax showed that NAS dramatically reduced apoptosis in liver and renal tissues. NAS treatment lowered the levels of myeloperoxidase and malondialdehyde, while elevated the superoxide dismutase content in liver and kidney tissues of CLP-induced mice. The levels of inflammatory cytokines (IL-6, TNF-α, and IL-1β) in the serum and both tissues of CLP-injured mice were markedly decreased by NAS. Mechanically, NAS downregulated TLR4 expression and inhibited NF-κB activation, and overexpression of TLR4 reversed the protective effects of NAS against liver and kidney injury. Collectively, NAS attenuated CLP-induced apoptosis, oxidative stress, inflammation, and dysfunction in the liver and kidney by restraining the TLR4/NF-κB pathway.

Immunohistochemical expression of netosis markers (MPO, H2A, H2B) in placenta of RPL women in Basrah Province

Background. Recurrent Pregnancy Loss (RPL) is a multifactorial disorder significantly impacting women’s health globally. Emerging research has implicated Neutrophil Extracellular Traps (NETs) in the pathophysi­ology of RPL, suggesting an immunological underpinning to miscarriage occurrences. Aim. The study aim to evaluate the role and expression of NETosis markers (MPO, histones H2A, H2B) in women with RPL in comparison to pregnant women. Methods. This prospective cohort study, conducted from January 2022 to July 2023, included 30 participants (20 RPL patients and 10 controls) from Al Basrah Maternity and Child Hospital. Immunohistochemical technique were employed to detect Myeloperoxidase and histones in placental samples. Statistical analysis was performed using SPSS, with significance set at p&lt;90.05. Results. Immunohistochemical analysis of placental tissues indicated significant overexpression of Myelo­peroxidase (MPO), and histones H2A and H2B, in RPL patients compared to control, emphasizing the potential involvement of NETs in placental pathology associated with miscarriage. The expression levels of MPO were positive in 80% of RPL patients but undetected in control (p = 0.0001). Histone expressions also differed significantly, with H2A detected in 55% of RPL patients compared to none in control (p = 0.001) and H2B in 70% versus 30% (both p &lt;0.001).

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.

Exploring the hepatoprotective potential of the probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide-postbiotic on ibuprofen-induced acute liver injury in rats.

The present study investigates the hepatoprotective effect of a probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide (EPS) against ibuprofen-induced acute liver injury, and to explore the involved underlying mechanisms. Hepatotoxicity was induced by administration of a single dose of ibuprofen (200 mg/kg body weight). The Lpb. plantarum E1K2R2 (109 CFU) and its EPS (200 mg/kg bw) were separately used to feed rats for seven consecutive days before ibuprofen administration. Liver toxicity was assessed by monitoring levels of serum liver enzymes, liver relative weight, oxidative stress and inflammatory markers, and through histopathological analysis. The results showed that ibuprofen administration significantly increased (P < 0.05) liver relative weight, elevated levels of alanine-amino transferase (ALT), aspartate-amino transferase (AST), decreased hepatic gluthatione (GSH) and endogenous antioxidant enzymes including, superoxide dismutase (SOD), catalase (CAT) and increased malondialdehyde (MDA) levels, nitric oxide (NO) and myeloperoxidase (MPO) in hepatic tissues. However, pre-treatment with Lpb. plantarum E1K2R2 and its EPS significantly attenuated these toxicity manifestations. Both pre-treatments restored liver weight, normalized transaminase enzyme levels, enhanced the activity of liver antioxidant enzymes (SOD and CAT), increased GSH content, and significantly reduced NO, MPO and MDA levels (P < 0.05), indicating their protective role against oxidative stress and inflammatory response induced by ibuprofen. Furthermore, histopathological analysis confirmed regular liver morphology in rats pre-treated with the probiotic and its EPS. These findings highlight the potential effectiveness of the probiotic Lpb. plantarum E1K2R2 and its EPS in mitigating ibuprofen-induced liver toxicity.

Combined Treatment with Tauroursodeoxycholic Acid and SCD Probiotics Reduces Oxidative Stress in Lung Tissue of Aged Rats

Aging is associated with an increased level of oxidative stress, resulting from an elevated production of reactive oxygen species, which can lead to cellular and tissue damage, particularly in the lungs. This study examined the effects of Tauroursodeoxycholic acid (TUDCA) and SCD Probiotics, both individually and in combination, on oxidative stress markers in the lung tissue of aged Sprague-Dawley rats. The primary objective was to assess the potential of these agents in reducing malondialdehyde (MDA), advanced oxidation protein products (AOPP), and myeloperoxidase (MPO) levels, which are indicative of oxidative damage and inflammation. The results showed that TUDCA significantly decreased MDA and AOPP levels, suggesting its role in maintaining mitochondrial stability and inhibiting apoptotic pathways. SCD Probiotics also demonstrated a reduction in AOPP levels, highlighting their immunomodulatory and antioxidant effects. Furthermore, the combined treatment of TUDCA and SCD Probiotics led to a more pronounced decrease in both MDA and AOPP levels, along with a significant reduction in MPO activity. This suggests a synergistic interaction that enhances the antioxidative and anti-inflammatory properties of the individual treatments. These findings support the therapeutic potential of TUDCA and SCD Probiotics in mitigating oxidative damage in aging lung tissues, proposing that their concurrent use could be an effective strategy against age-related oxidative stress. Further research is warranted to explore these effects across different models and long-term applications.

Cynaropicrin attenuates inflammatory cytokines in LPS‐induced RAW264.7 cells and ovalbumin‐induced asthmatic mice

AbstractThis study examines the anti‐inflammatory activity of cynaropicrin against lipopolysaccharide (LPS) in vitro and ovalbumin (OVA)‐challenged asthma in mice. Cynaropicrin's antimicrobial effects were tested on Escherichia coli (E. coli) and Streptococcus pyogenes (S. pyogenes) using the disc diffusion technique. Cytotoxicity was assessed with an (3‐(4, 5‐dimethylthiazolyl‐2)‐2, 5‐diphenyltetrazolium bromide) assay. The anti‐inflammatory property was evaluated in LPS‐induced RAW264.7 cells, while OVA‐challenged asthmatic mice were treated with 10 mg/kg of cynaropicrin. Key inflammatory and antioxidant markers were quantified, and lung histology was examined to confirm therapeutic roles. The antimicrobial studies proved that cynaropicrin effectively inhibited the growth of E. coli and S. pyogenes. Cynaropicrin displayed no cytotoxicity on RAW264.7 cells. Furthermore, it significantly inhibited inflammatory cytokine synthesis upon LPS induction. Cynaropicrin treatment decreased the inflammatory cell counts and also suppressed specific allergic markers in OVA‐challenged mice. It also decreased nitric oxide and myeloperoxidase levels and reduced pulmonary edema. Cynaropicrin increased antioxidant levels and decreased proinflammatory cytokines in the asthmatic mice. Lung histological examination confirms the ameliorative potency of cynaropicrin against OVA‐induced asthmatic pulmonary inflammation in mice. Our findings suggest cynaropicrin possesses significant ameliorative potency against allergen‐induced pulmonary inflammation.