Serum Myeloperoxidase Research Articles

Nisin Z attenuates lipopolysaccharide-induced mastitis by inhibiting the ERK1/2 and p38 mitogen-activated protein kinase signaling pathways

Nisin Z is a possible alternative for treating bovine mastitis by inhibiting mastitis-causing pathogens and having anti-inflammatory activity. However, the anti-inflammatory mechanism of nisin Z on mastitis is unknown. Our study aimed to investigate the mechanisms of nisin Z on mastitis. Our results showed that nisin Z inhibited the activation of the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) signaling pathway, decreased the release of pro-inflammatory cytokines (i.e., tumor necrosis factor-α, IL-1β, and IL-6), and increased the anti-inflammatory cytokine (IL-10) in lipopolysaccharide (LPS)-induced MCF10A cells. After intraperitoneal injection, nisin Z significantly decreased inflammatory cell infiltration in the mammary gland, as well as decreased myeloperoxidase and pro-inflammatory cytokines in serum and mammary gland. Western blot analysis revealed that nisin Z also dramatically suppressed the activation of the ERK1/2 and p38 MAPK signaling pathways in LPS-induced mastitis mice. We also found that nisin Z treatment could enhance the blood-milk barrier. In summary, our study demonstrated that nisin Z exerted an anti-inflammatory effect by inhibiting the ERK1/2 and p38 MAPK signaling pathway and promoting the blood-milk barrier on LPS-induced mastitis.

Prognostic indicators for the onset of ischaemic versus haemorrhagic stroke in stable coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: None. Background The incidence of stroke may be increased in patients with coronary artery disease (CAD). We aimed to investigate the specific risk factors for the development of ischaemic and haemorrhagic stroke in stable CAD patients. Methods Patients with stable CAD were prospectively enrolled for future cardiovascular events in Taiwan. All the patients had received coronary interventions and were stable for least 1 month before enrolment. The incidence of ischaemic stroke was identified and confirmed by telephone and hospital records. Baseline characteristics, including demographic data, lipid profiles, medications, and biomarkers for potential inflammatory and atherosclerosis, were analysed. Results In total, 1428 patients (age, 63.07 ± 11.4 years; 1207 males) were under standard medical treatment and regularly followed-up for at least 4 years. Multivariate logistic regression analysis showed that baseline serum myeloperoxidase (MPO) level (HR: 1.89, 95% CI: 1.16-3.10, p = 0.01) and statin use (HR: 0.37; 95% CI: 0.17-0.79, p = 0.01) were independently associated with the onset of ischaemic stroke. Age (HR: 1.07, 95% CI: 1.00-1.14, p = 0.04) and angiotensin receptor blocker (ARB) use (HR: 0.37, 95% CI: 0.17-0.79, p = 0.01) were independently associated with future onset of intracranial haemorrhage (ICH), implying the different mechanisms of ischaemic stroke and ICH. Conclusion Age and ARB use were related to ICH onset. Baseline MPO level and statin use were independently associated with longer and shorter future ischaemic stroke onset in stable CAD patients, respectively. Further studies are indicated to confirm the potential mechanisms and advance individual risk stratification for the onset of different types of stroke in clinical CAD.

The Impact of the Animal Housing System on Immune Cell Composition and Function in the Blood of Dromedary Camels

Simple SummaryThe present study investigated the impacts of a change in animal housing system on selected parameters of the camel immune system. Samples collected from camels during a free-ranging time were compared with samples collected from the same camels during movement-restricted housing. Movement-restricted camels showed elevated myeloperoxidase activity in their serum, a significant shape-change of their neutrophils, and higher reactive oxygen species content in their monocytes and neutrophils. The leukogram pattern of the camels under restricted housing was characterized by increased numbers of neutrophils, eosinophils, lymphocytes, and monocytes. Within the lymphocyte population, only the helper T cells and B cells were expanded in animals under restricted housing. In addition, restricted housing modulated the expression of several cell surface antigens, including monocyte-polarization markers and cell adhesion molecules. Functional analysis of bacterial phagocytosis indicated impaired antibacterial function of phagocytes in camels under restricted housing. In summary, the present study identified significant changes in blood immune cell composition, phenotype, and function in dromedary camels under restricted-housing conditions, and suggests the development of an excitement leukogram in those animals.Background: The dromedary camel (Camelus dromedarius) is an important livestock animal of desert and semi-desert ecosystems. In recent years, several elements of the camel immune system have been characterized. Stress and excitement induced by animal housing represent the most important environmental factors with potential modulatory effects on the immune system. The present study evaluated the impacts of a restricted-housing system on some phenotypic and functional properties of blood leukocytes in dromedary camels. Methods: Immunofluorescence and flow cytometry were used to comparatively analyze samples collected from camels during a free-ranging time and samples collected from the same camels during movement-restricted housing. Results: In comparison to blood samples collected from the camels during the free-ranging time, samples from movement-restricted camels showed elevated serum myeloperoxidase activity, a significant shape-change in their neutrophils, and higher reactive oxygen species content in their monocytes and neutrophils, indicating increased cellular oxidative stress under movement-restricted housing. The leukogram pattern of the camels under restricted housing was characterized by leukocytosis with increased numbers of neutrophils, eosinophils, lymphocytes, and monocytes, resembling an excitement leukogram pattern. Within the lymphocyte population, only the helper T cells and B cells were expanded in animals under restricted housing. The upregulation of CD163 together with the downregulation of MHC-II on monocytes from excited camels indicate a modulatory potential of animal excitement to polarize monocytes toward an anti-inflammatory phenotype. Functional analysis of bacterial phagocytosis indicates an impaired antibacterial function of phagocytes in excited camels. The downregulation of several cell adhesion molecules on leukocytes from excited camels suggests a role for impaired cell adhesion and tissue migration and leukocyte retention in blood in the observed leukocytosis in animals under excitement. Conclusions: The present study identified significant changes in blood immune cell composition, phenotype, and function in dromedary camels under restricted-housing conditions. The observed changes in leukocyte composition suggest the development of an excitement leukogram pattern in camels under movement-restricted housing. To evaluate the clinical relevance of the observed changes in immune cell phenotype and function for the immune competence of camels under restricted housing, further studies are required.

Modulation of expression of proinflammatory genes and humoral immune response following immunization or infection with Aeromonas hydrophila in silver catfish (Rhamdia quelen)

The early immune-related events arising from the interaction of antigen and innate immune cells are central to modulating the acquired immune response. Ideally, the immunizing antigen should elicit immunological changes similar to that observed after infection with the wild type pathogen. Here, we evaluated early changes on the expression of selected proinflammatory genes (TNF-α, IL-1β, IRAK4 and myeloperoxidase) and innate immune parameters (serum myeloperoxidase, lysozyme and complement hemolytic activity) in silver catfish vaccinated or infected with Aeromonas hydrophila, the etiological agent of hemorrhagic septicemia. The humoral immune response and resistance to challenge were also evaluated in vaccinated and placebo inoculated fish. We found that the expression of TNF-α and IL-1β genes was higher (p<0.05) in vaccinated or infected fish at 24 h post inoculation (p.i) compared to the control group but returned to basal levels at 72 h p.i. The expression of IRAK4 gene, however, was not altered by vaccination or infection. In addition, the natural hemolytic activity of complement was higher (p<0.05) at 24 h and 72 h p.i. in the vaccinated and infected groups; serum myeloperoxidase was higher (p<0.05) in these groups but only at 24 h p.i. and lysozyme activity was higher (p<0.05) only in the infected group at 72 h p.i. Furthermore, vaccination induced the production of IgM-like antibodies and protection to challenge with the A. hydrophila. Our results indicate that the vaccine formulation induces an immune response similar to that induced by the infecting pathogen and might be a valuable tool in the prophylaxis of hemorrhagic septicemia in silver catfish.

Changes in immune genes expression, immune response, digestive enzymes -antioxidant status, and growth of catla (Catla catla) fed with Astragalus polysaccharides against edwardsiellosis disease

The effect of four level of Astragalus polysaccharides (APs) supplementation diets, (CD: control diet and three experiment diet (E), EA: 100 mg kg−1 APs; EB: 200 mg kg-1 APs; EC: 300 mg kg−1 APs) on growth, changes in haemato-biochemical parameters and metabolic-digestive enzymes, enhancement of antioxidant activity, innate-adaptive immune response, and cytokine gene expression were studied in catla (Catla catla) against Edwardsiella tarda. The healthy and challenged groups fed the CD displayed no mortality, while fish fed EA or EC revealed 10% mortality, but the mortality was only 5% in diet EB. Fish fed diet EB and EC revealed significantly better growth rates and high RBC count during the experimental period. Albumin and globulin levels were significant improved when fish were fed the diet EB and EC from weeks 6–8. The superoxide dismutase (SOD) was significant ameliorated by EB feeding from weeks 4–8. In contrast, serum myeloperoxidase (MPO), catalase (CAT), malondialdehyde (MDA)/lipid peroxidation (LPO), glutathione peroxidase (GPx), respiratory burst activity (RBA), bactericidal action (BCA), serum lysozyme activity (SLA), nitric oxide synthase (NOS), head kidney leukocytes response proliferation (HKLP), hemolytic action (HLA), hydrogen peroxides (H2O2), and immunoglobulin (Ig) were significantly improved from week 6–8. Groups fed the APs enriched diets had significant ameliorated interleukin (IL)-1β and interferon (IFN)-γ mRNA expression after 6 and 8 weeks of feeding. However, IL-10 and major histocompatibility complex (MHC)-1 mRNA expressions were significant enhanced in catla fed all APs diets on week 8. APs enriched diets revealed significant improved tumor necrosis factor (TNF)-α and TNF receptor-associated factor-6 (TRAF6) mRNA expression on week 4, but toll-like receptor-2 (TLR2) and TLR4 mRNA expression were significant enhanced by diet EB and EC after weeks 6 and 8. Similarly, the lysozyme (Lyz)-C and Lyz-G mRNA levels in the head kidney (HK) increased by APs feeding on weeks 6 and 8, whereas the EB diet, the expression of nucleotide binding oligomerization domain-1 (NOD1) was significantly improved on weeks 6 and 8, but NOD2 mRNA expression was only significant enhanced after 8 weeks of diet EB. By feeding healthy catla and E. tarda challenged fish fed diet EB, resulted in significantly increased growth, haemato-biochemical indices, metabolic-digestive enzymes, antioxidant activities, innate-adaptive immune responses, and cytokine gene expression mainly between 6 and 8 weeks.

