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Experimental studies show that inflammation impairs the ability to interpret the mental state of another person, denoted theory of mind (ToM). The current study attempted a conceptual replication in states associated with elevated low-grade inflammation, i.e., high body weight and advanced age. Ninety young (M = 26.3 years, SD = 4.1) or older (M = 70.7 years, SD = 4.0) participants with either a normal body mass index (BMI) (M = 22.4, SD = 2.2) or high BMI (M = 33.1, SD = 3.8) completed the Reading the Mind in the Eyes Test (RMET) to assess emotion recognition. Plasma interleukin-6 (IL-6) level was measured to index low-grade inflammation. As anticipated, elevated IL-6 levels were found with higher BMI, although not with increased age. IL-6 was associated with poorer task performance, independent of potential demographic and health confounders (e.g., sex, education, smoking status, alcohol intake, presence of medical conditions, and medication intake). Analyses also revealed an interaction whereby young individuals with a high BMI showed worse RMET performance compared to their normal BMI counterparts, whereas the opposite pattern was found in older individuals. The present observational study replicated experimental results showing that elevated low-grade inflammation is correlated with a lower ability to infer the mental states of others. These findings suggest that also naturalistic conditions of (protracted) low-grade inflammation may alter emotion recognition., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Frailty affects the quality of life of older age adults by limiting mobility, reducing physiological reserve and reducing independence. The frailty phenotype is typically characterised by exhaustion, loss or lack of physical activity, weight loss and weakness, although more recently there have been proposals to extend the frailty criteria to include physiological characteristics such as inflammation, oxidative stress and vascular function. Exercise has the potential to prevent, delay or even reverse frailty, but not all exercise is perceived as suitable for an older age population. The purpose of this study was to test Tai Chi and Zumba Gold® as exercise interventions in older age adults (65 to 75 years old) to improve characteristics related to the frailty phenotype. Muscle strength and flexibility (functional fitness as a measure of weakness), cardiorespiratory fitness, blood pressure, vascular function (FMD), markers of oxidative stress (total antioxidant capacity, malondialdehyde, 8-isoprostane, protein carbonyl), inflammation (CRP) and aspects of wellbeing related to exhaustion were assessed at baseline (pre-), 6 weeks (mid-) and 12 weeks (post-intervention). Both Tai Chi and Zumba Gold® improved systolic blood pressure, vascular function, and functional fitness following the 12 week intervention to a similar extent. Furthermore Antioxidant capacity was significantly increased (303 ± 15.56 vs. 336 ± 18.82 μm; p = 0.0028) and lipid oxidation significantly reduced (36.41 ± 6.4 vs 13.49 ± 2.5 pg/ml; p = 0.0042) after 12 weeks of Tai Chi compared to baseline. Anxiety, physical and mental fatigue decreased in both groups, with a greater decrease in mental fatigue in the Tai Chi group. Taken together, these changes suggest that Tai Chi has the potential to reduce outcomes related to the extended frailty phenotype in older age adults., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Advancing age is a major risk factor for a range of diseases such as, cardiovascular disease, diabetes, cancer and neurodegenerative diseases. In addition, over a third of the population are overweight and obesity is becoming more prevalent in younger people. Ageing and obesity are both linked to a chronic proinflammatory state and elevated oxidative stress, which have both been implicated in cardiovascular and neurodegenerative diseases. Platelets contain all the necessary machinery to process the Amyloid precursor protein AβPP, a pathway thought to be perturbed in Alzheimer's Disease (AD). The ratio of AβPP isoforms present in platelets, and the amount of alpha secretase ADAM10, that works to process AβPP, appear to be associated with cognitive decline and a diagnosis of Alzheimer's disease. The aim of this study was to assess changes in AβPP ratio, ADAM10 and markers of inflammation and oxidative stress with ageing and obesity., Materials and Methods: Ninety participants were recruited to this study to provide one blood sample. Platelet-rich plasma and platelet lysates were collected and the expression of AβPPr, proADAM10 and mADAM10 was assessed by Western blotting. In addition, markers of inflammation (IL-6) and oxidative stress (8-Isoprostane) were assessed in plasma., Results: Participants were placed into one of four groups based on their age and body mass index (Young/Lean, Young/obese, Old/Lean and Old/Obese). IL-6 was able to significantly distinguish obese from lean participants (AUC of 0.80, SE = 0.05, P < 0.001). Plasma isoprostanes were able to distinguish between both young/old (AUC of 0.73, SE = 0.05, P < 0.01), and obese/non-obese participants (AUC of 0.66, SE = 0.01, P < 0.01). Plasma protein carbonyls could distinguish young and old participants (AUC of 0.69, SE = 0.07 P < 0.02). Old Lean participants had significantly lower mADAM10 expression than both Young Lean and Young Obese participants (p < 0.05). Old obese participants had significantly lower proADAM10 expression compared to both Young Lean and Young Obese (p < 0.05). Both mADAM10 and proADAM10 were significantly decreased with advancing age (p < 0.05)., Conclusions: The findings presented in this study provide evidence that blood-based biomarkers related to the pathology of AD are altered with age and obesity in otherwise healthy adults. Ageing was more strongly associated with elevated markers of oxidative stress whereas obesity was associated with elevated inflammatory IL-6., Competing Interests: Declaration of competing interest The authors have no conflict of interest to report., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Dendritic cells (DCs) are important sentinel cells of the immune system responsible for presenting antigen to T cells. Exercise is known to cause an acute and transient increase in the frequency of DCs in the bloodstream in humans, yet there are contradictory findings in the literature regarding the phenotypic composition of DCs mobilised during exercise, which may have implications for immune regulation and health. Accordingly, we sought to investigate the composition of DC sub-populations mobilised in response to acute aerobic exercise. Nine healthy males (age, 21.9 ± 3.6 years; height, 177.8 ± 5.4 cm; body mass, 78.9 ± 10.8 kg; body mass index, 24.9 ± 3.3 kg·m 2 ; V̇O 2 MAX , 41.5 ± 5.1 mL·kg·min -1 ) cycled for 20 min at 80% V̇O 2 MAX . Blood was sampled at baseline, during the final minute of exercise and 30 min later. Using flow cytometry, total DCs were defined as Lineage- (CD3, CD19, CD20, CD14, CD56) HLA-DR+ and subsequently identified as plasmacytoid DCs (CD303+) and myeloid DCs (CD303-). Myeloid DCs were analysed for expression of CD1c and CD141 to yield four sub-populations; CD1c-CD141+; CD1c+CD141+; CD1c+CD141- and CD1c-CD141-. Expression of CD205 was also analysed on all DC sub-populations to identify DCs capable of recognising apoptotic and necrotic cells. Total DCs increased by 150% during exercise (F (1,10)  = 60; p < 0.05, η 2  = 0.9). Plasmacytoid DCs mobilised to a greater magnitude than myeloid DCs (195 ± 131% vs. 131 ± 100%; p < 0.05). Among myeloid DCs, CD1c-CD141- cells showed the largest exercise-induced mobilisation (167 ± 122%), with a stepwise pattern observed among the remaining sub-populations: CD1c+CD141- (79 ± 50%), followed by CD1c+CD141+ (44 ± 41%), with the smallest response shown by CD1c-CD141+ cells (23 ± 54%) (p < 0.05). Among myeloid DCs, CD205- cells were the most exercise responsive. All DC subsets returned to resting levels within 30 min of exercise cessation. These results show that there is a preferential mobilisation of plasmacytoid DCs during exercise. Given the functional repertoire of plasmacytoid DCs, which includes the production of interferons against viral and bacterial pathogens, these findings indicate that exercise may augment immune-surveillance by preferentially mobilising effector cells; these findings have general implications for the promotion of exercise for health, and specifically for the optimisation of DC harvest for cancer immunotherapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The number of peripheral blood B lymphocytes doubles during acute exercise, but the phenotypic composition of this response remains unknown. In two independent exercise studies, using complimentary phenotyping strategies, we investigated the mobilisation patterns of distinct B cell subsets. In study one, nine healthy males (mean±SD age: 22.1±3.4years) completed a continuous cycling bout at 80% V̇O2MAX for 20min. In study two, seven healthy experienced cyclists (mean±SD age: 29.9±4.7years) completed a 30min cycling trial at a workload corresponding to +5% of the individual blood lactate threshold. In study one, CD3-CD19+ B cell subsets were classified into immature (CD27-CD10+), naïve (CD27-CD10-), memory (CD27+CD38-), plasma cells/plasmablasts (CD27+CD38+) and finally, recently purported 'B1' cells (CD27+ CD43+ CD69-). In study two, CD20+ B cells were classified into immature (CD27-IgD-), naïve (CD27-IgD+), and IgM+/IgG+/IgA+ memory cells (CD27+IgD-). Total B cells exhibited a mean increase of 88% (study one) and 60% (study two) during exercise. In both studies, immature cells displayed the greatest increase, followed by memory cells, then naïve cells (study one: immature 130%>mature 105%>naïve 84%; study two: immature 110%>mature 56%>naïve 38%). Our findings show that, unlike T cells and NK cells, B cell mobilisation is not driven by effector status, and, for the first time, that B cell mobilisation during exercise is comprised of immature CD27- IgD-/CD10+ cells., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: The two most common forms of dementia are Alzheimer's disease (AD), and vascular dementia (VaD). In the overlap of biochemical processes which have been identified in AD and VaD, oxidative stress is believed to contribute to the numerous pathologies of both dementias., Design and Methods: This study assessed oxidative damage in total plasma proteins, and isolated LDL in AD patients and age matched controls, in addition total antioxidant capacity (TAC) was measured., Results: Significantly higher LDL protein carbonylation was observed in AD compared to age-matched controls (AD: 4.17+/-0.73 vs. control: 3.85+/-0.86 nmol/mg LDL; p=0.05, 2-tailed Mann-Whitney), in addition to reduced TAC (AD: 924.708+/-174.429 vs. control: 1078.536+/-252.633 microM; p=0.001, 2-tailed Mann-Whitney). No differences were seen in total plasma protein carbonyl content (AD: 3.88+/-0.31 vs. control: 3.98+/-0.48 nmol/mg protein)., Conclusion: The results further support the view that oxidation events in AD may be specific in nature, and represent functional changes to proteins, rather than random global events., ((c) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

We recently reported that methionine-loaded human umbilical vein endothelial cells (HUVECs) exported homocysteine (Hcy) and were associated with hydroxyl radical generation and oxidation of lipids in LDL. Herein we have analysed the Hcy-induced posttranslational modifications (PTMs) of LDL protein. PTMs have been characterised using electrophoretic mobility shift, protein carbonyl ELISA, HPLC with electrochemical detection and Western blotting of 3-nitrotyrosine, and LDL uptake by scavenger receptors on monocyte/macrophages. We have also analysed PTMs in LDL isolated from rheumatoid (RA) and osteo-(OA) arthritis patients with cardiovascular disease (CVD). While reagent Hcy (< 50 microM) promoted copper-catalysed LDL protein oxidation, Hcy released from methionine-loaded HUVECs promoted LDL protein nitration. In addition, LDL nitration was associated with enhanced monocyte/macrophage uptake when compared with LDL oxidation. LDL protein nitration and uptake by monocytes, but not carbonyl formation, was elevated in both RA and OA patients with CVD compared with disease-matched patients that had no evidence of CVD. Moreover, a direct correlation between plasma total Hcy (tHcy) and LDL uptake was observed. The present studies suggest that elevated plasma tHcy may promote LDL nitration and increased scavenger receptor uptake, providing a molecular mechanism that may contribute to the clinical link between CVD and elevated plasma tHcy.

Proteomics, the analysis of expressed proteins, has been an important developing area of research for the past two decades [Anderson, NG, Anderson, NL. Twenty years of two-dimensional electrophoresis: past, present and future. Electrophoresis 1996;17:443-453]. Advances in technology have led to a rapid increase in applications to a wide range of samples; from initial experiments using cell lines, more complex tissues and biological fluids are now being assessed to establish changes in protein expression. A primary aim of clinical proteomics is the identification of biomarkers for diagnosis and therapeutic intervention of disease, by comparing the proteomic profiles of control and disease, and differing physiological states. This expansion into clinical samples has not been without difficulties owing to the complexity and dynamic range in plasma and human tissues including tissue biopsies. The most widely used techniques for analysis of clinical samples are surface-enhanced laser desorption/ionisation mass spectrometry (SELDI-MS) and 2-dimensional gel electrophoresis (2-DE) coupled to matrix-assisted laser desorption ionisation [Person, MD, Monks, TJ, Lau, SS. An integrated approach to identifying chemically induced posttranslational modifications using comparative MALDI-MS and targeted HPLC-ESI-MS/MS. Chem. Res. Toxicol. 2003;16:598-608]-mass spectroscopy (MALDI-MS). This review aims to summarise the findings of studies that have used proteomic research methods to analyse samples from clinical studies and to assess the impact that proteomic techniques have had in assessing clinical samples.

Pre-exercise fat ingestion (i.e., long chain triacylglycerol ingestion 1 to 4 h before exercise), medium-chain triacylglycerols, fish oil, and conjugated linoleic acid have been suggested to alter metabolism to achieve weight loss, alter lipid profiles, or improve performance. However, studies have demonstrated that ingestion of meals with long-chain triacylglycerols before exercise has little or no effect on metabolism and does not alter subsequent exercise performance. Also, medium-chain triacylglycerol supplementation before or during exercise has not been shown to be ergogenic, although this could be related to the small amounts of medium-chain triacylglycerol that can be ingested before gastrointestinal discomfort occurs. Fish oil may improve red blood cell deformability, but these effects are likely to be small and do not seem to influence maximum oxygen delivery or exercise performance. Conjugated linoleic acid has been implicated in weight loss, but based on the results of human studies it must be concluded that the effects of conjugated linoleic acid on body weight loss are far less clear than those observed in animal studies. Most studies have not found any evidence for a beneficial effect of conjugated linoleic acid.

The presence and localisation of dehydroepiandrosterone sulphotransferase was assessed in adult rat brain. The activity of the enzyme was investigated and was found to be approximately four times less than that in rat liver. Rat brain dehydroepiandrosterone sulphotransferase activity was measured as 1.39+/-0.04 nm/microg/min. The protein expression of dehydroepiandrosterone sulphotransferase was evaluated using Western blotting. The presence of a band at 35 kDa signified the presence of this enzyme in adult rat brain. Finally, the localisation of this enzyme was investigated by immunohistochemistry and by assessing activity in nine regions of brain. Immunohistochemistry showed positive staining in the hippocampus and the dendate gyrus, and in the large neurons of the midbrain, indicating the presence of dehydroepiandrosterone sulphotransferase. Western blotting showed the presence of a band in all nine regions, and enzyme activity was highest in the hippocampus, frontal cortex, thalamus and basal ganglia. These results imply that dehydroepiandrosterone and dehydroepiandrosterone sulphate (DHEAS) have a defined role in brain function and are produced in situ independently of the peripheral endocrine system.