Plasma concentrations of thioredoxin, thioredoxin reductase and peroxiredoxin-4 can identify high risk patients and predict outcome in patients with acute coronary syndrome: A clinical observation.

BACKGROUND: Oxidative stress is a pathological feature of acute coronary syndrome (ACS), a complex disease with varying clinical outcomes. Surrogate biomarkers of oxidative stress including, peroxiredoxin-2 (PRDX2), PRDX4, thioredoxin (TRX) and thioredoxin reductase (TRXR) were measured in ACS patients at presentation and follow-up, to assess their clinical utility in diagnosis and risk stratification. METHODS: Plasma from 145 participants (80 ACS and 65 healthy) at diagnosis, 1-3 month (first) and 6-month follow-up (second) was analysed by ELISA. ACS patients were monitored for 12-months. RESULTS: ACS patients at diagnosis had significantly higher concentrations of TRX (p < 0.05), TRXR (p < 0.01) and PRDX4 (p < 0.01), compared to healthy donors. This was increase was driven by non-ST elevated myocardial infarction for TRX (p < 0.01) and PRDX4 (p < 0.05). For TRXR, ACS females were significantly higher than males (p < 0.05). TRX was also higher in older females (>55 years) at diagnosis (p < 0.05). At first follow-up, TRX had lowered, whereas PRDX4 remained significantly high (p < 0.05). Stratification of ACS patients according to percutaneous coronary intervention (PCI) revealed that TRXR was significantly higher in patients receiving PCI to the right coronary artery (p < 0.05). Whereas both TRXR (p < 0.01) and PRDX4 (p < 0.01) were significantly higher in patients receiving PCI to the left anterior descending (LAD) artery. ACS patients who had plasma TRX >13.40 ng/ml at second follow-up were at high risk of readmission (p < 0.05), as were patients with TRXR of <1000 pg/ml at diagnosis having PCI to the LAD (p < 0.05). CONCLUSION: This study indicates that TRX, TRXR and PRDX4 may have clinical utility for ACS stratification.

High intensity interval exercise increases the frequency of peripheral PD-1+ CD8+ central memory T-cells and soluble PD-L1 in humans.

Exercise can exert anti-inflammatory effects in an intensity-dependent manner; however, the mechanisms mediating these effects are continually being established. Programme Death Receptor-1 (PD-1) is a membrane bound receptor that maintains immune tolerance by dampening immune cell interactions, such as those mediated by cytotoxic T-cell lymphocytes (CD8+). The aim of this study was to characterise sub-populations of CD8+ T-cells with regards to their expression of PD-1 before and immediately after exercise. Interleukin (IL)-6, soluble PD-1 (sPD-1) and its ligand (sPD-L1) were also quantified in plasma. Eight individuals (mean â€‹± â€‹SD: age 29 â€‹± â€‹5 years; BMI 24.2 â€‹± â€‹3.4 â€‹kg â€‹m2; V ˙ O2max 44.5 â€‹± â€‹6.4 â€‹ml â€‹kg-1·min-1) undertook two time and energy-matched cycling bouts in a counterbalanced study design: one of moderate intensity (MOD) and a bout of high intensity interval exercise (HIIE). Both MOD and HIIE increased the number, but not the proportion of circulating CD8+ PD-1+ cells, with no differences between trials. Within the CD8+ PD-1+ pool, the expression of PD-1 increased on central memory cells following HIIE only (fold change: MOD 1.0 vs HIIE +1.4), as well the concentration of CD8+PD-1+ memory cells within the circulation (cells/uL: MOD -0.4 vs HIIE +5.8). This response composed a very small part of the exercise-induced CD8+ lymphocytosis (Pre-Ex: 0.38% to Post-Ex: 0.69%; p â€‹> â€‹0.05). sPD-L1 and IL-6 concentration increased in tandem following MOD and HIIE (r â€‹= â€‹0.57; P â€‹= â€‹0.021), with a reciprocal decline in sPD-1 observed. The current data demonstrate that PD-1+ CD8+ lymphocytes were mobilised following both MOD and HIIE. Both the number of central memory CD8+ T-cells expressing PD-1 and the expression level on these cells were increased following HIIE only. This intensity-dependent phenotypic response, in conjunction with increased circulatory sPD-L1 may represent an aspect of the anti-inflammatory response to exercise and warrants further investigation.

One week of magnesium supplementation lowers IL-6, muscle soreness and increases post-exercise blood glucose in response to downhill running.

PURPOSE: Magnesium supplementation modulates glucose metabolism and inflammation, which could influence exercise performance and recovery. This study investigated the effect of magnesium intake on physiological responses and performance during eccentric exercise and recovery. METHODS: Nine male recreational runners completed a counterbalanced, double-blind, placebo-controlled, cross-over study, registered at ClinicalTrial.gov. Participants consumed low magnesium diets and were supplemented with 500 mg/day of magnesium (SUP) or placebo (CON) for 7 days prior to a 10 km downhill (- 10%) running time trial (TT), separated by a 2-week washout period. At baseline and 24 h post-TT, maximal muscle force was measured. Interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R) and creatine kinase (CK) were measured at rest, 0 h, 1 h and 24 h post-TT. Muscle soreness was measured at the previous times plus 48 h and 72 h post. Glucose and lactate were measured during the TT. RESULTS: The main effect of condition was detected for IL-6 (SUP: 1.36 ± 0.66 vs CON: 2.06 ± 1.14 pg/ml) (P < 0.05, η2 = 0.54), sIL-6R (SUP: 27,615 ± 8446 vs CON: 24,368 ± 7806 pg/ml) (P < 0.05, η2 = 0.41) and muscle soreness (P < 0.01, η2 = 0.67). Recovery of blood glucose and muscle soreness were enhanced in SUP post-TT. There were no differences in glucose and lactate during the TT, or post measures of CK and maximal muscle force. CONCLUSION: Magnesium supplementation reduced the IL-6 response, enhanced recovery of blood glucose, and muscle soreness after strenuous exercise, but did not improve performance or functional measures of recovery.

Characterization of extracellular redox enzyme concentrations in response to exercise in humans.

Redox enzymes modulate intracellular redox balance and are secreted in response to cellular oxidative stress, potentially modulating systemic inflammation. Both aerobic and resistance exercise are known to cause acute systemic oxidative stress and inflammation; however, how redox enzyme concentrations alter in extracellular fluids following bouts of either type of exercise is unknown. Recreationally active men (n = 26, mean ± SD: age 28 ± 8 yr) took part in either: 1) two separate energy-matched cycling bouts: one of moderate intensity (MOD) and a bout of high intensity interval exercise (HIIE) or 2) an eccentric-based resistance exercise protocol (RES). Alterations in plasma (study 1) and serum (study 2) peroxiredoxin (PRDX)-2, PRDX-4, superoxide dismutase-3 (SOD3), thioredoxin (TRX-1), TRX-reductase and interleukin (IL)-6 were assessed before and at various timepoints after exercise. There was a significant increase in SOD3 (+1.5 ng/mL) and PRDX-4 (+5.9 ng/mL) concentration following HIIE only, peaking at 30- and 60-min post-exercise respectively. TRX-R decreased immediately and 60 min following HIIE (-7.3 ng/mL) and MOD (-8.6 ng/mL), respectively. In non-resistance trained men, no significant changes in redox enzyme concentrations were observed up to 48 h following RES, despite significant muscle damage. IL-6 concentration increased in response to all trials, however there was no significant relationship between absolute or exercise-induced changes in redox enzyme concentrations. These results collectively suggest that HIIE, but not MOD or RES increase the extracellular concentration of PRDX-4 and SOD3. Exercise-induced changes in redox enzyme concentrations do not appear to directly relate to systemic changes in IL-6 concentration.NEW & NOTEWORTHY Two studies were conducted to characterize changes in redox enzyme concentrations after single bouts of exercise to investigate the emerging association between extracellular redox enzymes and inflammation. We provide evidence that SOD3 and PRDX-4 concentration increased following high-intensity aerobic but not eccentric-based resistance exercise. Changes were not associated with IL-6. The results provide a platform to investigate the utility of SOD3 and PRDX-4 as biomarkers of oxidative stress following exercise.

Field Evaluation of a Competitive Lateral-Flow Assay for Detection of Alternaria brassicae in Vegetable Brassica Crops.

On-site detection of inoculum of polycyclic plant pathogens could potentially contribute to management of disease outbreaks. A 6-min, in-field competitive immunochromatographic lateral flow device (CLFD) assay was developed for detection of Alternaria brassicae (the cause of dark leaf spot in brassica crops) in air sampled above the crop canopy. Visual recording of the test result by eye provides a detection threshold of approximately 50 dark leaf spot conidia. Assessment using a portable reader improved test sensitivity. In combination with a weather-driven infection model, CLFD assays were evaluated as part of an in-field risk assessment to identify periods when brassica crops were at risk from A. brassicae infection. The weather-driven model overpredicted A. brassicae infection. An automated 7-day multivial cyclone air sampler combined with a daily in-field CLFD assay detected A. brassicae conidia air samples from above the crops. Integration of information from an in-field detection system (CLFD) with weather-driven mathematical models predicting pathogen infection have the potential for use within disease management systems.

Impact of shortened crop rotation of oilseed rape on soil and rhizosphere microbial diversity in relation to yield decline.

Oilseed rape (OSR) grown in monoculture shows a decline in yield relative to virgin OSR of up to 25%, but the mechanisms responsible are unknown. A long term field experiment of OSR grown in a range of rotations with wheat was used to determine whether shifts in fungal and bacterial populations of the rhizosphere and bulk soil were associated with the development of OSR yield decline. The communities of fungi and bacteria in the rhizosphere and bulk soil from the field experiment were profiled using terminal restriction fragment length polymorphism (TRFLP) and sequencing of cloned internal transcribed spacer regions and 16S rRNA genes, respectively. OSR cropping frequency had no effect on rhizosphere bacterial communities. However, the rhizosphere fungal communities from continuously grown OSR were significantly different to those from other rotations. This was due primarily to an increase in abundance of two fungi which showed 100% and 95% DNA identity to the plant pathogens Olpidium brassicae and Pyrenochaeta lycopersici, respectively. Real-time PCR confirmed that there was significantly more of these fungi in the continuously grown OSR than the other rotations. These two fungi were isolated from the field and used to inoculate OSR and Brassica oleracea grown under controlled conditions in a glasshouse to determine their effect on yield. At high doses, Olpidium brassicae reduced top growth and root biomass in seedlings and reduced branching and subsequent pod and seed production. Pyrenochaeta sp. formed lesions on the roots of seedlings, and at high doses delayed flowering and had a negative impact on seed quantity and quality.

Densovirus induces winged morphs in asexual clones of the rosy apple aphid, Dysaphis plantaginea.

Winged morphs of aphids are essential for their dispersal and survival. We discovered that the production of the winged morph in asexual clones of the rosy apple aphid, Dysaphis plantaginea, is dependent on their infection with a DNA virus, Dysaphis plantaginea densovirus (DplDNV). Virus-free clones of the rosy apple aphid, or clones infected singly with an RNA virus, rosy apple aphid virus (RAAV), did not produce the winged morph in response to crowding and poor plant quality. DplDNV infection results in a significant reduction in aphid reproduction rate, but such aphids can produce the winged morph, even at low insect density, which can fly and colonize neighboring plants. Aphids infected with DplDNV produce a proportion of virus-free aphids, which enables production of virus-free clonal lines after colonization of a new plant. Our data suggest that a mutualistic relationship exists between the rosy apple aphid and its viruses. Despite the negative impact of DplDNV on rosy apple aphid reproduction, this virus contributes to their survival by inducing wing development and promoting dispersal.

A bacmid approach to the genetic manipulation of granuloviruses.

A Cydia pomonella granulovirus (CpGV) bacmid has been constructed, which allows rapid and efficient production of recombinant baculoviruses in Escherichia coli. An 8.6kbp bacterial DNA cassette derived from the AcMNPV Bac-to-Bac system was ligated into a unique PacI restriction site within an intergenic region flanking the DNA ligase gene of the CpGV genome. The CpGV bacmids produced in E. coli were transfected into a CpGV-permissive C. pomonella cell line and the transfected cells fed to larvae to amplify the virus. The enhanced green fluorescent protein (EGFP) gene under the constitutive Drosophila heat-shock promoter was transposed into the mini-attTn7 transposition site, using a modified pFASTBAC donor plasmid, to generate a recombinant CpGV bacmid which caused infected larvae to glow under UV light. Targeted homologous recombination was also achieved in a recombinant proficient E. coli strain (BJ5183). A chloramphenicol acetyl transferase (CAT) gene replaced the cathepsin (v-cath) gene in the bacmid to produce a v-cath-deletion mutant. This is the first published report of a granulovirus bacmid, which will allow easy manipulation of the CpGV genome, enabling future studies on granulovirus genes and biology.