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Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.
De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.
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Animaux , Rats , Extraits de plantes/administration et posologie , Croton/composition chimique , Inflammation/traitement médicamenteux , Anti-inflammatoires/administration et posologie , Antioxydants/administration et posologie , Phénols/analyse , Extraits de plantes/composition chimique , Feuilles de plante , Modèles animaux de maladie humaine , Anti-inflammatoires/composition chimique , Antioxydants/composition chimiqueRésumé
Introducción: La diabetes mellitus tipo 2 se caracteriza por la hiperglucemia debido a la insuficiente producción de insulina de las células β. La mieloperoxidasa promueve el estrés oxidativo durante la inflamación y la ceruloplasmina se considera su inhibidor endógeno. Objetivo: Evaluar la relación entre la ceruloplasmina y la mieloperoxidasa, determinadas simultáneamente en el suero de pacientes diabéticos tipo 2. Métodos: Se estudiaron 362 pacientes diabéticos tipo 2 y 110 sujetos sanos. La actividad sérica de la ceruloplasmina se determinó por el método de Siotto; y el de la mieloperoxidasa, por el de Kraeisz. Resultados: El 72 % de los pacientes diabéticos tenían hiperglucemia y el 77 % presentaba obesidad abdominal. Las actividades de ambas enzimas se incrementaron significativamente en relación con el grupo control. El coeficiente de correlación de la actividad enzimática resultó bajo. El cociente RMPO/CP de los pacientes diabéticos superó el de los controles. La ceruloplasmina no inhibió la mieloperoxidasa. Conclusiones: Predominó la mieloperoxidasa, por tanto, no se manifestó el efecto inhibitorio de la ceruloplasmina. La elevada actividad de la mieloperoxidasa se asocia con un agravamiento del cuadro clínico del paciente diabético.
Introduction: Type 2 diabetes mellitus is characterized by hyperglycemia due to insufficient insulin production by β cells. Myeloperoxidase promotes oxidative stress during inflammation and ceruloplasmin is considered its endogenous inhibitor. Objective: To evaluate the relationship between ceruloplasmin and myeloperoxidase, determined simultaneously in the serum of type 2 diabetic patients. Methods: A total of 362 type 2 diabetic patients and 110 healthy subjects were studied. Serum ceruloplasmin activity was determined by the Siotto KM method and myeloperoxidase by the Kraeisz JE method. Results: 72% of diabetic patients had hyperglycemia and 77% had abdominal obesity. The activities of both enzymes were significantly increased relative to the control group. The correlation coefficient of enzyme activity was low. The ORMO/CP ratio of diabetic patients exceeded that of controls. Ceruloplasmin did not inhibit myeloperoxidase. Conclusions: Myeloperoxidase predominated, therefore, the inhibitory effect of ceruloplasmin was not manifested. The high activity of myeloperoxidase was associated with a worsening of the clinical picture of the diabetic patient.
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Objective To ascertain the efect of human immunodefciency virus (HIV) infection, as well as, antiretroviral therapy (ART) on neutrophil oxidative burst in children. Methods Fifty-fve children living with HIV infection (30 receiving ART for?2 y, 25 treatment-naïve) and 30 healthy controls, aged 18 mo–18 y, were assessed for hemogram and neutrophil oxidative burst. The treatment-naïve children were followed up and the above tests were repeated after 6 mo of ART. Results Mean (SD) serum MPO activity at 6 mo after ART [32.1 (±19.9) U/L] was comparable to that at disease onset [17.2 (±23.0) U/L], although it was signifcantly higher compared to that in children on ART?2 y [13.3 (±15.8) U/L] and controls [12.1 (±11.9) U/L]. Median fuorescence intensity (MFI) of unstimulated DHR was highest at 6 mo after ART and in the treatment-naïve group, which was signifcantly higher than in the controls, as well as, children receiving ART?2 y. Stimulation index was highest in the control group [442.4 (341.9–562.9)], which was comparable to that in children on ART?2 y [304.2 (153.2–664.8)], but was signifcantly higher than the treatment-naïve cohort [266.1 (148.2–339.4)] and children on ART for 6 mo [318.8 (154.9–395.6)]. Conclusion A hyperinfammatory state caused by an increased serum myeloperoxidase enzyme activity and increased basal neutrophil oxidative burst was seen in untreated HIV infection and during initial 6 mo of ART. ART given for?2 y normalized the impaired neutrophilic phagocytic functions.
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Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.
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ObjectiveTo explore the clinical effect of Tiaoxin formula in the treatment of patients with coronary heart disease and anxiety/depression and its impact on serum levels of 5-hydroxytryptamine (5-HT), β- thromboglobulin (β-TG) and myeloperoxidase (MPO). MethodA total of 66 patients with coronary heart disease and anxiety/depression were randomly divided into the Tiaoxin formula group and Deanxit group, 33 cases in each group. Both groups were given fundamental western treatment for coronary heart disease. Additionally, the Deanxit group was treated with flupentixol and melitracen tablets and the Tiaoxin formula group was treated with Tiaoxin Formula. The treatment lasted 8 weeks. Before and after treatment, the changes of clinical efficacy, Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7) scale, Seattle Angina Questionnaire (SAQ), heart rate variability, and serum 5-HT, β-TG and MPO levels, and incidence of adverse reactions in the two groups were observed. ResultThere was no significant difference in the baseline indexes of patients in the two groups, and thus the two groups were comparable. After treatment for 8 weeks, the total effective rate for traditional Chinese medicine (TCM) syndromes in the Tiaoxin Formula group was 87.88% (29/33) higher than 63.64% (21/33) in the Deanxit group (Z=-2.653, P<0.05). Compared with those before treatment, the PHQ-9 and GAD-7 scores of the two groups were decreased at week 4 and 8 of treatment (P<0.05), and there was no statistical difference between two groups. And the SAQ dimension scores of the two groups were increased at week 4 and 8 of treatment (P<0.05). Compared with the Deanxit group, the Tiaoxin Formula group had elevation in two dimension scores: Physical limitation and angina stability (P<0.05). Compared with the conditions before treatment, the serum 5-HT level in the two groups were increased, while the β-TG and MPO levels were lowered (P<0.05), and there was no distinct difference between two groups. In addition, the standard deviation of normal-to-normal intervals (SDNN) and standard deviation of average normal-to-normal intervals (SDANN) of the heart rate variability in the Tiaoxin formula group were elevated after treatment (P<0.05), which were more significant than those of the Deanxit group (P<0.05). During the treatment period, the incidence of adverse drug reactions in the Tiaoxin formula group was lower than that in the Deanxit group (P<0.05), and no adverse events were observed in the two groups. ConclusionTiaoxin formula was effective for the treatment of patients with coronary heart disease accompanied by anxiety and depression, which improved the clinical symptoms, increased serum 5-HT levels, and decreased serum β-TG and MPO levels, and had few adverse reactions and high safety for patients, showing a high clinical value.
