Changes in body posture alter plasma nitrite but not nitrate concentration in humans

PURPOSE: This study evaluated the change (Δ) in plasma volume (PV), nitrate [NO3-], and nitrite [NO2-] concentration following changes in posture in the presence and absence of elevated plasma [NO3-] and [NO2-] METHODS: Fourteen healthy participants completed two trials that were preceded by either supplementation with NO3--rich beetroot juice (BR; total of ∼31 mmol NO3-) or no supplementation (CON). Both trials comprised 30 min of lying supine followed by 2 min of standing, 2 min of sitting and 5 min of sub-maximal cycling. Measurements of plasma [NO3-] and [NO2-] were made by gas-phase chemiluminescence and ΔPV was estimated using the Dill and Costill method.RESULTS: Plasma [NO2-] decreased from baseline (CON: 120 ± 49 nM, BR: 357 ± 129 nM) after lying supine for 30 min (CON 77 ± 30 nM; BR 231 ± 92 nM, both P 0.05). PV increased from baseline during the supine phase before decreasing upon standing, sitting, and exercise in both trials (all

Beetroot juice versus chard gel: A pharmacokinetic and pharmacodynamic comparison of nitrate bioavailability

Dietary supplementation with inorganic nitrate (NO3?) has been shown to induce a multitude of advantageous cardiovascular and metabolic responses during rest and exercise. While there is some suggestion that pharmacokinetics may differ depending on the NO3? source ingested, to the best of our knowledge this has yet to be determined experimentally. Here, we compare the plasma pharmacokinetics of NO3?, nitrite (NO2?), and total nitroso species (RXNO) following oral ingestion of either NO3? rich beetroot juice (BR) or chard gels (GEL) with the associated changes in blood pressure (BP). Repeated samples of venous blood and measurements of BP were collected from nine healthy human volunteers before and after ingestion of the supplements using a cross-over design. Plasma concentrations of RXNO and NO2? were quantified using reductive gas-phase chemiluminescence and NO3? using high pressure liquid ion chromatography. We report that, [NO3?] and [NO2?] were increased and systolic BP reduced to a similar extent in each experimental arm, with considerable inter-individual variation. Intriguingly, there was a greater increase in [RXNO] following ingestion of BR in comparison to GEL, which may be a consequence of its higher polyphenol content. In conclusion, our data suggests that while differences in circulating NO2? and NO3? concentrations after oral administration of distinct NO3?-rich supplementation sources are moderate, concentrations of metabolic by-products may show greater-than-expected variability; the significance of the latter observation for the biological effects under study remains to be investigated

Efficacy of high-intensity interval training for improving mental health and health-related quality of life in women with polycystic ovary syndrome

Women with PCOS have substantially greater symptoms of depression and anxiety, and a lower health-related quality of life (HRQoL) compared to women without PCOS. The aim of this study was to determine if high-intensity interval training (HIIT) could provide greater improvements in mental health outcomes than standard moderate-intensity continuous training (MICT). Twenty-nine overweight women with PCOS aged 18–45 years were randomly assigned to 12 weeks of either MICT (60–75% HRpeak, N = 15) or HIIT (> 90% HRpeak, N = 14). Outcome measures included symptoms of depression, anxiety and stress (DASS-21), general HRQoL (SF-36) and PCOS specific HRQoL (PCOSQ) collected at baseline and post-intervention. Reductions in depression (Δ − 1.7, P = 0.005), anxiety (Δ − 3.4, P < 0.001) and stress (Δ − 2.4, P = 0.003) scores were observed in the HIIT group, while MICT only resulted in a reduction in stress scores (Δ − 2.9, P = 0.001). Reductions in anxiety scores were significantly higher in the HIIT group compared to the MICT group (β = − 2.24, P = 0.020). Both HIIT and MICT significantly improved multiple domain scores from the SF-36 and PCOSQ. This study highlights the potential of HIIT for improving mental health and HRQoL in overweight women with PCOS. HIIT may be a viable strategy to reduce symptoms of depression and anxiety in women with PCOS, however, large-scale studies are required to confirm these findings. Trial registration number: ACTRN12615000242527

Impact of Senescent Cell-Derived Extracellular Vesicles on Innate Immune Cell Function

Extracellular vesicles (EVs) are components of the senescence-associated secretory phenotype (SASP) that influence cellular functions via their cargo. Here, the interaction between EVs derived from senescent (SEVs) and non-senescent (N-SEVs) fibroblasts and the immune system is investigated. Via endocytosis, SEVs are phagocytosed by monocytes, neutrophils, and B cells. Studies with the monocytic THP-1 cell line find that pretreatment with SEVs results in a 32% (p &lt; 0.0001) and 66% (p &lt; 0.0001) increase in lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-α) production when compared to vehicle control or N-SEVs respectively. Interestingly, relative to vehicle control, THP-1 cells exposed to N-SEVs exhibit a 20% decrease in TNF-α secretion (p &lt; 0.05). RNA sequencing reveals significant differences in gene expression in THP-1 cells treated with SEVs or N-SEVs, with vesicle-mediated transport and cell cycle regulation pathways featuring predominantly with N-SEV treatment, while pathways relating to SLITS/ROBO signaling, cell metabolism, and cell cycle regulation are enriched in THP-1 cells treated with SEVs. Proteomic analysis also reveals significant differences between SEV and N-SEV cargo. These results demonstrate that phagocytes and B cells uptake SEVs and drive monocytes toward a more proinflammatory phenotype upon LPS stimulation. SEVs may therefore contribute to the more proinflammatory immune response seen with aging

The effects of two different doses of ultraviolet-A light exposure on nitric oxide metabolites and cardiorespiratory outcomes

PURPOSE: The present study investigated different doses of ultraviolet-A (UV-A) light on plasma nitric oxide metabolites and cardiorespiratory variables.METHODS: Ten healthy male participants completed three experimental conditions, 7 days apart. Participants were exposed to no light (CON); 10 J cm2 (15 min) of UV-A light (UVA10) and 20 J cm2 (30 min) of UV-A light (UVA20) in a randomized order. Plasma nitrite [NO2-] and nitrate [NO3-] concentrations, blood pressure (BP), and heart rate (HR) were recorded before, immediately after exposure and 30 min post-exposure. Whole body oxygen utilization ([Formula: see text]), resting metabolic rate (RMR) and skin temperature were recorded continuously.RESULTS: None of the measured parameters changed significantly during CON (all P?>?0.05). [Formula: see text] and RMR were significantly reduced immediately after UVA10 (P??0.05). Immediately after exposure to UVA20, plasma [NO2-] was higher (P?=?0.014) and [Formula: see text] and RMR tended to be lower compared to baseline (P?=?0.06). There were no differences in [NO2-] or [Formula: see text] at the 30 min time point in any condition. UV-A exposure did not alter systolic BP, diastolic BP or MAP (all P?>?0.05). UV-A light did not alter plasma [NO3-] at any time point (all P?>?0.05).CONCLUSIONS: This study demonstrates that a UV-A dose of 20 J cm2 is necessary to increase plasma [NO2-] although a smaller dose is capable of reducing [Formula: see text] and RMR at rest. Exposure to UV-A did not significantly reduce BP in this cohort of healthy adults. These data suggest that exposure to sunlight has a meaningful acute impact on metabolic function

Lower limb ischemic preconditioning combined with dietary nitrate supplementation does not influence time-trial performance in well-trained cyclists

OBJECTIVES: Dietary nitrate (NO3-) supplementation and ischaemic preconditioning (IPC) can independently improve exercise performance. The purpose of this study was to explore whether NO3- supplementation, ingested prior to an IPC protocol, could synergistically enhance parameters of exercise.DESIGN: Double-blind randomized crossover trial.METHODS: Ten competitive male cyclists (age 34±6years, body mass 78.9±4.9kg, V⋅O2peak 55±4 mLkgmin-1) completed an incremental exercise test followed by three cycling trials comprising a square-wave submaximal component and a 16.1km time-trial. Oxygen uptake (V⋅O2) and muscle oxygenation kinetics were measured throughout. The baseline (BASE) trial was conducted without any dietary intervention or IPC. In the remaining two trials, participants received 3×5min bouts of lower limb bilateral IPC prior to exercise. Participants ingested NO3--rich gel (NIT+IPC) 90min prior to testing in one trial and a low NO3- placebo in the other (PLA+IPC). Plasma NO3- and nitrite (NO2-) were measured immediately before and after application of IPC.RESULTS: Plasma [NO3-] and [NO2-] were higher before and after IPC in NIT+IPC compared to BASE (P0.4). Performance in the time-trial was similar between trials (BASE 1343±72s, PLA+IPC 1350±75s, NIT+IPC 1346±83s, P=0.98).CONCLUSIONS: Pre-exercise IPC did not improve sub-maximal exercise or performance measures, either alone or in combination with dietary NO3- supplementation

The effectiveness of high intensity intermittent training on metabolic, reproductive and mental health in women with polycystic ovary syndrome: study protocol for the iHIT- randomised controlled trial

Abstract Background Polycystic ovary syndrome (PCOS) is a reproductive-metabolic condition. Insulin resistance is a hallmark of PCOS and is related to increased hyperandrogenism that drives inherent metabolic, reproductive and psychological features of the syndrome. Insulin resistance in women with PCOS is managed by weight loss, lifestyle interventions (i.e. exercise, diet) and insulin-sensitising medications. This manuscript describes the protocol of our study evaluating the effectiveness of high intensity intermittent training (HIIT) or moderate intensity exercise on cardiometabolic, reproductive and mental health in overweight women with PCOS. Methods/design We will employ a three arm, parallel-group, randomised controlled trial recruiting 60 women diagnosed with PCOS, aged between 18 and 45 years and with a body mass index (BMI) greater than 25 kg/m2. Following screening and baseline testing, women will be randomised by simple randomisation procedure using computer generated sequence allocation to undergo one of two 12-week supervised interventions: either HIIT or moderate intensity exercise (standard supervised exercise), or to standard care [Con] (unsupervised lifestyle advice) at a 1:1:1 allocation ratio. The primary outcome for this trial is to measure the improvements in metabolic health; specifically changes in insulin sensitivity in response to different exercise intensities. Baseline and post-intervention testing include anthropometric measurements, cardiorespiratory fitness testing, reproductive hormone profiles (anti-müllerian hormone and steroid profiles), metabolic health, health-related quality of life and mental health questionnaires and objective and subjective lifestyle monitoring. Reporting of the study will follow the CONSORT statement. Discussion This trial aims to demonstrate the comparative efficacy and maintenance of different exercise intensities to advance the understanding of PCOS management and provide insight into the optimal exercise intensity for improved cardiometabolic outcomes. Secondary outcomes will include the impact of different exercise protocols on reproductive hormone profiles, mental health and health-related quality of life. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12615000242527. Registered on 17 March 2015

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly