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Background Several evidences report that a vegetarian diet is protector against cardiovascular diseases. Few studies have demonstrated the circulating profile of cardiovascular biomarkers in vegetarians. Therefore, the aims of the current study were compared the plasma concentrations of myeloperoxidase (MPO), metalloproteinase (MMP)-9, MMP-2, tissue inhibitor of MMP (TIMP)-1 and TIMP-2 between healthy vegetarian (Veg) and healthy omnivorous (Omn). Methods Using ELISA and multiplexed bead immunoassay, we measured in plasma from 43 Veg and 41 Omn the cardiovascular biomarkers concentrations cited above. Results We found significant lower concentrations of MPO, MMP-9, MMP-2 and MMP-9/TIMP-1 ratio in Veg compared to Omn (all P < 0.05). Moreover, MMP-9 concentrations were correlated positively with leukocytes and neutrophils count in both groups (all P < 0.05). Conclusion A vegetarian diet is associated with a healthier profile of cardiovascular biomarkers compared to omnivorous. [ABSTRACT FROM AUTHOR]

Background: Indonesian mistletoe grows on various trees. Mango Mistletoes (Dendrophthoe pentandra) is one type of mistletoe that grown on mango tree (.benalu mangga in bahasa Indonesia). Our study used mistletoe as a parasitic plant that has been used for traditional medicine. It has been known that Dendrophtoe pentandra extract (DPE) anti-inflammatory and anticancer. Furthermore, it is necessary to follow-up study in vivo to evaluate the response to treatment of new cancer therapeutic agents. This research aimed to determine the levels of IL-22, myeloperoxide (MPO), proliferation and wild-type p53 expression after the administration of DPE to murine models of CAC. Methods: Mouse colitis associated colon cancer (CAC) was induced firstly by azoxymethane (AOM) and followed by administration of drinking water containing 5 % dextran sodium sulfate (DSS) in a cycle protocol, each cycle consisted of seven days of 5 % DSS in the drinking water and followed by seven days of regular water. This study consists of five treatment groups: I was treated water only (control), II was administrated by (DSS only, without DPE), (III-V) were administrated by DPE (125 mg/kg BW, 250 mg/kg BW and 500 mg/kg BW) respectively. The administrated of DPE were started from the 8th weeks, were continued until 21 weeks. At the end of 21 weeks of the experiment, mice were sacrificed, colon tissue was removed, and then subjected to ELISA, flow cytometry, real-time PCR and histology examination. Results: Administration of DPE 250 mg/kgBW significantly reduce the levels of IL-22 and MPO compared with DSS only group (p< 0.001; p< 0.001). Colonic epithelial cells proliferation of group IV (DPE 250 mg/kgBW) were significantly lower than III and V groups. There was no significant change in the S phase in mice were treated DPE 125 mg/kg BW and 500 mg/kg BW, while administration of DPE 250 mg/kg BW was able to increase the percentage of cells in S phase. The expression of mRNA p53 was up regulated in mice received DPE 125 mg/kg BW. Conclusion: These findings indicate that the DPE could inhibit colonic epithelial cells proliferation through p53 pathway independently. This study also showed that DPE could be potential sources of new therapy. [ABSTRACT FROM AUTHOR]

The forkhead box O (Foxo) family of transcription factors plays a crucial role in cell apoptosis, immune regulation, and tissue development. Foxo1, as the foremost member of the Foxo family, regulates a wide range of molecular signals in many tissues, including tumor, liver, and brain. This study investigated Foxo1 expression at different time points and in different brain areas, and the role of Foxo1 in vivo in regulating inflammatory injury in a rat model of autologous blood-injected cerebral hemorrhage injury. We found that Foxo1 expression peaked at 12 h post-intracerebral hemorrhage (ICH) and in the ipsilateral corpus striatum. Foxo1 knockdown by Foxo1 siRNA decreased ICH injury, improved neurological function, and decreased the expression of inflammatory factors downstream of the Foxo1 pathway, including TLR4, NF-κB, TNF-α, IL-1β, and IL-18. Foxo1 knockdown also decreased the expression and activity of myeloperoxidase, IL-1β, and IL-18. In conclusion, our findings demonstrate that Foxo1 is a key regulator of inflammatory injury in rats after ICH. By identifying the molecular mechanisms of Foxo1/TLR4/NF-κB signaling, we provide a novel rationale for therapeutic approaches to managing inflammatory injury after ICH. [ABSTRACT FROM AUTHOR]

NADPH oxidases (NOX) mediate redox signaling by generating superoxide and/or hydrogen peroxide, which are involved in biosynthetic pathways, e.g. thyroid hormone generation, dityrosine crosslinking, as well as bacterial killing. Data investigating the role of NOX enzymes in cutaneous wound repair is limited and specifically their function in skin myofibroblast expression is unknown. The isoform NOX4 was recently shown to be a pre-requisite for the differentiation of cardiac and pulmonary myofibroblasts. In this study we investigate the role of NOX4 in wound repair using a wound model in NOX4 knockout mice (n=16) and wildtype mice (n=16). Wounds were photographed daily until complete wound closure. Mice were sacrificed at day 3, 7, 14; wound tissue was harvested. NOX4-deficient mice healed significantly slower (22 days, SD=1.9) than wild-type mice (17 days, SD=1.4, p<0.005). However, there was no difference in myofibroblast expression. Strong dityrosine formation was observed, but was significantly weaker in NOX4-/- mice (p<0.05). NOX2, HIF1α and CD31 expression was significantly weaker in NOX4-/- mice (p<0.05). In this study we show for the first time that NOX4 plays a role in cutaneous wound repair. Our data suggests that NOX4 mediates HIF1α expression and neoangiogenesis during wound repair. NOX4 deletion led to a decreased expression of NOX2, implying a role of NOX4 in phagocytic cell recruitment. NOX4 was required for effective wound contraction but not myofibroblast expression. We suggest that myofibroblast contraction in NOX4-deficient mice is less effective in contracting the wound because of insufficient dityrosine-crosslinking of the ECM, providing the first indication for a physiological function of dityrosine crosslinking in higher animals. [ABSTRACT FROM AUTHOR]

Myeloperoxidase (MPO) and MPO-catalyzed hypochlorous acid (HOCl) is elevated in many neurodegenerative diseases, and lead to severe tissue injuries. Nitrite (NO 2 − ) is a widespread inorganic molecule that has recently been proposed as a direct NO donor to exert antioxidant properties in vivo and vitro. Since NO 2 − and MPO (and/or HOCl) were important mediators in brain function and disease, we investigated the effects of NO 2 − on MPO-mediated damage to human neuroblastoma SH-SY5Y cells. Here, we showed that exposure of SH-SY5Y cells to MPO (or HOCl) resulted in a significant loss in viability, ATP and glutathione levels, and treatment of neuronal cells with NO 2 − substantially attenuated MPO (or HOCl)-dependent cellular toxicity. The protective effects of NO 2 − on MPO (or HOCl)-induced cytotoxicity were because that (1) NO 2 − at high concentrations competed effectively with Cl − for MPO, thus limiting OCl − production by the enzyme; (2) HOCl was removed by reacting with NO 2 − , forming less damaging compound; (3) NO 2 − significantly inhibited MPO-mediated inactivation of brain protein (enolase) and protein oxidation. Therefore, NO 2 − could show novel protective effects in some neurodegenerative diseases by preventing MPO-mediated oxidative damage. [ABSTRACT FROM AUTHOR]

Background:Acute pancreatitis is associated with acute lung injury. The aim of the present study is to evaluate alterations of lungs in an experimental model of acute pancreatitis (AP) following both bilio-pancreatic duct obstruction close to the duodenum. Acute pancreatitis is a common disease with significant mortality. This situation makes the need of finding protective factors for the lung parenchyma, imperative. In the present study there is an effort to clarify the role of apigenin, a substance which is well known for its antioxidant and anti-inflammatory effects, on lung injury, following acute pancreatitis in rats.Materials and methods:In the present study, 126 male Wistar-type rats 3–4 months old and 220–350 g weight were used. At time 0 we randomly assigned the following groups: Group Sham: Rats were subjected to virtual surgery. Group Control: Rats were subjected to surgery for induction of acute pancreatitis. Group Apigenin: Rats were subjected to surgery for induction of acute pancreatitis and enteral feeding with apigenin. Immunochemistry for TNF-α and IL-6 as well as MPO activity were measured at predetermined time intervals 6, 12, 24, 48, and 72 h, in order to evaluate architectural disturbances of the lung tissue.Results:From the pathological reports we realized that comparing the control group with the apigenin group, there is an improvement of lung tissue damage following apigenin administration, with statistical significance. Apigenin reduces most histopathological alterations of the pulmonary tissue, reduces MPO and TNF-α activity at 48 hours and, furthermore, reduces IL-6 activity at 72 hours post-administration.Conclusions:Oral Apigenin administration in rats, following experimental induced acute pancreatitis, seems to be protective on the lung tissue. Apigenin administration to humans could potentially ameliorate acute lung injuries. However, special caution is required for humans' use, as more detailed studies are needed. [ABSTRACT FROM AUTHOR]

Metropolitan Planning Organizations (MPOs) throughout the United States are identifying goals and implementation strategies to reduce the impacts of climate change through transportation adaptation initiatives. Using vulnerability assessments as well as adaptation practices that support mitigation, MPOs are beginning to integrate climate change planning into the long range planning process. Evaluating the state-of-the-practice of adaptation planning and adaptation in support of mitigation is useful in that it helps identify gaps and areas of improvement. Therefore, this research investigates the state-of-the-practice of MPO adaptation planning using the Mid-Atlantic region as a case study. Surveys, administered in 2012 and 2014, are used to identify the level of progress of MPOs with regard to climate change adaptation practices as well as barriers before and after Hurricane Sandy. A cross-sectional analysis using GIS (Geographic Information Systems) maps the results of the surveys and spatially compares regional trends. The results of the case study suggest growing interest in adaptation efforts such as floodplain area designations and efforts to enhance coordination and collaboration as transportation jurisdictions respond to the potential climate change impacts. In addition, MPOs with dense, smaller geographic areas prioritize inter-jurisdictional collaboration as high, suggesting that they are more reliant on other agencies to maintain inter-connectivity of transportation networks and further implement adaptation planning practices. [ABSTRACT FROM AUTHOR]

Purpose: The MPO system plays an important role in the control of infections and the deletion of malignant cells. Nevertheless, alternations in the MPO system can lead to DNA damage and carcinogenesis. Polymorphisms in the MPO Gene have been associated with an increased expression of MPO and a higher risk for development of cancer. This study evaluates the association between -463G/A MPO gene polymorphism and the risk for CIN.Methods: The MPO gene polymorphism (-463G/A) was investigated in 616 women with cervical intraepithelial neoplasia and in 206 healthy women. Association between MPO gene polymorphism and risk of cervical intraepithelial neoplasia were analyzed by univariate and multivariable models.Results: No significant difference in genotype distribution of the MPO gene polymorphism was observed in women with CIN and controls (p = 0.4; OR 1.2, 95 % CI 0.8-1.6). A subgroup analysis only including women with CIN did not show an association between -463G/A MPO gene polymorphism and risk for high-grade CIN (CIN 2/3) (p = 0.09; OR 1.5, 95 % CI 0.9-2.3).Conclusions: The investigated MPO gene polymorphism is not associated with risk for the development of cervical intraepithelial neoplasia. [ABSTRACT FROM AUTHOR]

Discovering repetitive patterns is important in a wide range of research areas, such as bioinformatics and human movement analysis. This study puts forward a new methodology to identify, visualise and interpret repetitive motion patterns in groups of Moving Point Objects (MPOs). The methodology consists of three steps. First, motion patterns are qualitatively described using the Qualitative Trajectory Calculus (QTC). Second, a similarity analysis is conducted to compare motion patterns and identify repetitive patterns. Third, repetitive motion patterns are represented and interpreted in a continuous triangular model. As an illustration of the usefulness of combining these hitherto separated methods, a specific movement case is examined: Samba dance, a rhythmical dance with many repetitive movements. The results show that the presented methodology is able to successfully identify, visualize and interpret the contained repetitive motions. [ABSTRACT FROM AUTHOR]

Significant advances have been made in detecting cancer therapeutics-related cardiac dysfunction with serum biomarkers, cardiovascular MRI, echocardiography and multi-modality approaches. Serum biomarkers, notably cardiac troponins and natriuretic peptides, have been evaluated for their prognostic ability in predicting left ventricular dysfunction. Imaging modalities, such as cardiovascular MRI and echocardiography, have been used for cardiac surveillance of patients with cancer undergoing chemotherapy. Developments in imaging, specifically myocardial deformation imaging, also known as strain, have been shown to be sensitive tools in detecting early changes in cardiac function. This review aims to synthesize the evidence that supports emerging serum biomarkers and complementary imaging modalities that continue to enhance the detection of cancer therapeutics-related cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Background: Among the several disorders induced by sepsis, acute kidney injury (AKI) represents the most important economic burden problem that is associated with high mortality and morbidity rates. The aim of this study was to investigate the anti-inflammatory effects of ghrelin in sepsis-induced AKI and the possible role of vagus nerve. Methods: Five groups were included: sham, cecal ligation and puncture (CLP), CLP-ghrelin, CLP-vagotomy and CLP-vagotomy-ghrelin group. Results: Ghrelin treatment immediately after induction of CLP, significantly improved renal Glomerular filtration rate (GFR), serum creatinine, BUN and renal necrosis score as compared to the unprotected CLP group. In addition, ghrelin significantly decreased renal TNF alpha (111.5 ± 10.35 vs. 291.8 ± 15.8 pg/mg ptn), VCAM1 (6.28 ± 1.7 vs. 12.9 ± 1.2 µ/g ptn) and MPO (0.95 ± 0.13 vs. 2.5 ± 0.4 µ/g ptn) without significant increase in renal IL-10. Those effects were abolished by vagotomy. Conclusion: We concluded that ghrelin could represent new therapeutic window in early treatment of sepsis-induced AKI and this could be mainly due to its anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Cervical cancer is the fourth most common cancer affecting women worldwide, according to the latest IARC release with 528 000 new cases every year. Infection by high-risk human papillomavirus (HPV) is necessary but not sufficient for progression to cancer. Epithelial tissues, the target of HPV infection, are heavily exposed to reactive oxygen species (ROS). Hypochlorous acid (HOCl) is a very potent ROS, and it is produced by myeloperoxidase ( MPO). MPO, a lysosomal enzyme expressed in polymorphonuclear neutrophils (PMN), has the potential to kill HPV transformed cells, as a component of an intercellular induced-apoptosis pathway. This enzyme catalyzes the production of HOCl in the presence of hydrogen peroxide (HO). The HO produced by the Doderlein's bacillus will interact with MPO, contributing to the intercellular induced-apoptosis pathway. We studied a functional polymorphism in the promoter region of MPO (G463A) and how it may affect the risk of developing cervix cancer. A sample of 100 patients with invasive cervical cancer and 122 control women were genotyped for MPO polymorphism by PCR-RFLP method. The statistical method used was χ. We found that women with the GG genotype had lower risk for cervical cancer than the women who displayed the heterozygous genotype GA (OR = 0.546, 95 % CI = 0.315-0.939, p = 0.028, OR = 2.210, 95 % CI = 1.257-3.886, p = 0.008, respectively). The genotype that leads to a higher concentration of ROS (GG) presents itself as a protection factor in comparison to the homozygous genotype (AA). This can be explained by the interaction of HOCl and superoxide of transformed cells that will generate apoptosis-inducing hydroxyl radicals. [ABSTRACT FROM AUTHOR]

The neutrophil myeloperoxidase (MPO) promotes the oxidative stress by the production of active chlorinated molecules. The aim of this study was to investigate the association between MPO promoter polymorphic variants (rs2243827 and rs2333227) and, its serum level in patients with the stenosis of coronary arteries. Furthermore, a system approach was applied to create the MPO transcription factor network. A total of one hundred fifty six subjects (controls, stenosis < 5%, n = 71 and patients, stenosis > 70%, n = 85) undergoing coronary angiography were recruited. The polymorphic haplotypes and serum MPO level were identified using ARMS-PCR and ELISA techniques, respectively. The MPO transcription factor network was primarily created with PSICQUIC and ChIP data and, was improved with the predicted transcription factors. The regression analyses did not show an association between the serum MPO level and the extent of stenosis in coronary arteries. The network showed that the predicted transcription factors at the flanking regions of polymorphic variants are not directly interacted to MPO. In conclusion, the population and prediction studies showed no association between the serum MPO level, the promoter high-frequency polymorphic frequencies and the extent of stenosis in coronary arteries. A gene sub-cluster with MYB as central node was suggested to be involved with MPO on the transcription factor network. [ABSTRACT FROM AUTHOR]

Background: 50% to 60% of the people who have recovered from the first episode of depression experience a relapse. The immune system of the people suffering from depression is in a permanent state of pathological pro-inflammatory readiness. There are some reports that depressive episodes cause sensitization of immune-inflammatory pathways and that staing of depression (e.g. number of depressive episodes) is correlated with immune-inflammatory markers. The main objective of the study was to delineate whether recurrent major depression (rDD) is characterized by alterations in selected immune-inflammatory biomarkers as compared with first episode of depression (ED-I), i.e. expression of mRNA and enzymatic activity of manganese superoxide dismutase (MnSOD, SOD-2), myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS, NOS-2), and cyclooxygenase-2 (COX-2). Methods: The study was carried out in a group of 131 patients: ED-I group -- 42 patients, rDD group -- 89 patients. Depression severity was assessed with the 17-item Hamilton Depression Rating Scale (HDRS). The number of depression episodes and the disease duration periods were recorded in each patient. For the patients, HDRS was administered at admission during the symptomatic phase, which would generally be either before or shortly after modification of the previous antidepressant drug regimen. Reassessment of the mental condition was conducted after 8 weeks of the pharmacological treatment also with the use of the HDRS scale. Results: No significant statistical differences were found between the analysed groups as regards the intensity of depressive disorders. No differences in the expression of MnSOD, MPO, COX-2 and i-NOS genes on the level of both mRNA and protein were observed between both groups. No significant interrelation was noticed between the number of depression episodes experienced and the expression of selected genes on the mRNA level and protein level. Conclusions: There is no significant difference in MnSOD, MPO, COX-2 and i-NOS between patients with recurrent depressive disorders and those in a first episode of depression. These findings suggest that these enzymes are trait markers of depression and are not related to staging of depression. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of 5-ASA-nanoparticles (NP) on TNBS-induced colitis in rats. Methods: Twenty-four BALB/c rats were randomized into normal control group, colitis group, 5-ASA group, and 5-ASA-NP group, with six rats in each group. 5-ASA, 5-ASA-NP and normal saline solution were oral administrated respectively on day 2-7 after the establishment of colitis. On day 8, all animals were sacrificed. The change of body weight, weight to length ratio of colon, and macroscopic and pathologic score of colon were assessed. MPO activity of colonic tissue was measured. Results: Compared with normal group, the DAI, macroscopic and pathologic scores, MPO activity in colonic tissue in TNBS-control group increased significantly. In rats treated with 5-ASA or5-ASA-NP, all the above-mentioned indices decreased significantly, and efficacy of 5-ASA-NP was almost the same as 5-ASA (50mg/Kg). Conclusion: 5-ASA-NP prepared by supercritical dispersion has significant effect on TNBS-induced colitis in rats with lower side effects, which suggested that it might be a potential therapeutic strategy for IBD. [ABSTRACT FROM AUTHOR]

Background It is demonstrated that levels of protein-bound chlorotyrosine, nitrotyrosine and myeloperoxidase (MPO), a protein that catalyzes generation of chlorinating and nitrating oxidants, serve as independent predictors of cardiovascular disease. Methods Immunoprecipitation and Western blot were used to analyze protein concentration, nitration and chlorination. LC-MS/MS was used to identify nitrated and chlorinated sites of Tyr from immunoprecipitated serum proteins. Results Apolipoprotein A-I (apoA-I), the primary protein constituent of high density lipoprotein (HDL), was identified as a selective target for MPO-catalyzed nitration and chlorination in patients with type 2 diabetes. The serum proteins from diabetic subjects showed that the levels of apoA-I nitration and chlorination were clearly increased, whereas apoA-I concentration and cholesterol efflux activity were significantly decreased. MPO as a likely mechanism for oxidative modification of apoA-I in vivo was apparently facilitated by MPO binding to apoA-I. Subsequently, it was found that Tyr 192 was the major nitration and chlorination site in apoA-I from diabetic serum. Further studies in vitro revealed that besides the classic inhibition in cholesterol efflux activities, MPO-catalyzed oxidation could result in a loss of anti-apoptotic activity of lipoprotein. Conclusions ApoA-I undergoes MPO-mediated oxidation in serum from diabetic patients compared to non-diabetic subjects and MPO-catalyzed modification may impair the anti-apoptotic properties of HDL in vitro. [ABSTRACT FROM AUTHOR]

Biochanin A, an O-methylated natural isoflavonoid classified as phytoestrogen, has been reported to show anti-tumorigenesis, anti-oxidation, and anti-inflammatory properties. However, little is known about the effects of biochanin A on cerebral ischemia/reperfusion. In this study, the neuroprotective and anti-inflammatory effects of biochanin A against ischemia/reperfusion injury, as well as the related molecular mechanisms, were investigated in rat models. Male Sprague–Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h, followed by 24 h of reperfusion. Then neurological deficits, infarct volume and brain edema were evaluated. The MPO activity and TNF-α and IL-1β levels in ischemic boundary zone were determined by a spectrophotometer and the enzyme-linked immunosorbent assay (ELISA). The expressions of TNF-α, IL-1β, and phosphorylation of p38 were measured by RT-PCR or Western blotting. Consequently, our findings showed that biochanin A treatment for 14 days had significantly reduced infarct volume and brain edema, and improved neurological deficits in focal cerebral ischemia/reperfusion rats. The MPO activity and TNF-α and IL-1β levels were greatly increased after ischemia/reperfusion injury, while treatment with biochanin A dramatically suppressed these inflammatory processes. Furthermore, biochanin A attenuated the increase in p-p38 level in the ischemia/reperfusion brain tissue. Taken together, biochanin A has been shown to have neuroprotective effects in cerebral ischemia/reperfusion, and the mechanisms may correlate with inhibiting inflammatory response, as well as the inactivation of p38 signaling pathway. [ABSTRACT FROM AUTHOR]

AIM: To assess plasma myeloperoxidase (MPO) levels in autistic children and to test the hypothesis that there is an association between decreased MPO concentration and probiotic therapy. SUBJECTS AND METHODS: Plasma from 49 autistic children (39 males; mean age 11.4 years) (17 with diagnosed gastrointestinal (GI) disease -- chronic diarrhea and/or constipation (10 of these GI patients were taking probiotics) and 26 receiving probiotic therapy) and 36 neurotypical controls (29 males; mean age 10.2 years; controls were not assessed for GI disease) were tested for MPO plasma concentration using Enzyme Linked Immunosorbent Assays (ELISAs). Plasma concentration of MPO in autistic individuals was compared to plasma concentration of copper and zinc. RESULTS: We found that individuals with autism, receiving no therapy, did not have significantly lower plasma MPO levels when compared to controls. In the autistic group, MPO levels were significantly lower in individuals taking probiotic therapy. In addition, plasma copper levels were significantly lower in autistic individuals taking probiotics compared to those not taking probiotics, but plasma zinc levels were not different in the probiotic group. DISCUSSION: These results suggest a relationship between low MPO levels found in a group of autistic individuals and probiotic therapy. By possibly changing gut bacterial flora and thereby changing absorption properties in the gut, probiotic therapy was also associated with lower copper levels. [ABSTRACT FROM AUTHOR]

Background Sepsis causes neutrophil sequestration in the lung which leads to acute lung injury (ALI). Radix Ginseng (RG), a traditional herb used as herbal remedy in eastern Asia for thousands of years, which has been traditionally used in China to improve blood circulation and ameliorate pathological hemostasis. This study investigated whether Ginsenoside Rb1, the main components of RG, can attenuate ALI induced by LPS. Methods In vivo, 30 male Wistar rats were divided into three groups (n = 10 each groups) on the basis of the reagent used, which were subjected to LPS injection with or without Ginsenoside Rb1 (5mg/kg) treatments to induce ALI model. Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, the number of myeloperoxidase (MPO) positive cells, immunohistochemical analysis of intercellular adhesion molecule-1 (ICAM-1), gene expression of ICAM-1, ultrastructure changes of pulmonary microvasculature, concentration of inflammatory markers and in plasma. In vitro, pulmonary microvascular endothelial cells (PMVECs) were stimulated with LPS in the presence and absence of Ginsenoside Rb1 (50mM), nuclear factor-κB (NF-κB) p65 was measured by immunocytochemistry staining and western blotting. Results Infusion of LPS induced lung injury, in vivo, as demonstrated by pulmonary edema with infiltration of neutrophils and hemorrhage, the increase in lung W/D ratio, the number of MPO positive cells, the level of inflammatory markers such as TNF-α, MCP-1 and IL-8, enhanced expression of ICAM-1 and ICAM-1 gene. Moreover, resulted in the changes of intercellular junctions in the endothelial cells of pulmonary microvasculature. In vitro, the significant increased release of NF-κB p65 and its subsequent translocation into the nucleus in PMVECs were observed. In contrast, Ginsenoside Rb1 treatment significantly ameliorated the LPS-induced lung injury, as judged by the marked improvement in all these indices. Conclusions These results indicate that Ginsenoside Rb1 attenuated LPS-induced lung injury through an inhibition of the inflammatory signaling pathway, besides the direct inhibitory effect on proinflammatory molecules. [ABSTRACT FROM AUTHOR]

Selenium (Se) is an essential micronutrient that plays a critical role in anti-inflammatory processes and antioxidant defense system. In this study, we investigated the effects of dietary selenium deficiency on lipopolysaccharide (LPS)-induced mastitis in mouse models. Se content in the liver was assessed by fluorescent atomic absorption spectrometry. Glutathione peroxidase (GPx) activity in the blood, myeloperoxidase (MPO) activity, tumor necrosis actor alpha (TNF-α), and interleukin (IL)-1β in the supernatant of the mammary tissue were determined according to the corresponding kits. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions were evaluated by Western blotting. The results showed that the Se-deficient mouse model was successfully replicated, and selenium deficiency exacerbated mammary gland histopathology, increased the expressions of TNF-α and IL-1β, and facilitated the activation of iNOS and COX-2 in LPS-induced mouse mastitis. In conclusion, our studies demonstrated that selenium deficiency resulted in more severe inflammatory response in LPS-induced mouse mastitis. [ABSTRACT FROM AUTHOR]

Clinical immunology is in the Netherlands a separate clinical specialty within internal medicine and pediatrics. Clinical immunologists work closely together with nephrologists, rheumatologists and many other medical specialists. Apart from research and teaching, clinical immunologists are taking care of patients with immune-deficiencies, vasculitides and systemic auto-immune diseases. Clinical immunology in the Netherlands has always been an important contributor to basic and clinical science in the Netherlands. Major scientific contributions were made in the field of Systemic Lupus Erythematosus and ANCA associated vasculitis. These Dutch contributions will be reviewed in this article. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibody (ANCA) are produced against lysozomal constituents and primary granules of myeloid cells (Neutrophiles & monocytes) in some rheumatic diseases and wegner’s granulomtosis (WG). This antibodies not only may related to onset of vasculitis lesions, but also have a valuable diagnostic tool, thus, first we tired to evaluated the prevalence of this antibodies in 65 serum of patients with RA and 42 serum of patients with SLE. By using of indirect immunoflourescence assay (IFA), two staining patterns are recognized: Cytoplasmic (C-ANCA) pattern which in 80% of results from anti-PR3, and prenuclear (P-ANCA) pattern, which can result from any antibody directed to myeloperoxidase (MPO), cathepsin G (CG) lactoferrin (LF), elastsae (HLE) and lysozyme (LZ). The sensitivity and specificity for SLE from 1:128 serum dilution was 8% and 85.1% respectively, and for RA from 1:16 dilution was 32.2% and 87.5% respectively. Of the 19 SLE, ANCA positive patients 18 (94.7%) had P-ANCA and 1 patient (5.3%) had C-ANCA and of the 23 RA, ANCA positive patients, 17 (73.9%) had P-ANCA and 6 patients (26.1%) had C-ANCA.

Morbidity and mortality in response to SARS-CoV-2 infection are significantly elevated in people of advanced age. To understand the underlying biology of this phenotype, we utilize the golden hamster model to compare how the innate and adaptive immune responses to SARS-CoV-2 infection differed between younger and older animals. We find that while both hamster cohorts showed similar virus kinetics in the lungs, the host response in older animals was dampened, with diminished tissue repair in the respiratory tract post-infection. Characterization of the adaptive immune response also revealed age-related differences, including fewer germinal center B cells in older hamsters, resulting in reduced potency of neutralizing antibodies. Moreover, older animals demonstrate elevated suppressor T cells and neutrophils in the respiratory tract, correlating with an increase in TGF-β and IL-17 induction. Together, these data support that diminished immunity is one of the underlying causes of age-related morbidity. [Display omitted] • Aged hamsters show lower innate and repair responses following SARS-CoV-2 infection • Aging results in a diminished adaptive response following SARS-CoV-2 infection • Aged hamsters show enhancement of TGF-β and IL-17, leading to neutrophil recruitment • Neutralizing antibodies generated in aged hamsters show reduced potency Using the hamster model, Oishi et al. report on how age influences the host response to SARS-CoV-2. Older hamsters have a diminished antiviral response and are slower to repair damage induced by infection. These age-related differences correlate with changes in the adaptive immune cell repertoire. [ABSTRACT FROM AUTHOR]

Verdiperstat, a myeloperoxidase (MPO) inhibitor, is a well-known drug used for the treatment of multisystem atrophy. However, its therapeutic effect on acute lung injury (ALI) remains to be elucidated. In this study, the effect of verdiperstat on lipopolysaccharide (LPS)-induced two-hit rat ALI model was studied in vivo. Subsequently, to explore the anti-ALI mechanism of verdiperstat, an LPS-induced injury in human pulmonary microvascular endothelial cells (HMs) was studied in vitro. The continuous administration of verdiperstat at 120 mg/kg for 3 days exerted a protective effect on the LPS-induced two-hit rat ALI model, as reflected by the change in the lung coefficient and lung pathology scores from 0.72 to 0.61 and 6.08 to 4.37, respectively. Furthermore, the values of protective adhesion protein VE-cadherin and tight junction protein claudin 5 changed from 0.42 to 0.97 and 0.25 to 0.72, but MPO, the ratio of N-μ-calpain to μ-calpain, and the distribution of β-catenin in the nucleus changed from 3.04 to 2.17, 0.62 to 0.38 and 2.25 to 0.76, respectively. LPS-induced HMs in vitro also showed similar results, including lower MPO and the distribution of β-catenin in the nucleus, but higher VE-cadherin claudin 5 and N-μ-calpain. Moreover, MPO inhibition resulted in lower μ-calpain activation and lower β-catenin in the nucleus. Our cumulative results suggest that verdiperstat alleviates ALI by strengthening VE-cadherin and claudin 5 through the inhibition of MPO/μ-calpain/β-catenin activation. [Display omitted] [ABSTRACT FROM AUTHOR]

Human mesenchymal stem/progenitor cells (hMSCs) from bone marrow and other tissues are currently being administered to large numbers of patients even though there are no biomarkers that accurately predict their efficacy in vivo. Using a mouse model of chemical injury of the cornea, we found that bone-marrow-derived hMSCs isolated from different donors varied widely in their efficacy in modulating sterile inflammation. Importantly, RT-PCR assays of hMSCs for the inflammation-modulating protein TSG-6 expressed by the TNFα-stimulated gene 6 (TSG-6 or TNFAIP6) predicted their efficacy in sterile inflammation models for corneal injury, sterile peritonitis, and bleomycin-induced lung injury. In contrast, the levels of TSG-6 mRNA were negatively correlated with their potential for osteogenic differentiation in vitro and poorly correlated with other criteria for evaluating hMSCs. Also, a survey of a small cohort suggested that hMSCs from female donors compared with male donors more effectively suppressed sterile inflammation, expressed higher levels of TSG-6, and had slightly less osteogenic potential. [ABSTRACT FROM AUTHOR]

Despite great progress in prevention strategies, pharmacotherapy and interventional treatment of coronary artery disease (CAD), cardiovascular events still constitute the leading cause of mortality and morbidity in the modern world. Traditional risk factors, including hypertension, diabetes mellitus, smoking, obesity, dyslipidemia, and positive family history account for the occurrence of the majority of these events, but not all of them. Adequate risk assessment remains the most challenging in individuals classified into low or intermediate risk categories. Inflammation plays a key role in the initiation and promotion of atherosclerosis and may lead to acute coronary syndrome (ACS) by the induction of plaque instability. For this reason, numerous inflammatory markers have been extensively investigated as potential candidates for the enhancement of cardiovascular risk assessment. This review aims to critically assess the clinical utility of well-established (C-reactive protein [CRP] and fibrinogen), newer (lipoprotein-associated phospholipase A2 [Lp-PLA2] and myeloperoxidase [MPO]) and novel (growth differentiation factor-15 [GDF-15]) inflammatory markers which, reflect different pathophysiological pathways underlying CAD. Although according to the traditional approach all discussed inflammatory markers were shown to be associated with the risk of future cardiovascular events in individuals with and without CAD, their clear clinical utility remains not fully elucidated. Current recommendations of numerous scientific societies predominantly advocate routine assessment of CRP in healthy people with intermediate cardiovascular risk. However, these recommendations substantially vary in their strength among particular societies. These discrepancies have a multifactorial background, including: (i) the strong prognostic value of CRP supported by solid scientific evidence and proven to be comparable in magnitude with that of total and high-density lipoprotein cholesterol, or hypertension, (ii) favourable analytical characteristics of commercially available CRP assays, (iii) lack of CRP specificity and causal relationship between CRP concentration and cardiovascular risk, and (iv) CRP dependence on other classical risk factors. Of major importance, CRP measurement in healthy men ≥50 years of age or healthy women ≥60 years of age with low-density lipoprotein cholesterol <130 mg/dL may be helpful in the selection of patients for statin therapy. Additionally, evaluation of CRP and fibrinogen or Lp-PLA2 may be considered to facilitate risk stratification in ACS patients and in healthy individuals with intermediate cardiovascular risk, respectively. Nevertheless, the clinical utility of CRP requires further investigation in a broad spectrum of CAD patients, while other promising inflammatory markers, particularly GDF-15 and Lp-PLA2, should be tested in individuals both with and without established CAD. Further studies should also focus on novel performance metrics such as measures of discrimination, calibration and reclassification, in order to better address the clinical utility of investigated biomarkers and to avoid misleadingly optimistic results. It also has to be emphasized that, due to the multifactorial pathogenesis of CAD, detailed risk stratification remains a complex process also involving, beyond assessment of inflammatory biomarkers, the patient's clinical characteristics, results of imaging examinations, electrocardiographic findings and other laboratory parameters (e.g. lipid profile, indices of renal function, markers of left ventricular overload and fibrosis, and biomarkers of myocardial necrosis, preferably cardiac troponins). [ABSTRACT FROM AUTHOR]

Individual responses in creatine kinase (CK) release after eccentric exercise are divergent. This study aimed to identify whether this could be related to selected humoral or intramuscular inflammatory factors. Twenty-three subjects were divided into non-exercising (n = 5) and downhill run (DHR; n = 18) groups (12 . 5 min, 10% decline at 15 km/h). Blood samples were analyzed for white blood cell differential count, CK, myoglobin, tumor necrosis factor-α, granulocyte colony-stimulating factor, interleukin (IL)-1β, IL-6, and IL-10. Muscle biopsies were analyzed for signal transducer and activator of transcription-3 (STAT3), IκΒα, and myeloperoxidase (MPO). DHR participants clustered as early (DHR1) recovery, biphasic response (DHR2), or classic delayed exaggerated CK response (DHR3), with a delayed CK peak (4784 ± 1496 U/L) on day 4. For DHR1 and DHR2, CK peaked on day 1 (DHR1: 1198 ± 837 U/L) or on day 1 and day 4 (DHR2: 1583 ± 448 U/L; 1878 ± 427 U/L), respectively. Immediately post-DHR, IL-6 increased in DHR2 and DHR3 whereas IL-10 increased in all DHR groups. STAT3 signaling increased for DHR1 and DHR2 at 4 h, but MPO at day 2 only in DHR2. Objective cluster analysis uncovered a group of subjects with a characteristic biphasic CK release after DHR. The second elevation was related to their early cytokine response. The results provide evidence that early responses following eccentric exercise are indicative of later variation. [ABSTRACT FROM AUTHOR]