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Objective To explore the beneficial effects and mechanisms of neutrophil elastase (NE) and myeloperoxidase (MPO) on lead-induced hepatic inflammation in mice. Methods The specific pathogen free male C57BL/6 mice were randomly divided into four groups: control group, lead-exposed group, NE inhibitor group, and MPO inhibitor group, with three mice in each group. The mice in lead-exposed group, NE inhibitor group, and MPO inhibitor group were intraperitoneally injected with a dose of 10 mg/kg body mass of lead acetate solution, while the mice of control group received an equal volume of 0.9% saline three times per week for four weeks. In the last seven days, mice in both inhibitor groups were intraperitoneally injected with a dose of 40 mg/kg NE inhibitor sivelestat sodium or MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) once per day. Mouse body weight and liver histopathological changes were observed. The mRNA expression of genes associated with inflammation, such as tumor necrosis factor-α (Tnfa), interleukin-1β (Il1b), interleukin-6 (Il6), and nucleotide-binding oligomerization domain-like receptor protein 3(Nlrp3), apoptosis-associated speck-like protein (Asc) and cysteinyl aspartate specific proteinase (Caspase1) in the mouse liver tissues was detected by real-time quantitative polymerase chain reaction. The protein expression of NLRP3, ASC, and CASPASE-1 was detected using Western blotting. Results The activities of mice in all four groups were generally normal, and there was no significant difference in body weight (P>0.05). The results of hematoxylin-eosin staining showed that the cell size of hepatocytes varied in the lead-exposed mice, with indistinct cell boundaries, indicating early inflammatory responses in liver tissues. After intervention with NE or MPO inhibitors, the early inflammatory responses improved in the liver tissues of the mice in both inhibitor groups, with a better improvement observed in MPO inhibitor group compared with the NE inhibitor group. The mRNA expression of Tnfa, Il1b, Il6, Nlrp3, Asc, and Caspase1, as well as the protein expression of ASC, and CASPASE-1 in the livers of mice in the lead-exposed group was higher compared with those in the control group (all P<0.05). Compared with the lead-exposed group, the relative mRNA expression of Tnfa, Il1b, Il6, Nlrp3 and Asc was decreased in the liver tissues of mice in the NE inhibitor group (all P<0.05), while the relative expression of mRNA of Tnfa, Il1b, Il6, Caspase1 and the protein expression of ASC and CASPASE-1 were decreased in the liver tissues of mice in the MPO inhibitor group (all P<0.05). Conclusion Lead induce hepatic inflammation in mice by activating NLRP3 inflammasome. The inhibition of NE or MPO improve the lead-induced hepatic inflammatory responses in mice by alleviating NLRP3 inflammasome activation.
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Prevention and treatment of complications after liver transplantation play a significant role in maintaining liver graft function and improving clinical prognosis of the recipients. Neutrophil extracellular trap (NET) are fibrous net-like structures composed of DNA as the skeleton and histones and granular proteins released by activated neutrophils. Studies have shown that the activation of neutrophils and the release of NET in donor liver after liver transplantation are involved in the incidence of multiple liver transplantation-related complications including ischemia-reperfusion injury, acute rejection, acute liver failure and recurrence of hepatocellular carcinoma, etc. In this article, the effect of NET on the complications after liver transplantation was mainly assessed, and research progress on NET as a potential target for the prevention and treatment of complications after liver transplantation was reviewed, aiming to provide reference for the prevention and treatment of complications after liver transplantation, enhance clinical efficacy of liver transplantation and improve clinical prognosis of the recipients.
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Abstract Cryptosporidiosis is a waterborne protozoal infection that may cause life-threatening diarrhea in undernourished children living in unsanitary environments. The aim of this study is to identify new biomarkers that may be related to gut-brain axis dysfunction in children suffering from the malnutrition/infection vicious cycle is necessary for better intervention strategies. Myeloperoxidase (MPO) is a well-known neutrophil-related tissue factor released during enteropathy that could drive gut-derived brain inflammation. We utilized a model of environmental enteropathy in C57BL/6 weanling mice challenged by Cryptosporidium and undernutrition. Mice were fed a 2%-Protein Diet (dPD) for eight days and orally infected with 107-C. parvum oocysts. C. parvum oocyst shedding was assessed from fecal and ileal-extracted genomic DNA by qRT-PCR. Ileal histopathology scores were assessed for intestinal inflammation. Prefrontal cortex samples were snap-frozen for MPO ELISA assay and NF-kb immunostaining. Blood samples were drawn by cardiac puncture after anesthesia and sera were obtained for serum amyloid A (SAA) and MPO analysis. Brain samples were also obtained for Iba-1 prefrontal cortex immunostaining. C. parvum-infected mice showed sustained stool oocyst shedding for six days post-infection and increased fecal MPO and inflammation scores. dPD and cryptosporidiosis led to impaired growth and weight gain. C. parvum-infected dPD mice showed increased serum MPO and serum amyloid A (SAA) levels, markers of systemic inflammation. dPD-infected mice showed greater MPO, NF-kB expression, and Iba-1 immunolabeling in the prefrontal cortex, an important brain region involved in executive function. Our findings suggest MPO as a potential biomarker for intestinal-brain axis dysfunction due to environmental enteropathy.
