Kynurenine pathway dysregulation as a mechanistic link between cognitive impairment and brain damage: Implications for multiple sclerosis.

Cognitive impairment is a core symptom of multiple sclerosis (MS), resulting from inflammation-related brain damage and brain network dysfunction. Inflammation also causes dysregulation of the kynurenine pathway which is the primary route of tryptophan catabolism. Kynurenine pathway dysregulation is characterised by a shift in concentrations of tryptophan catabolites, also referred to as kynurenines.

Neutrophil but not lymphocyte response to matched interval and continuous running differs between protocols and sex.

When considering the acute effects of different modalities of endurance training on cellular immune components, the matching of duration and mean intensity and the consideration of sex-dependent differences have received less attention so far. The aim of the study was to compare the effects of interval running (IR) vs. continuous running (CR) on circulating immune cells and cellular immune inflammation markers.

Baseline Inflammation but not Exercise Modality Impacts Exercise-induced Kynurenine Pathway Modulation in Persons With Multiple Sclerosis: Secondary Results From a Randomized Controlled Trial.

Background: The kynurenine pathway (KP) is an important hub in neuroimmune crosstalk that is dysregulated in persons with multiple sclerosis (pwMS) and modulated by exercise in a modality-specific manner.

Objectives: To compare changes in the KP metabolite profile of pwMS (1) following combined treatments including either high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) during a 3-week multimodal rehabilitation, (2) to evaluate exercise response in relation to baseline systemic inflammation, and (3) to investigate associations of kynurenines with physical capacity and clinical outcomes.

Methods: For this secondary analysis of a randomized controlled trial, serum concentrations of kynurenines at baseline and after 3 weeks were determined using targeted metabolomics (LC-MS/MS).

Acute exercise boosts NAD metabolism of human peripheral blood mononuclear cells.

Nicotinamide adenine dinucleotide (NAD) coenzymes are the central electron carriers in biological energy metabolism. Low NAD levels are proposed as a hallmark of ageing and several diseases, which has given rise to therapeutic strategies that aim to tackle these conditions by boosting NAD levels. As a lifestyle factor with preventive and therapeutic effects, exercise increases NAD levels across various tissues, but so far human trials are mostly focused on skeletal muscle.

Predictors of six-month change in health-related quality of life in people with multiple sclerosis: A secondary data analysis of a randomized controlled trial.

Background: Symptomatic treatment in people with multiple sclerosis (pwMS) requires multidisciplinary rehabilitation to alleviate disease progression and increasing health-related quality of life (HRQoL). However, the participant- and disease-specific factors that predict sustained improvement in HRQoL in pwMS undergoing inpatient rehabilitation remain unclear. Identifying these factors can help individually tailor inpatient rehabilitation programmes.

Acute exercise activates the AHR in peripheral blood mononuclear cells in an intensity-dependent manner.

The kynurenine pathway (KP) of tryptophan degradation generates several metabolites such as kynurenine (KYN) or kynurenic acid (KA) that serve as endogenous ligands of the aryl hydrocarbon receptor (AHR). Due to its distinct biological roles particularly modulating the immune system, the AHR is a current therapeutic target across different inflammation-related diseases. Here, we show an acute exercise-induced increase in AHR ligand availability on a systemic level and a kynurenine pathway activation in peripheral blood mononuclear cells (PBMCs).

Kinetics of Immune Cell Mobilization during Acute Aerobic Exercise in Healthy Adults.

While pre-post differences in immune cell mobilization after acute aerobic exercise are well investigated, less is known about when and to what extent immune cells are mobilized during acute aerobic exercise. This experimental trial aimed to investigate the detailed kinetics of circulating immune cells in twelve healthy adults (n=6 females) who completed a 40-min aerobic exercise bout at 60% of the participants' V̇O2 on a bicycle ergometer. Cellular inflammation markers and sex-dependent differences in circulating immune cells were analyzed.

Molecular insights of exercise therapy in disease prevention and treatment.

Despite substantial evidence emphasizing the pleiotropic benefits of exercise for the prevention and treatment of various diseases, the underlying biological mechanisms have not been fully elucidated. