Short-term and lifelong exercise training lowers inflammatory mediators in older men
- Authors: Hayes, Lawrence , Herbert, Peter , Sculthorpe, Nicholas , Grace, Fergal
- Date: 2021
- Type: Text , Journal article
- Relation: Frontiers in Physiology Vol. 12, no. (2021), p.
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- Description: Increased basal low-grade inflammation is observed with advancing age, which is augmented by physical inactivity. However, data regarding the influence of lifelong exercise training and particularly high-intensity interval training (HIIT) on inflammatory mediators in older men are scarce. Therefore, we examined effects of 6weeks of aerobic preconditioning followed by 6weeks of HIIT on inflammatory mediators [interleukin (IL)-6, homocysteine, and high-sensitivity C-reactive protein (hsCRP)] in previously sedentary older men (SED) and masters athletes (LEX). Further, we investigated whether SED exhibited greater basal inflammatory biomarkers compared to LEX. Twenty-two men (aged 62±2years) participated in the SED group, while 17 age-matched LEX men (aged 60±5years) also participated as a positive comparison group. In SED, preconditioning (P=0.030, d=0.34) and HIIT (P=0.030, d=0.48) caused a reduction in IL-6 compared to enrollment. SED homocysteine did not change throughout (P>0.57; d<0.26), while the decrease in hsCRP after preconditioning (P=0.486, d=0.25) and after HIIT (P=0.781, d=0.23) compared to enrollment was small. HIIT did not influence IL-6 or hsCRP in LEX (all P>0.42; d<0.3). Homocysteine increased from enrollment to post-HIIT in LEX (P=0.144, d=0.83), but all other perturbations were trivial. IL-6 and hsCRP were greater in SED than LEX throughout the investigation (all P<0.029; d>0.72), but homocysteine was not different (all P >0.131; d<0.41). Results of this study suggest moderate-intensity aerobic exercise and HIIT lowers IL-6 (and possible hsCRP) in previously sedentary older men. Moreover, lifelong exercise is associated with reduced concentrations of some inflammatory biomarkers in older males, and therefore, physical activity, rather than age per se, is implicated in chronic low-grade inflammation. Moreover, physical inactivity-induced inflammation may be partly salvaged by short-term exercise training. © Copyright © 2021 Hayes, Herbert, Sculthorpe and Grace.
Inflammation and Oral Contraceptive Use in Female Athletes Before the Rio Olympic Games
- Authors: Larsen, Brianna , Cox, Amanda , Colbey, Candice , Drew, Michael , McGuire, Helen , Fazekas de St Groth, Barbara , Hughes, David , Vlahovich, Nicole , Waddington, Gordon , Burke, Louise , Lundy, Bronwen , West, Nicholas , Minahan, Clare
- Date: 2020
- Type: Text , Journal article
- Relation: Frontiers in Physiology Vol. 11, no. (2020), p.
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- Description: This study investigated the association between synthetic ovarian hormone use [i.e., the oral contraceptive (OC) pill] and basal C-reactive protein (CRP), peripheral blood immune cell subsets, and circulating pro- and anti-inflammatory cytokine concentrations in elite female athletes. Elite female athletes (n = 53) selected in Rio Summer Olympic squads participated in this study; 25 were taking an OC (AthletesOC) and 28 were naturally hormonally cycling (AthletesNC). Venous blood samples were collected at rest for the determination of sex hormones, cortisol, CRP, peripheral blood mononuclear memory and naïve CD4+ T-cells, CD8+ T-cells and natural killer cells, as well as pro- and anti-inflammatory cytokine concentrations. C-reactive protein concentrations were elevated (p < 0.001) in AthletesOC (median = 2.02, IQR = 3.15) compared to AthletesNC (median = 0.57, IQR = 1.07). No differences were reported for cortisol, cytokines, or PBMC immune cell subsets, although there was a trend (p = 0.062) for higher IL-6 concentrations in AthletesNC. Female Olympians had substantially higher CRP concentrations, a marker of inflammation and tissue damage, before the Rio Olympic Games if they used an OC. Future research should examine the potential consequences for athlete performance/recovery so that, if necessary, practitioners can implement prevention programs. © Copyright © 2020 Larsen, Cox, Colbey, Drew, McGuire, Fazekas de St Groth, Hughes, Vlahovich, Waddington, Burke, Lundy, West and Minahan.
Long-term aerobic exercise improves vascular function into old age : A systematic review, meta-analysis and meta regression of observational and interventional studies
- Authors: Campbell, Amy , Grace, Fergal , Ritchie, Louise , Beaumont, Alexander , Sculthorpe, Nicholas
- Date: 2019
- Type: Text , Journal article , Review
- Relation: Frontiers in Physiology Vol. 10, no. FEB (2019), p. 1-16
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- Description: There is an emerging body of literature relating to the effectiveness of frequent aerobic exercise as a prophylactic for age-associated dysfunction of large arteries, yet systematic evaluation and precise estimate of this effect is unknown. We conducted a systematic review and meta-analysis of controlled studies examining flow mediated dilatation (FMD) of athletic older persons and otherwise healthy sedentary counterparts to (i) compare FMD as a determinant of endothelial function between athletes and sedentary individuals and, (ii) summarize the effect of exercise training on FMD in studies of sedentary aging persons. Studies were identified from systematic search of major electronic databases from inception to January 2018. Study quality was assessed before conducting a random effects meta-analysis to calculate a pooled ES (mean difference) with 95% CI's. Thirteen studies [4 interventional (n = 125); 10 cross-sectional [including one study from the interventional analysis; (n = 485)] with age ranges from 62 to 75 years underwent quantitative pooling of data. The majority of study participants were male. Older athletes had more favorable FMD compared with sedentary controls (2.1%; CI: 1.4, 2.8%; P < 0.001). There was no significant improvement in the vascular function of sedentary cohorts following a period of exercise training (0.7%; CI: −0.675, 2.09%; P = 0.316). However, there was a significant increase in baseline diameter from pre to post intervention (0.1 mm; CI: 0.07, 0.13 mm; P < 0.001). In addition, there was no significant difference in endothelial independent vasodilation between the trained and sedentary older adults (1.57%; CI: −0.13, 3.27%; P = 0.07), or from pre to post exercise intervention (1.48%; CI: −1.34, 4.3%; P = 0.3). In conclusion, long-term aerobic exercise appears to attenuate the decline in endothelial vascular function, a benefit which is maintained during chronological aging. However, currently there is not enough evidence to suggest that exercise interventions improve vascular function in previously sedentary healthy older adults.
PCA based population generation for genetic network optimization
- Authors: Youseph, Ahammed , Chetty, Madhu , Karmakar, Gour
- Date: 2018
- Type: Text , Journal article
- Relation: Cognitive Neurodynamics Vol. 12, no. 4 (2018), p. 417-429
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- Description: A gene regulatory network (GRN) represents a set of genes and its regulatory interactions. The inference of the regulatory interactions between genes is usually carried out using an appropriate mathematical model and the available gene expression profile. Among the various models proposed for GRN inference, our recently proposed Michaelis–Menten based ODE model provides a good trade-off between the computational complexity and biological relevance. This model, like other known GRN models, also uses an evolutionary algorithm for parameter estimation. Considering various issues associated with such population based stochastic optimization approaches (e.g. diversity, premature convergence due to local optima, accuracy, etc.), it becomes important to seed the initial population with good individuals which are closer to the optimal solution. In this paper, we exploit the inherent strength of principal component analysis (PCA) in a novel manner to initialize the population for GRN optimization. The benefit of the proposed method is validated by reconstructing in silico and in vivo networks of various sizes. For the same level of accuracy, the approach with PCA based initialization shows improved convergence speed.
Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain
- Authors: Preston, Sarah , Korhonen, Pasi , Mouchiroud, Laurent , Cornaglia, Matteo , McGee, Sean , Young, Neil , Davis, Rohan , Crawford, Simon , Nowell, Cameron , Ansell, Brendan , Fisher, Gillian , Andrews, Katherine , Chang, Bill , Gijs, Martin , Sternberg, Paul , Auwerx, Johan , Baell, Jonathan , Hofmann, Andreas , Jabbar, Abdul , Gasser, Robin
- Date: 2017
- Type: Text , Journal article
- Relation: FASEB Journal Vol. 31, no. 10 (2017), p. 4515-4532
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- Description: As a result of limited classes of anthelmintics and an over-reliance on chemical control, there is a great need to discover new compounds to combat drug resistance in parasitic nematodes. Here, we show that deguelin, a plant-derived rotenoid, selectively and potently inhibits the motility and development of nematodes, which supports its potential as a lead candidate for drug development. Furthermore, we demonstrate that deguelin treatment significantly increases gene transcription that is associated with energy metabolism, particularly oxidative phosphorylation and mitoribosomal protein production before inhibiting motility. Mitochondrial tracking confirmed enhanced oxidative phosphorylation. In accordance, real-time measurements of oxidative phosphorylation in response to deguelin treatment demonstrated an immediate decrease in oxygen consumption in both parasitic (Haemonchus contortus) and free-living (Caenorhabditis elegans) nematodes. Consequently, we hypothesize that deguelin is exerting its toxic effect on nematodes as a modulator of oxidative phosphorylation. This study highlights the dynamic biologic response of multicellular organisms to deguelin perturbation. © FASEB.
Thermodynamic analysis questions claims of improved cardiac efficiency by dietary fish oil
- Authors: Loiselle, Denis , Han, June-Chiew , Goo, Eden , Chapman, Brian , Barclay, Christopher , Hickey, Anthony , Taberner, Andrew
- Date: 2016
- Type: Text , Journal article
- Relation: Journal of General Physiology Vol. 148, no. 3 (2016), p. 183-193
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- Description: Studies in the literature describe the ability of dietary supplementation by omega-3 fish oil to increase the pumping efficiency of the left ventricle. Here we attempt to reconcile such studies with our own null results. We undertake a quantitative analysis of the improvement that could be expected theoretically, subject to physiological constraints, by posing the following question: By how much could efficiency be expected to increase if inefficiencies could be eliminated? Our approach utilizes thermodynamic analyses to investigate the contributions, both singly and collectively, of the major components of cardiac energetics to total cardiac efficiency. We conclude that it is unlikely that fish oils could achieve the required diminution of inefficiencies without greatly compromising cardiac performance.
Evaluating influence of microRNA in reconstructing gene regulatory networks
- Authors: Chowdhury, Ahsan , Chetty, Madhu , Nguyen, Vinh
- Date: 2015
- Type: Text , Journal article
- Relation: Cognitive neurodynamics Vol. 8, no. 3 (2015), p. 251-9
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- Description: Gene regulatory network (GRN) consists of interactions between transcription factors (TFs) and target genes (TGs). Recently, it has been observed that micro RNAs (miRNAs) play a significant part in genetic interactions. However, current microarray technologies do not capture miRNA expression levels. To overcome this, we propose a new technique to reverse engineer GRN from the available partial microarray data which contains expression levels of TFs and TGs only. Using S-System model, the approach is adapted to cope with the unavailability of information about the expression levels of miRNAs. The versatile Differential Evolutionary algorithm is used for optimization and parameter estimation. Experimental studies on four in silico networks, and a real network of Saccharomyces cerevisiae called IRMA network, show significant improvement compared to traditional S-System approach.
MicroRNAs mediate the cardioprotective effect of angiotensin-converting enzyme inhibition in acute kidney injury
- Authors: Rana, Indrajeetsinh , Velkoska, Elena , Patel, Sheila , Burrell, Louise , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: American Journal of Physiology - Renal Physiology Vol. 309, no. 11 (2015), p. F943-F954
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- Description: Cardiovascular disease, including cardiac hypertrophy, is common in patients with kidney disease and can be partially attenuated using blockers of the renin-angiotensin system (RAS). It is unknown whether cardiac microRNAs contribute to the pathogenesis of cardiac hypertrophy or to the protective effect of RAS blockade in kidney disease. Using a subtotal nephrectomy rat model of kidney injury, we investigated changes in cardiac microRNAs that are known to have direct target genes involved in the regulation of apoptosis, fibrosis, and hypertrophy. The effect of treatment with the angiotensin-converting enzyme (ACE) inhibitor ramipril on cardiac microRNAs was also investigated. Kidney injury led to a significant increase in cardiac microRNA-212 and mi- croRNA-132 expression. Ramipril reduced cardiac hypertrophy, attenuated the increase in microRNA-212 and microRNA-132, and significantly increased microRNA-133 and microRNA-1 expression. There was altered expression of caspase-9, B cell lymphoma-2, transforming growth factor-β, fibronectin 1, collagen type 1A1, and forkhead box protein O3, which are all known to be involved in the regulation of apoptosis, fibrosis, and hypertrophy in cardiac cells while being targets for the above microRNAs. ACE inhibitor treatment increased expression of microRNA-133 and microRNA-1. The inhibitory action of ACE inhibitor treatment on increased cardiac NADPH oxidase isoform 1 expression after subtotal nephrectomy surgery suggests that inhibition of oxidative stress is also one of mechanism of ACE inhibitor-mediated cardioprotection. These finding suggests the involvement of microRNAs in the cardioprotective action of ACE inhibition in acute renal injury, which is mediated through an inhibitory action on profibrotic and proapoptotic target genes and stimulatory action on antihypertrophic and antiapoptotic target genes. © 2015 the American Physiological Society. Funding: APP1048285; NHMRC; National Health and Medical Research Council
Stochastic S-system modeling of gene regulatory network
- Authors: Chowdhury, Ahsan , Chetty, Madhu , Evans, Rob
- Date: 2015
- Type: Text , Journal article
- Relation: Cognitive Neurodynamics Vol. 9, no. 5 (2015), p. 535-547
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- Description: Microarray gene expression data can provide insights into biological processes at a system-wide level and is commonly used for reverse engineering gene regulatory networks (GRN). Due to the amalgamation of noise from different sources, microarray expression profiles become inherently noisy leading to significant impact on the GRN reconstruction process. Microarray replicates (both biological and technical), generated to increase the reliability of data obtained under noisy conditions, have limited influence in enhancing the accuracy of reconstruction. Therefore, instead of the conventional GRN modeling approaches which are deterministic, stochastic techniques are becoming increasingly necessary for inferring GRN from noisy microarray data. In this paper, we propose a new stochastic GRN model by investigating incorporation of various standard noise measurements in the deterministic S-system model. Experimental evaluations performed for varying sizes of synthetic network, representing different stochastic processes, demonstrate the effect of noise on the accuracy of genetic network modeling and the significance of stochastic modeling for GRN reconstruction. The proposed stochastic model is subsequently applied to infer the regulations among genes in two real life networks: (1) the well-studied IRMA network, a real-life in-vivo synthetic network constructed within the Saccharomycescerevisiae yeast, and (2) the SOS DNA repair network in Escherichiacoli. © 2015, Springer Science+Business Media Dordrecht.