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OBJECTIVES@#Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality.@*METHODS@#The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality.@*RESULTS@#A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801).@*CONCLUSIONS@#PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.
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Humains , Vascularites associées aux anticorps anti-cytoplasme des neutrophiles/diagnostic , Anticorps anti-cytoplasme des polynucléaires neutrophiles/analyse , Chine/épidémiologie , Défaillance rénale chronique/complications , Lymphocytes , Myeloperoxidase , Études rétrospectivesRésumé
Stroke is the most common disease of the central nervous system, with high disability and mortality, which seriously affects the quality of life of patients and causes a huge disease burden. However, the overall treatment effect is still unsatisfied at present. Myeloperoxidase (MPO), a kind of peroxidase derived from neutrophils, may play an important role in stroke development through many ways, and has great potential in early diagnosis, clinical treatment and prognosis evaluation of stroke. This article reviews the research progress of MPO in stroke, aiming to provide new ideas for better diagnosis and treatment of stroke in clinic.
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To study the clinical features of myeloperoxidase(MPO) antineutrophil cytoplasmic antibody (ANCA) associated hypertrophic pachymeningitis (HP). Clinical data of 15 cases diagnosed with MPO-ANCA vasculitis complicated with HP were retrospectively analyzed. Nine cases were males and the other 6 were females, with an average age of (58±8) years. All cases presented with chronic headache. Contrast-enhanced magnetic resonance imaging (MRI) scan showed local or diffused thickening of cerebral and/or spinal dura matter while brain parenchyma were normal. Nine cases developed multiple cranial nerve paralysis, with trigeminal nerve and auditory nerve involved most commonly. The main clinical manifestations were facial pain, hearing loss and tinnitus. Two cases were complicated with hypertrophic spinal pachymeningitis (HSP) and 4 cases were complicated with pulmonary diseases. Positive serum perinuclear pattern ANCA (pANCA) and MPO could be found in all cases, positive serum IgG 4 was seen in two patients. erythrocyte sedimentation rate(ESR;25-116 mm/1h) and C-reactive protein (CRP;29.02-146.00 mg/L) were both elevated in 14 cases. Nine cases had elevated intracranial pressure[180-235 mmH 2O (1 mmH 2O=0.009 8 kPa)] and abnormal protein level (457.6-3710.0 mg/L) in cerebrospinal fluid. Six cases were treated with glucocorticoids (prednisone 20-60 mg/d) and 9 cased with glucocorticoids and immunosuppressants (methotrexate 15 mg/week or cyclophosphamide 100 mg/d po). All patients achieved remission. MPO-ANCA associated HP is a special type of central nervous system involvement in ANCA associated vasculitis (AAV). It rarely involves the lung or kidney. Steroids and immunosuppressive agents are effective. In HP with unknown underlying diseases, it is suggested to screen ANCA and IgG 4 tests for AAV or IgG 4-related disease.
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Harmaline and harmine are β-carboline alkaloids with effective pharmacological effects. Harmaline can be transformed into harmine after oral administration. However, enzymes involved in the metabolic pathway remain unclear. In this study, harmaline was incubated with rat liver microsomes (RLM), rat brain microsomes (RBM), blood, plasma, broken blood cells, and heme peroxidases including horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO). The production of harmine was determined by a validated UPLC-ESI-MS/MS method. Results showed that heme peroxidases catalyzed the oxidative dehydrogenation of harmaline. All the reactions were in accordance with the Hill equation. The reaction was inhibited by ascorbic acid and excess H2O2. The transformation of harmaline to harmine was confirmed after incubation with blood, plasma, and broken blood cells, rather than RLM and RBM. Harmaline was incubated with blood, plasma, and broken cells liquid for 3 h, and the formation of harmine became stable. Results indicated an integrated metabolic pathway of harmaline, which will lay foundation for the oxidation reaction of dihydro-β-carboline. Moreover, the metabolic stability of harmaline in blood should not be ignored when the pharmacokinetics study of harmaline is carried out.
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Animaux , Rats , Harmaline/métabolisme , Harmine/métabolisme , Hème , Peroxyde d'hydrogène , Spectrométrie de masse en tandemRésumé
Objective:To investigate the expression and clinical significance of neutrophil myeloperoxidase (MPO) in patients with MPO-antibody associated vasculitis (AAV).Methods:Thirty-six newly diagnosed MPO-AAV patients who were hospitalized in the First Affiliated Hospital, Anhui Medical University from July 2018 to June 2021 were enrolled,and 36 age and sex matched healthy subjects were selected as controls. Neutrophil MPO level was detected by flow cytometry (FCM) and MPO mRNA was tested by real time quantitative polymerase chain reaction (RT-qPCR) in all subjects. Serum complement fragment C5 (C5a) and MPO in both groups and serum MPO-anti-antineutrophilic cytoplasmic antibody(ANCA) in MPO-AAV group were measured by enzyme linked immunosorbent assay (ELISA), while the disease activity was evaluated by Birmingham vasculitis activity score-V3 (BVAS-V3).Results:Compared with the heathy control group, the expression of MPO mRNA in neutrophils, serum MPO and complement C5a in MPO-AAV group were significantly higher[MPO mRNA:30.2±11.5 vs. 1.9±0.6, P<0.001;MPO:(112.0±68.7) IU/L vs. (87.4±22.9) IU/L, P=0.01; C5a:(187.3±90.3) ng/ml vs. (107.3±31.1) ng/ml, P<0.001; respectively], while the mean fluorescence intensity (MFI) of MPO in neutrophils were significantly lower [ 1 343.3±723.4 vs. 2 868.0±1 136.5, P<0.001]. In MPO-AAV group, the expression of neutrophil MPO mRNA was positively correlated with serum MPO-ANCA and MPO levels ( r=0.537, P=0.001 and r=0.358, P=0.032; respectively). Multiple regression analysis suggested that neutrophil MPO mRNA expression was positively correlated with serum MPO-ANCA level ( β=0.695, P=0.006); neutrophil MPO level was negatively correlated with serum MPO-ANCA, MPO and complement C5a levels ( r=-0.335, P=0.046; r=-0.372, P=0.026; r=-0.577, P<0.001; respectively). Further, neutrophil MPO level was negatively correlated with serum complement C5a level ( β=-0.374, P=0.043). BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils, serum MPO-ANCA, MPO and complement C5a ( r=0.598, P<0.001; r=0.599, P<0.001; r=0.537, P=0.001; r=0.415, P=0.012; respectively) and negatively correlated with MPO level in neutrophils ( r=-0.342, P=0.041). In multiple regression analysis it suggested that BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils ( β=0.511, P=0.002). Conclusion:In MPO-AAV patients, MPO synthesis and release in neutrophils are both significantly increased, which might be influenced by serum MPO-ANCA and C5a, respectively. Furthermore, MPO synthesis activity in neutrophils is an independent factor related to disease activity.
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Objective: Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality.Methods:The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality. Results:A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95%CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95%CI 0.591 to 1.976, P=0.801).Conclusion: PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.
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Abstract The purpose of this study is to evaluate the preventive effects of Urtica dioica (UD) on muscle ischemia/reperfusion (I/R) injury. A total of 27 male Wistar rats were divided into three groups as the control group (1), I/R + saline group (2), and I/R+UD group (3). Group 1 did not receive any treatment. Group 2 was administered a total of 2mL/kg saline (1mL/kg before ischemia and 1 mL/kg after reperfusion), and group 3 was given a total of 2mL of UD (1mL/kg before ischemia and 1mL/kg after reperfusion) as treatment. Saline and UD were administered via intraesophageal canula once a day for five days. At the end of five days, all the rats were exposed to muscle ischemia for 60 min followed by 60 min of reperfusion of the bilateral hindlimbs induced using a tourniquet. Muscle tissue histopathologies were evaluated by light microscopy. Furthermore, oxidative/nitrosative stress biomarkers such as catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), nitrotyrosine (3-NT), nitric oxide (NO), and myeloperoxidase (MPO) as an inflammatory marker in tissue samples were measured. UD treatment significantly decreased oxidative/nitrosative stress biomarker levels and MPO (p<0.05). We established that UD treatment could alleviate muscle injury induced by muscle I/R in rats by inhibiting the inflammation and oxidative/nitrosative stress
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Animaux , Mâle , Rats , Graines/classification , Myeloperoxidase/analyse , Stress oxydatif , Urtica dioica/effets indésirables , Lésion d'ischémie-reperfusion/anatomopathologieRésumé
Colorectal cancer is one of the most common malignant tumors. Myeloperoxidase (MPO), as an oxidase in neutrophils lysosomes, plays an important role in activating carcinogenic gene intermediates and enhancing exogenous carcinogenesis. It can stimulate oxidative stress reaction in vivo by producing hypochlorite, reactive oxygen species and other oxidants, and induce gene instability factors such as DNA damage, mutation, mismatch repair and so on, which leads to the occurrence and development of colorectal cancer. MPO single nucleotide polymorphism (SNP) is related to the genetic susceptibility of cancer. Mpors 2333227-463G>A can reduce the risk of colorectal cancer. Therefore, the research on MPO, MPO-463G>A will provide new ideas and strong evidence for early detection, prevention, disease assessment and targeted treatment of colorectal cancer.
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Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis is an autoimmune disease usually with severe multiple dysfunction syndrome, especially prominent acute renal failure. A 65-year-old woman was admitted with progressive dyspnoea for six months and fever, sputum with blood, pain of the lower extremities and intermittent claudication for two days, indicating multiple organ involvement (respiratory system, blood vessels). The renal involvement was relatively mild, presenting with microscopic haematuria. The chest computed tomography demonstrated multiple pulmonary embolisms. Ultrasound and computed tomography angiography for the lower extremity vessels showed venous and arterial thrombosis. Exclusion of other diseases that can cause multiple organ damage and thrombosis, the positive perinuclear ANCA and MPO-ANCA strongly support the diagnosis of MPO-ANAC-associated vasculitis. The patient's physical condition has been greatly improved by treatment with corticosteroids and anticoagulation.
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Sujet âgé , Femelle , Humains , Vascularites associées aux anticorps anti-cytoplasme des neutrophiles/diagnostic , Membre inférieur/imagerie diagnostique , Myeloperoxidase , Embolie pulmonaire/imagerie diagnostique , ThromboseRésumé
This study was aimed at investigating the nutrient and bioactive components of Annona muricataand Fagara zanthxoyloidefrom south-southern Nigeria. The roots and leaves of these plants were collected from communities within this region and an analysis of the phytochemical, mineral and vitamin components of these plant parts were carried out using standard methods. The results of the investigation revealed the a high presence of alkaloids (27.34 ± 0.15 and 12.98 ± 0.98), flavonoids (19.66 ± 0.04 and 3.71 ± 0.46) and phenols (15.10 ± 0.11 and 0.07 ± 0.42) in the leaves and roots of Annona muricatawhile alkaloids (35.55 ± 0.95 and 50.90 ± 0.83), tannins (28.70 ± 0.19 and 55.37 ± 0.47) and terpenoids (18.23 ± 0.08 and 41.21 ± 0.16) were observed in leaves and roots of Fagara zanthoxyloide. Mineral analysis revealed the presence of iron (20.23 ± 0.01 and 5.21 ± 0.02), calcium (3.67 ± 0.06 and 1.59 ± 0.01), copper (2.17 ± 0.011 and 0.16 ± 0.01) and magnesium (3.04 ± 0.01 and 2.18 ± 0.005) in leaves and roots of Annona muricataand iron, copper (2.53 ± 0.011and 7.38 ± 0.017) and zinc (5.16 ± 0.02 and 5.32 ± 0.011) in leaves and roots of Fagara zanthoxyloide.The leaves and roots of both plants also showed the presence of folate (26.82±0.48 and 23.47±0.03 for A. muricata and 15.82±0.18 and 20.63±0.91 for F. zanthoxyloide) and ascorbate (31.97±0.03and 26.89±0.19 for A. muricataand13.86±0.13 and 30.21±0.01for F. zanthoxyloide) in appreciable quantities while vitamins D, E and K were also observed in minute concentrations in both plant samples. These results may thus suggest that these plants from this region as a result of their rich nutrients and bioactive compositions may play a large role in alleviating the salient nutritional, physiological and medical challenges observed among people within this region.
Résumé
Objective: To evaluate the immunosuppressive effect on human phagocytes and antibacterial activity of dihydromorin and norartocarpetin isolated from Artocarpus heterophyllus heartwoods. Methods: Dihydromorin and norartocarpetin were isolated from Artocarpus heterophyllus heartwoods. A modified Boyden chamber was used to determine the chemotactic activity of human phagocyte. The respiratory burst was evaluated by chemiluminescence assay. Myeloperoxidase (MPO) activity was quantified using a colorimetric assay. The broth microdilution method was performed to assess their antibacterial activity.Results: Dihydromorin exhibited potent inhibitory effect on the chemotactic activity of polymorphonuclear neutrophils (PMNs) with an IC50 value of 5.03 μg/mL. Dihydromorin also inhibited reactive oxygen species production of whole blood cells, PMNs, and monocytes with IC50 values of 7.88, 7.59 and 7.24 μg/mL, respectively. Interestingly, dihydromorin also strongly inhibited the MPO activity of PMNs with an IC50 value of 5.24 μg/mL, which was lower than indomethacin (24.6 μg/mL). Molecular docking of dihydromorin and crystal structure of MPO showed that dihydromorin had close interaction with key amino acid residues such as Arg239 and Gln91. Antibacterial activity assay showed that only dihydromorin had a strong effect against Streptococcus pyogenes with MIC and MBC values of 15.62 and 31.25 μg/mL, respectively. Conclusions: The results suggest that dihydromorin could be developed as an anti-inflammatory and antibacterial agent.
Résumé
Objective: To evaluate the immunosuppressive effect on human phagocytes and antibacterial activity of dihydromorin and norartocarpetin isolated from Artocarpus heterophyllus heartwoods. Methods: Dihydromorin and norartocarpetin were isolated from Artocarpus heterophyllus heartwoods. A modified Boyden chamber was used to determine the chemotactic activity of human phagocyte. The respiratory burst was evaluated by chemiluminescence assay. Myeloperoxidase (MPO) activity was quantified using a colorimetric assay. The broth microdilution method was performed to assess their antibacterial activity. Results: Dihydromorin exhibited potent inhibitory effect on the chemotactic activity of polymorphonuclear neutrophils (PMNs) with an IC50 value of 5.03 μg/mL. Dihydromorin also inhibited reactive oxygen species production of whole blood cells, PMNs, and monocytes with IC50 values of 7.88, 7.59 and 7.24 μg/mL, respectively. Interestingly, dihydromorin also strongly inhibited the MPO activity of PMNs with an IC50 value of 5.24 μg/mL, which was lower than indomethacin (24.6 μg/mL). Molecular docking of dihydromorin and crystal structure of MPO showed that dihydromorin had close interaction with key amino acid residues such as Arg239 and Gln91. Antibacterial activity assay showed that only dihydromorin had a strong effect against Streptococcus pyogenes with MIC and MBC values of 15.62 and 31.25 μg/mL, respectively. Conclusions: The results suggest that dihydromorin could be developed as an anti-inflammatory and antibacterial agent.