Impacts on the immune system of &lt;i&gt;Cyprinus carpio&lt;/i&gt; exposure with a mixed algal extract against &lt;i&gt;Aeromonas hydrophila&lt;/i&gt;

This study evaluates the influence of mixed algal extract (&lt;i&gt;Chlorella vulgaris&lt;/i&gt;, &lt;i&gt;Euglena viridis&lt;/i&gt; and &lt;i&gt;Spirulina platensis&lt;/i&gt;) on common carp &lt;i&gt;Cyprinus Carpio&lt;/i&gt;, which infected infect with bacterial pathogen &lt;i&gt;Aeromonas hydrophila&lt;/i&gt;. &lt;i&gt;C. carpio&lt;/i&gt; was administered intraperitoneally with various doses such as methanol extract (0, 0,1, 1, 10 and 100 mg/kg). The immunological parameters of fish blood and serum samples (Neutrophil activity, Lysozyme activity, Serum myeloperoxidase intensity, Serum bactericidal activity, and Serum antiprotease activity) were investigated at 7, 14, 21, and 28 days of post-immunization. Fish had been tested by virulent&lt;i&gt; A. hydrophila&lt;/i&gt; for 30 days after treatment and 14 days after infection were identified with mortalities. The findings showed that neutrophil levels, lysozyme activity, serum bactericidal activity, myeloperoxidase activity, and serum antiprotease activity significantly enhanced (p&lt;0.05) compared to untreated control. Mixed dietary algae at 1 and 10 mg/kg levels demonstrated slightly (p&lt;0.05) higher relative percentage survival (90 percent) than control against &lt;i&gt;A. hydrophila&lt;/i&gt; disease infection. Results indicated that mixed algal extract in &lt;i&gt;C. carpio&lt;/i&gt; positively impacts non-specific immune parameters and boosts disease tolerance to &lt;i&gt;A. hydrophila&lt;/i&gt; infections.

El aumento de la mieloperoxidasa sérica se correlaciona con datos clínicos de la enfermedad de Parkinson

Objectives. Myeloperoxidase (MPO) has been implicated in Parkinson´s disease (PD). The objective was to look at the relationship of MPO concentration in serum and cerebrospinal fluid (CSF) with clinical variables of PD. Methods. In this prospective, observational, and cross-sectional study, MPO concentration in serum and the CSF was analyzed in 36 patients with idiopathic PD and 30 controls, who were enrolled from 2012 to 2017. In the group of patients, correlation of MPO content with demographic, clinical and tomographic variables was examined. The extent and degree of nigrostriatal dopaminergic cell loss was evaluated by using SPECT and 123I-Ioflupane, radioligand that has binding affinity for dopamine-transporter (DAT). Results. Serum MPO concentration, not CSF MPO content, was significantly higher in the patients (p&lt;.0001). Significant correlation values were found between serum MPO concentration and rating scales of motor severity (Hoehn-Yahr, MDS-UPDRS part-III), and percentage reduction of DAT binding on basal ganglia (p&lt;.0001). Patients with moderate-advanced disease (Hoehn-Yahr stage 3) showed significantly higher serum MPO content relative to patients with early disease (Hoehn-Yahr stages 1-2, p&lt;.0001). DAT binding was reduced on all striatal regions, and signal reduction was higher in the putamen relative to the caudate nucleus (p&lt;.0001). Percentage reduction of DAT binding on the striatum and putamen significantly correlated with rating scales of motor severity. Conclusions. Myeloperoxidase content in serum is increased in PD patients and correlates with motor severity degree and loss of dopamine-transporter binding on basal ganglia. The results allow proposing that the measurement of MPO level in serum could be useful for PD diagnosis, and that the inhibition of serum MPO would be a promising therapeutic tool. The study also confirms that the putamen shows higher reduction of DAT binding than the caudate nucleus, and degree of nigrostriatal dopaminergic cell loss is well quantified with rating scales of motor severity.

Fraction from Calliandra portoricensis reduces 7, 12 dimethylbenz(a)anthracene-induced mammary tumors in Wistar rats.

Objective: Calliandra portoricensis (CP) is used in Nigeria for the treatment of breast diseases. We investigated the effects of fraction from CP on 7, 12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland tumors. Materials and Methods:Female Wistar rats (40) were allotted into five equal groups. Group 1 served as control, group 2 received DMBA (50 mg/kg), groups 3 and 4 received DMBA and were treated with CP at doses of 50 and 100 mg/kg respectively, and the group 5 received DMBA and vincristine (0.5 mg/kg). DMBA was injected intraperitoneally once while vincristine and CP were given twice and thrice per week, respectively. Results:Administration ofDMBA caused a significant decrease in body weight gain by 52%. In addition, DMBA significantly increased organo-somatic weight of mammary gland by 4.0 folds. Also, DMBA significantly increased inflammatory and oxidative stress markers serum interleukin-1β (IL-1β), lipid peroxidation (LPO) and myeloperoxidase (MPO) by 27, 18 and 435%, respectively. Similarly, mammary NO (nitric oxide) and LPO were increased by 468 and 21%, respectively. In contrast, DMBA decreased the levels of apoptotic markers BAX, caspases 3 and 9 by 20, 15 and 18%, and mammary superoxide dismutase (SOD), catalase (CAT) and glutathione-s-peroxidase (GPx) by 45, 51 and 68%, respectively. Histology revealed gland with malignant epithelial cells and high nucleo-cytoplasm in DMBA-administered rats. Treatment with CP 100 mg/kg decreased LPO, MPO, IL-1β and NO by 28, 35, 78 and 85%, respectively, and ameliorated DMBA-induced cyto-architectural anomalies. Conclusion:Fraction of CP protects mammary gland from DMBA insults via antioxidative and anti-inflammatory mechanisms.

Cerebrolysin Amelioration of Spinal Cord Ischemia/ Reperfusion Injury in Rabbit Model.

Cerebrolysin is a well-known neuroprotective agent. This study investigated its effects on inflammation, oxidative stress, apoptosis, and neurologic recovery in the setting of spinal cord ischemia/reperfusion injury (SCIRI) in an experimental animal model. Rabbits were randomly divided into five groups: control, ischemia, vehicle, methylprednisolone (30 mg/kg), and cerebrolysin (5 ml/kg) group. The rabbits in the control group underwent laparotomy; the other groups underwent spinal cord ischemia and reperfusion injury for 20 min. Neurologic examination after 24 h was based on the Modified Tarlov scale. Myeloperoxidase activities, catalase and malondialdehyde levels, and caspase-3 concentrations were determined in serum and tissue samples. Serum xanthine oxidase levels were studied and histopathological and ultrastructural changes were examined. After SCIRI, serum and tissue myeloperoxidase activities, malondialdehyde levels, caspase-3 concentrations, and serum xanthine oxidase activities were increased (p 0.01-0.001). Catalase levels were significantly diminished (p 0.001). Cerebrolysin treatment correlated with reduced myeloperoxidase and xanthine oxidase activities, malondialdehyde levels and caspase-3 concentrations; and with increased catalase levels (p 0.001, for all). The cerebrolysin group showed improved histopathological, ultrastructural, and neurological outcomes. For the first time in the literature the current study reports anti-inflammatory, antioxidant, antiapoptotic, and neuroprotective effects of cerebrolysin in a SCIRI rabbit model.

Enhancement of growth, antioxidative status, nonspecific immunity, and disease resistance in gibel carp (Carassius auratus) in response to dietary Flos populi extract

This study investigated the effects of dietary Flos populi extract (FPE) on the growth, antioxidation capability, innate immune response, and disease resistance in gibel carp. A total of 480 fish were fed with five different diets containing 0, 0.5, 1.0, 1.5, or 2.0 g kg−1 FPE (designated as control, D0.5, D1.0, D1.5, or D2.0 groups) for 45 days. The fish were challenged with A. hydrophila after the feeding trial. Compared with the control, the feed efficiency (FE), weight gain (WG), final body weight (FBW), and specific growth rate (SGR) were significantly improved in groups D1.0 and D1.5. Dietary FPE significantly increased serum superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities, as well as glutathione (GSH) content. The contents of protein carbonyl (PCC) and malondialdehyde (MDA) in serum decreased significantly. Additionally, FPE supplementation in diets resulted in significant improvement in serum lysozyme (LZM) and myeloperoxidase (MPO) activities, as well as immunoglobulin M (IgM) and complement 3 (C3) concentrations. The hepatic antioxidant enzymes (CAT and SOD) activities increased, whereas content of MDA decreased in fish treated with dietary FPE than those of control both pre- and post-challenged. After 12 h-challenge, an obvious downregulation of hepatic Kelch-like-ECH-associated protein 1 (Keap1), splenic tumor necrosis factor-α (TNF-α), interleukin (IL)-8, IL-1β, and toll-like receptor 2 (TLR2) mRNA levels was observed in fish treated with dietary FPE, whereas hepatic Nrf2 transcription level was upregulated compared to the control. Furthermore, compared to group D0.5, higher relative percent survival (RPS) was observed in gibel carp fed dietary 1.0–2.0 g/kg FPE. Our results reveal that FPE supplemented diet has a stimulatory effect on antioxidant capacity and nonspecific immune response, along with improved growth performance and enhanced resistance against A. hydrophila infection in juvenile gibel carp.

Rectal roflumilast improves trinitrobenzenesulfonic acid-induced chronic colitis in rats.

Roflumilast, a highly selective oral phosphodiesterase IV inhibitor, exerts anti-inflammatory and anti-fibrotic effects. Oral roflumilast causes gastrointestinal side effects, especially vomiting, which could be reduced by administering roflumilast via off-label routes. Inhaled roflumilast reportedly improved inflammatory and histopathological changes in asthmatic mice. The current study investigated the effects of oral and rectal roflumilast on trinitrobenzenesulfonic acid (TNBS)-induced chronic colitis in rats, an experimental model resembling human Crohn's disease. Five groups of rats (n=8) were used: normal control, TNBS-induced colitis, and three TNBS-treated colitic groups, which received oral sulfasalazine (500 mg·kg-1·day-1), oral roflumilast (5 mg·kg-1·day-1), or rectal roflumilast (5 mg·kg-1·day-1) for 15 days after colitis induction. Then, the following were assessed: the colitis activity score, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and IL-6 serum levels, colonic length, and myeloperoxidase, malonaldehyde, and glutathione levels. Histological examinations employed H&E, Masson trichrome, and PAS stains in addition to immunostaining for KI-67 and TNF-α. The TNBS-induced colitis rats showed significant increases in disease activity scores, serum TNF-α, IL-2, and IL-6 levels, and colonic myeloperoxidase and malonaldehyde content. They also showed significant decreases in colonic length and glutathione levels in addition to histopathological and immunohistochemical changes. All the treatments significantly improved all these changes. Sulfasalazine provided the greatest improvement, followed by oral roflumilast, and then rectal roflumilast. In conclusion, both oral and rectal roflumilast partially improved TNBS-induced chronic colitis, suggesting the potential of roflumilast as an additional treatment for Crohn's disease.

Protective effects of pre-treatment with exogenous porcine glucagon-like peptide-2 and its microspheres of piglets with lipopolysaccharide-induced intestinal inflammation

Context Glucagon-like peptide-2 (GLP-2) is an intestinotrophic growth hormone that can accelerate intestinal development and recovery from injury. However, the half-life of GLP-2 is short, thus it must be administered frequently. Moreover, its effects during weaning are unclear. Aims We tested the effects of porcine GLP-2 (pGLP-2) and pGLP-2 microspheres on lipopolysaccharide (LPS)-induced intestinal inflammation in weaning piglets. Methods Eighteen female weaning piglets aged 21 days (5.38 ± 0.72 kg initial bodyweight) were randomly assigned to three treatment groups: (1) control, (2) GLP-2, and (3) GLP-2 microsphere (MS) group. Control piglets were injected intraperitoneally with 3 mL of saline solution from Days 1 to 7, GLP-2 piglets were injected intraperitoneally with 100 μg pGLP-2/kg bodyweight from Days 1 to 7, and MS piglets were injected intraperitoneally with 200 mg GLP-2 microspheres on Day 1 and with 3 mL saline solution from Days 2 to 7. On Day 8, all piglets were injected with 100 μg LPS/kg bodyweight. Key results Piglets in the GLP-2 and MS groups showed markedly increased average daily weight gain on Day 7, decreased serum myeloperoxidase, LPS and keratinocyte growth factor levels, and increased serum interleukin-10 levels compared with the control group. In addition, the GLP-2 group showed decreased myeloperoxidase content in the duodenum and ileum, and reduced caspase-3 activity in the duodenum and jejunum, whereas MS piglets showed decreased myeloperoxidase levels and suppressed caspase-3 activity in the duodenum and jejunum. Moreover, administration of pGLP-2 or pGLP-2 microspheres resulted in decreased interleukin-8 and interferon-γ mRNA expression levels in the jejunum, as compared with the control group. Conclusions Our results indicated that pGLP-2 promotes growth, and ameliorates LPS-induced serum and intestinal inflammatory responses in piglets. Furthermore, pGLP-2 microspheres can achieve similar therapeutic effects as pGLP-2 under the premise of fewer injections. Implications pGLP-2 microspheres have considerable potential for the treatment of weaning-induced intestinal inflammation in piglets.

Orchid Dendrobium alpestre Royle enhances survival in lethal sepsis induced in mice

Despite advances in medical care and therapy, sepsis is still one of the major causes of death in intensive care units, and no decisive medical treatment is available against sepsis. The present study investigated the antibacterial activity, acute toxicity studies, hemodynamic parameters, myeloperoxidase (MPO) activity of hydroalcoholic extract of Dendrobium alpestre (Da), and its effects on cecal ligation and puncture (CLP) induced sepsis in mice. At equivalent concentration, Da showed antibacterial activities as potent as streptomycin against Staphylococcus aureus and Escherichia coli. Acute toxicity studies on mice found out that Da was non-toxic up to 2000 mg/Kg body weight, and the low and high dose was fixed as 100 and 200 mg/Kg body weight, respectively. At both doses, Da improved hemodynamic parameters such as mean arterial pressure and decreased optical density of blood, while it decreased serum MPO activity. Moreover, at a high dose, Da reduced the survival rate to 92.50±3.50% in mice that might be through pro-inflammatory effects. The results indicate that D. alpestre can be a favourable natural source for the treatment of CLP-induced sepsis in mice.

Prognostic indicators for the onset of ischaemic versus haemorrhagic stroke in stable coronary artery disease.

The incidence of stroke may be increased in patients with coronary artery disease (CAD). We aimed to investigate the specific risk factors for the development of ischaemic and haemorrhagic stroke in stable CAD patients.Patients with stable CAD were prospectively enrolled for future cardiovascular events in Taiwan. All the patients had received coronary interventions and were stable for least 1 month before enrolment. The incidence of ischaemic stroke was identified and confirmed by telephone and hospital records. Baseline characteristics, including demographic data, lipid profiles, medications, and biomarkers for potential inflammatory and atherosclerosis, were analysed.In total, 1428 patients (age, 63.07 ± 11.4 years; 1207 males) were under standard medical treatment and regularly followed-up for at least 4 years. Multivariate logistic regression analysis showed that baseline serum myeloperoxidase (MPO) level (hazard ratio [HR]: 1.89, 95% CI: 1.16–3.10, P = .01) and statin use (HR: 0.37; 95% CI: 0.17–0.79, P = .01) were independently associated with the onset of ischaemic stroke. Age (HR: 1.07, 95% CI: 1.00–1.14, P = .04) and angiotensin receptor blocker (ARB) use (HR: 0.37, 95% CI: 0.17–0.79, P = .01) were independently associated with future onset of intracranial haemorrhage (ICH), implying the different mechanisms of ischaemic stroke and ICH.Age and ARB use were related to ICH onset. Baseline MPO level and statin use were independently associated with longer and shorter future ischaemic stroke onset in stable CAD patients, respectively. Further studies are indicated to confirm the potential mechanisms and advance individual risk stratification for the onset of different types of stroke in clinical CAD.

P-coumaric acid ameliorates fipronil induced liver injury in mice through attenuation of structural changes, oxidative stress and inflammation

Fipronil is a broad-spectrum phenylpyrazole insecticide and has been used effectively in the agriculture. Due to its widespread use and bioaccumulation in the environment, it possesses significant threat to human and animals. P-coumaric acid is a natural dietary polyphenolic compound that has anti-oxidant and anti-inflammatory property. The present study was aim to investigate the ameliorative effect of p-coumaric acid on fipronil induced liver injury. The mice were divided into five groups (SHAM, FPN, FPN/PCA/50, FPN/PCA/100 and PCA/100) and challenged with fipronil @ 25 mg/kg bw (half of LD50). Haematological, liver function biomarkers (ALT, AST, ALP, GGT), biochemical parameters (MPO, oxidative, nitrosative stress and anti-oxidant enzyme activity), levels of serum and liver inflammatory cytokines (TNF-α, IL-1β and IL-10), histopathology were monitored. Fipronil administration caused a significant increase in liver enzymes with concomitant significant increase in inflammatory cytokines (TNF-α, IL-1β, IL-10) and myeloperoxidase activity. A significant increase in oxidative stress (lipid peroxidation, nitric oxide) as well as down regulation of anti-oxidant enzymes like superoxide dismutase (SOD) and catalase (CAT) along with histopathological changes such as microsteatosis, hypertrophy of the hepatocytes and necrosis were observed on fipronil administration. Administration of p-coumaric acid against fipronil caused decreased serum liver enzymes, inflammatory cytokines, myeloperoxidase activity and oxidative stress along with improvement in anti-oxidant enzyme levels and structural changes induced by fipronil. Thus p-coumaric acid ameliorates the FPN induced liver injury in mice through attenuation of structural changes, oxidative stress, and inflammation.

LPS-induced macrophage HMGB1-loaded extracellular vesicles trigger hepatocyte pyroptosis by activating the NLRP3 inflammasome

Extracellular vesicles (EVs) have emerged as important vectors of intercellular dialogue. High mobility group box protein 1 (HMGB1) is a typical damage-associated molecular pattern (DAMP) molecule, which is cytotoxic and leads to cell death and tissue injury. Whether EVs are involved in the release of HMGB1 in lipopolysaccharide (LPS)-induced acute liver injuries need more investigation. EVs were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blotting. The co-localization of HMGB1, RAGE (receptor for advanced glycation end-products), EEA1, Rab5, Rab7, Lamp1 and transferrin were detected by confocal microscopy. The interaction of HMGB1 and RAGE were investigated by co-immunoprecipitation. EVs were labeled with the PKH67 and used for uptake experiments. The pyroptotic cell death was determined by FLICA 660-YVAD-FMK. The expression of NLRP3 (NOD-like receptor family pyrin domain containing 3) inflammasomes were analyzed by western-blot or immunohistochemistry. Serum HMGB1, ALT (alanine aminotransferase), AST (aspartate aminotransferase), LDH (lactate dehydrogenase) and MPO (myeloperoxidase) were measured using a commercial kit. The extracellular vesicle HMGB1 was detected in the serums of sepsis patients. Macrophages were found to contribute to HMGB1 release through the EVs. HMGB1-RAGE interactions participated in the loading of HMGB1 into the EVs. These EVs shuttled HMGB1 to target cells by transferrin-mediated endocytosis leading to hepatocyte pyroptosis by the activation of NLRP3 inflammasomes. Moreover, a positive correlation was verified between the sepsis serum EVs-HMGB1 level and clinical liver damage. This finding provides insights for the development of novel diagnostic and therapeutic strategies for acute liver injuries.

Critical water quality parameters and certain non specific immune parameters of Clarias gariepinus juveniles raised in bioflocs system with cassava flour and rice bran as carbon sources

This study was conducted to examine effects of bioflocs culture on critical water parameters and certain non specific immune parameters in C. gariepinus juveniles. This experiment was conducted for 72 days, in 9 separate tanks with an aerated blower. Bioflocs culture had two different sources of carbon addition. This research consists of three treatments, carbon sources were added at CN ratio of 15:1. Results showed no significant difference in dissolved oxygen, pH, and temperature in all treatments. However, conductivity, Total dissolved solids and salinity showed significant difference across all treatment groups. Total ammonia nitrogen, nitrate and nitrite showed significant difference between control and bioflocs treatments. Blood parameters examined were serum lysozyme, myeloperoxidase activity, neutrophils, lymphocytes and monocytes percentage. Serum lysozyme and myeloperoxidase showed significant difference across treatments while neutrophils percentage showed significant difference between bioflocs culture and control experiment. Lymphocytes and monocytes showed no significant difference.

Cross-Talk Between Nitrosative Stress, Inflammation and Hypoxia-Inducible Factor in Patients with Adrenal Masses.

BackgroundAdrenal masses are the most common of all human tumors. The role of nitrosative stress and inflammation in cancer development has already been demonstrated. However, it is not known whether they are involved in the pathogenesis of adrenal tumors. The aim of the study was to investigate a cross-talk between nitrosative stress, inflammation and hypoxia-inducible factor (HIF-1α) in 75 patients with different types of adrenal masses (non-functional incidentaloma, pheochromocytoma and Cushing’s/Conn’s adenoma).MethodsThe plasma concentrations of total nitric oxide (NO), S-nitrosothiols, peroxynitrite nitrotyrosine and the activity of serum myeloperoxidase (MPO) were measured spectrophotometrically, whereas concentrations of interleukin 1 beta (IL-1β), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1 alpha (HIF-1α) were measured using commercial ELISA kits. The control group consisted of 50 healthy people matched by age and sex to the study group. The number of subjects was determined a priori based on our previous experiment (power of the test = 0.9; α = 0.05).ResultsWe found significantly higher nitrosative stress (↑nitric oxide, ↑peroxynitrite, ↑S-nitrosothiols and ↑nitrotyrosine) in the plasma of patients with adrenal tumors, which was accompanied by increased inflammatory (↑myeloperoxidase, ↑interleukin 1 beta and ↑tumor necrosis factor α) and hypoxia (HIF-1α) biomarkers. Peroxynitrite and nitrotyrosine were positively correlated with aldosterone level. Nitrosative stress was also associated with inflammation and HIF-1α. Interestingly, plasma nitrotyrosine and serum MPO differentiated patients with adrenal tumor from healthy individuals with high sensitivity and specificity. Moreover, using multivariate regression analysis, we showed that ONOO− and IL-1β depended on cortisol level, while ONOO−, nitrotyrosine and HIF-1α were associated with aldosterone. Unfortunately, none of the assessed biomarkers differentiated between tumor types studied, suggesting that the severity of nitrosative damage and inflammation are similar in patients with incidentaloma, pheochromocytoma, and Cushing’s or Conn’s adenoma.ConclusionAdrenal tumors are associated with increased protein nitration/S-nitrosylation and inflammation.

Investigating the Effects of Dapagliflozin on Cardiac Function, Inflammatory Response, and Cardiovascular Outcome in Patients with STEMI Complicated with T2DM after PCI.

Objective To explore the effect of dapagliflozin on cardiac function, inflammation, and cardiovascular outcome in patients with ST-segment elevation myocardial infarction (STEMI) combined with type 2 diabetes (T2DM) after percutaneous coronary intervention (PCI). Methods 70 patients with STEMI and T2DM were divided into the control group (n = 35) and the observation group (n = 35). Before surgery, patients in both groups were given conventional treatments such as coronary expansion, antiplatelet, anticoagulation, and thrombolysis, and PCI was performed. After the operation, both groups were given conventional antiplatelet, anticoagulation, lipid-lowering, and hypoglycemic treatments. On this basis, the observation group was treated with dapagliflozin tablets for 24 weeks. We observe and compare the left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF), myocardial enzyme spectrum, inflammatory reaction, and occurrence of adverse cardiovascular events (MACE) of the two groups of patients before and after treatment. Results After treatment, the LVEDD and LVESD of the two groups were lower than those before treatment, and the observation group was lower than the control group (P < 0.05). The LVEF of both groups was higher than that before treatment, and the observation group was higher than the control group (P < 0.05). After treatment, the levels of two groups' patients' creatine kinase (CK), creatine kinase isoenzyme (CK-MB), and troponin I (cTnI) were all lower than those before treatment, and the observation group patients were all lower than the control group (P < 0.05). After treatment, the levels of serum myeloperoxidase (MPO), C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in the two groups were all lower than those before treatment, and the observation group patients were all lower than the control group (P < 0.05). After treatment, there was no statistical difference between the two groups of patients in cardiogenic death, recurrent myocardial infarction, and other adverse cardiovascular events (P > 0.05). But, the incidence of severe arrhythmia and heart failure in the observation group were both lower than those in the control group (P < 0.05). Kaplan–Meier survival curve analysis showed that the median survival time without MACE in the observation group was higher than that in the control group (P < 0.05). Conclusion Dapagliflozin treatment for patients with STEMI combined with T2DM after PCI can improve cardiac function to certain extent, reduce inflammation, and will reduce the incidence of adverse cardiovascular outcomes.

Effects of Naringenin on ExperimentallyInducedRheumatoid Arthritis in Wistar Rats.

Naringenin is one of the most important and abundant known flavonoids found in grapefruit and other citrus fruits. This experimental study aimed to assess the clinical effects and immune responses of naringenin in the animal model of rheumatoid arthritis (RA) according to various reports on its anti-inflammatory effects and modulation of the immune system. To this end, 40 Wistar rats in the weight range of 160-180g were randomly assigned to four groups (n=10) including healthy, control, naringenin, and methotrexate orally treated groups. To induce RA disease, a compound of 200 μl of Freund's adjuvant and collagen type II was injected subcutaneously into the rear footpads of rats. The severity of RA clinical signs was assessed based on a standard scoring method. The treatment lasted for three weeks (days7-28 after induction). The obtained data pointed out that the levels of C-reactive protein (CRP), myeloperoxidase, nitric oxide, IL-17, and IFN-γ cytokines significantly increased in the RA rats, while the level of their serum antioxidants significantly reduced, compared to the healthy rats. The inflammation of the paws and the level of CRP decreased similarly in both methotrexate and naringenin-treated groups. In the naringenin-treated group, a further decrease was detected in serum myeloperoxidase, nitric oxide, and the total antioxidant capacity occurred, as compared to the methotrexate-treated rats. Nonetheless, IL-17 and IFN-γ cytokines levels were further decreased in the methotrexate-treated group. Accordingly, it can be concluded that naringenin can be effectively used for the reduction of inflammatory effects and control of RA disease.