Dietary nitrate supplementation in cardiovascular health: An ergogenic aid or exercise therapeutic?

Oral consumption of inorganic nitrate, which is abundant in green leafy vegetables and roots, has been shown to increase circulating plasma nitrite concentration, which can be converted to nitric oxide in low oxygen conditions. The associated beneficial physiological effects include a reduction in blood pressure, modification of platelet aggregation, and increases in limb blood flow. There have been numerous studies of nitrate supplementation in healthy recreational and competitive athletes; however, the ergogenic benefits are currently unclear due to a variety of factors including small sample sizes, different dosing regimens, variable nitrate conversion rates, the heterogeneity of participants’ initial fitness levels, and the types of exercise tests used. In clinical populations, the study results seem more promising, particularly in patients with cardiovascular diseases who typically present with disruptions in the ability to transport oxygen from the atmosphere to working tissues and reduced exercise tolerance. Many of these disease-related, physiological maladaptations, including endothelial dysfunction, increased reactive oxygen species, reduced tissue perfusion, and muscle mitochondrial dysfunction, have been previously identified as potential targets for nitric oxide restorative effects. This review is the first of its kind to outline the current evidence for inorganic nitrate supplementation as a therapeutic intervention to restore exercise tolerance and improve quality of life in patients with cardiovascular diseases. We summarize the factors that appear to limit or maximize its effectiveness and present a case for why it may be more effective in patients with cardiovascular disease than as ergogenic aid in healthy populations

Intrinsic Plasmon-Phonon Interactions in Highly Doped Graphene: A Near-Field Imaging Study.

Author's accepted versionFinal version available from ACS via the DOI in this recordAs a two-dimensional semimetal, graphene offers clear advantages for plasmonic applications over conventional metals, such as stronger optical field confinement, in situ tunability, and relatively low intrinsic losses. However, the operational frequencies at which plasmons can be excited in graphene are limited by the Fermi energy EF, which in practice can be controlled electrostatically only up to a few tenths of an electronvolt. Higher Fermi energies open the door to novel plasmonic devices with unprecedented capabilities, particularly at mid-infrared and shorter-wave infrared frequencies. In addition, this grants us a better understanding of the interaction physics of intrinsic graphene phonons with graphene plasmons. Here, we present FeCl3-intercalated graphene as a new plasmonic material with high stability under environmental conditions and carrier concentrations corresponding to EF > 1 eV. Near-field imaging of this highly doped form of graphene allows us to characterize plasmons, including their corresponding lifetimes, over a broad frequency range. For bilayer graphene, in contrast to the monolayer system, a phonon-induced dipole moment results in increased plasmon damping around the intrinsic phonon frequency. Strong coupling between intrinsic graphene phonons and plasmons is found, supported by ab initio calculations of the coupling strength, which are in good agreement with the experimental data.FJGA and PA-G acknowledge support from the Spanish Ministry of Economy and Competitiveness through the national programs MAT2014-59096-P and FIS2014-60195-JIN, respectively. MFC and SR acknowledge support from EPSRC (Grant no. EP/J000396/1, 281 EP/K017160/1, EP/K010050/1, EPG036101/1, EP/M001024/1, EPM- 002438/1), from Royal Society International Exchanges Scheme 2012/R3 and 2013/R2 and from European Commission (FP7-ICT-2013-613024-GRASP). SD, DNB and MF acknowledge support of ONR N00014-15-1-2671. DNB is the Moore Investigator in Quantum Materials funded by the Gordon and Betty Moore Foundation’s EPiQS Initiative through Grant GBMF4533

Human skeletal muscle nitrate and nitrite in individuals with peripheral arterial disease: effect of inorganic nitrate supplementation and exercise

Skeletal muscle may act as a reservoir for N-oxides following inorganic nitrate supplementation. This idea is most intriguing in individuals with peripheral artery disease (PAD) who are unable to endogenously upregulate nitric oxide. This study analyzed plasma and skeletal muscle nitrate and nitrite concentrations along with exercise performance, prior to and following 12-weeks of exercise training combined with oral inorganic nitrate supplementation (EX+BR) or placebo (EX+PL) in participants with PAD. Non-supplemented, at baseline, there were no differences in plasma and muscle nitrate. For nitrite, muscle concentration was higher than plasma (+0.10 nmol.g−1). After 12 -weeks, acute oral nitrate increased both plasma and muscle nitrate (455.04 and 121.14 nmol.g−1, p < 0.01), which were correlated (r = 0.63, p < 0.01), plasma nitrate increase was greater than in muscle (p < 0.01). Nitrite increased in the plasma (1.01 nmol.g−1, p < 0.05) but not in the muscle (0.22 nmol.g−1) (p < 0.05 between compartments). Peak walk time (PWT) increased in both groups (PL + 257.6 s;BR + 315.0 s). Six-minute walk (6 MW) distance increased only in the (EX+BR) group (BR + 75.4 m). We report no substantial gradient of nitrate (or nitrite) from skeletal muscle to plasma, suggesting a lack of reservoir-like function in participants with PAD. Oral nitrate supplementation produced increases in skeletal muscle nitrate, but not skeletal muscle nitrite. The related changes in nitrate concentration between plasma and muscle suggests a potential for inter-compartmental nitrate “communication”. Skeletal muscle did not appear to play a role in within compartment nitrate reduction. Muscle nitrate and nitrite concentrations did not appear to contribute to exercise performance in patients with PAD

A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

Tendon Extracellular Matrix Damage, Degradation and Inflammation in Response to In Vitro Overload Exercise

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Wellcome Trust; Grant number: WT087112; Grant sponsor: Arthritis Research UK; Grant number: 2026

Frequency of Tongue Cleaning Impacts the Human Tongue Microbiome Composition and Enterosalivary Circulation of Nitrate

The oral microbiome has the potential to provide an important symbiotic function in human blood pressure physiology by contributing to the generation of nitric oxide (NO), an essential cardiovascular signaling molecule. NO is produced by the human body via conversion of arginine to NO by endogenous nitric oxide synthase (eNOS) but eNOS activity varies by subject. Oral microbial communities are proposed to supplement host NO production by reducing dietary nitrate to nitrite via bacterial nitrate reductases. Unreduced dietary nitrate is delivered to the oral cavity in saliva, a physiological process termed the enterosalivary circulation of nitrate. Previous studies demonstrated that disruption of enterosalivary circulation via use of oral antiseptics resulted in increases in systolic blood pressure. These previous studies did not include detailed information on the oral health of enrolled subjects. Using 16S rRNA gene sequencing and analysis, we determined whether introduction of chlorhexidine antiseptic mouthwash for 1 week was associated with changes in tongue bacterial communities and resting systolic blood pressure in healthy normotensive individuals with documented oral hygiene behaviors and free of oral disease. Tongue cleaning frequency was a predictor of chlorhexidine-induced changes in systolic blood pressure and tongue microbiome composition. Twice-daily chlorhexidine usage was associated with a significant increase in systolic blood pressure after 1 week of use and recovery from use resulted in an enrichment in nitrate-reducing bacteria on the tongue. Individuals with relatively high levels of bacterial nitrite reductases had lower resting systolic blood pressure. These results further support the concept of a symbiotic oral microbiome contributing to human health via the enterosalivary nitrate-nitrite-NO pathway. These data suggest that management of the tongue microbiome by regular cleaning together with adequate dietary intake of nitrate provide an opportunity for the improvement of resting systolic blood pressure

Pulmonary fibrosis induced by H5N1 viral infection in mice

<p>Abstract</p> <p>Background</p> <p>Inflammatory process results in lung injury that may lead to pulmonary fibrosis (PF). Here, we described PF in mice infected with H5N1 virus.</p> <p>Methods</p> <p>Eight-week-old BALB/c mice were inoculated intranasally with 1 × 10¹MID₅₀of A/Chicken/Hebei/108/2002(H5N1) viruses. Lung injury/fibrosis was evaluated by observation of hydroxyproline concentrations, lung indexes, and histopathology on days 7, 14, and 30 postinoculation.</p> <p>Results</p> <p>H5N1-inoculated mice presented two stages of pulmonary disease over a 30-d period after infection. At acute stage, infected-mice showed typical diffuse pneumonia with inflammatory cellular infiltration, alveolar and interstitial edema and hemorrhage on day 7 postinoculation. At restoration stage, most infected-mice developed PF of different severities on day 30 postinoculation, and 18% of the survived mice underwent severe interstitial and intra-alveolar fibrosis with thickened alveolar walls, collapsed alveoli and large fibrotic areas. The dramatically elevated hydroxyproline levels in H5N1-infected mice showed deposition of collagen in lungs, and confirmed fibrosis of lungs. The dry lung-to-body weight ratio was significantly increased in infected group, which might be associated with the formation of PF in H5N1-infected mice.</p> <p>Conclusion</p> <p>Our findings show that H5N1-infected mice develop the typical PF during restoration period, which will contribute to the investigation of fibrogenesis and potential therapeutic intervention in human H5N1 disease.</p

Digital self-management interventions for osteoarthritis: a systematic scoping review of intervention characteristics, adherence and attrition

BACKGROUND: Osteoarthritis (OA) is a chronic, progressive condition that can be effectively managed via conservative treatments including exercise, weight management and education. Offering these treatments contemporaneously and digitally may increase adherence and engagement due to the flexibility and cost-effectiveness of digital program delivery. The objective of this review was to summarise the characteristics of current digital self-management interventions for individuals with OA and synthesise adherence and attrition outcomes. METHODS: Electronic databases were searched for randomised controlled trials utilising digital self-management interventions in individuals with OA. Two reviewers independently screened the search results and extracted data relating to study characteristics, intervention characteristics, and adherence and dropout rates. RESULTS: Eleven studies were included in this review. Intervention length ranged from 6 weeks to 9 months. All interventions were designed for individuals with OA and mostwere multi-component and were constructed around physical activity. The reporting of intervention adherence varied greatly between studies and limited the ability to form conclusions regarding the impact of intervention characteristics. However, of the seven studies that quantified adherence, six reported adherence > 70%. Seven of the included studies reported attrition rates < 20%, with contact and support from researchers not appearing to influence adherence or attrition. CONCLUSIONS: Holistic digital interventions designed for a targeted condition are a promising approach for promoting high adherence and reducing attrition. Future studies should explore how adherence of digital interventions compares to face-to-face interventions and determine potential influencers of adherence. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13690-022-00854-x

Quantum surface-response of metals revealed by acoustic graphene plasmons

A quantitative understanding of the electromagnetic response of materials is essential for the precise engineering of maximal, versatile, and controllable light-matter interactions. Material surfaces, in particular, are prominent platforms for enhancing electromagnetic interactions and for tailoring chemical processes. However, at the deep nanoscale, the electromagnetic response of electron systems is significantly impacted by quantum surface-response at material interfaces, which is challenging to probe using standard optical techniques. Here, we show how ultraconfined acoustic graphene plasmons in graphene-dielectric-metal structures can be used to probe the quantum surface-response functions of nearby metals, here encoded through the so-called Feibelman d-parameters. Based on our theoretical formalism, we introduce a concrete proposal for experimentally inferring the low-frequency quantum response of metals from quantum shifts of the acoustic graphene plasmons dispersion, and demonstrate that the high field confinement of acoustic graphene plasmons can resolve intrinsically quantum mechanical electronic length-scales with subnanometer resolution. Our findings reveal a promising scheme to probe the quantum response of metals, and further suggest the utilization of acoustic graphene plasmons as plasmon rulers with angstrom-scale accuracy. Knowledge of the quantum response of materials is essential for designing light-matter interactions at the nanoscale. Here, the authors report a theory for understanding the impact of metallic quantum response on acoustic graphene plasmons and how such response could be inferred from measurements.N.A.M. is a VILLUM Investigator supported by VILLUM FONDEN (Grant No. 16498) and Independent Research Fund Denmark (Grant No. 7026-00117B). The Center for Nano Optics is financially supported by the University of Southern Denmark (SDU 2020 funding). The Center for Nanostructured Graphene (CNG) is sponsored by the Danish National Research Foundation (Project No. DNRF103). This work was partly supported by the Army Research Office through the Institute for Soldier Nanotechnologies under Contract No. W911NF-18-2-0048. N.M.R.P. acknowledges support from the European Commission through the project "Graphene-Driven Revolutions in ICT and Beyond" (No. 881603, Core 3), COMPETE 2020, PORTUGAL 2020, FEDER and the Portuguese Foundation for Science and Technology (FCT) through project POCI-01-0145-FEDER028114 and through the framework of the Strategic Financing UID/FIS/04650/2019. F.H. L.K. acknowledges financial support from the Government of Catalonia through the SGR grant and from the Spanish Ministry of Economy and Competitiveness (MINECO) through the Severo Ochoa Programme for Centres of Excellence in R&D (SEV-20150522), support by Fundacio Cellex Barcelona, Generalitat de Catalunya through the CERCA program, and the MINECO grants Plan Nacional (FIS2016-81044-P) and the Agency for Management of University and Research Grants (AGAUR) 2017 SGR 1656. Furthermore, the research leading to these results has received funding from the European Union's Horizon 2020 program under the Graphene Flagship Grant Agreements No. 785219 (Core 2) and no. 881603 (Core 3), and the Quantum Flagship Grant No. 820378. This work was also supported by the ERC TOPONANOP (Grant No. 726001)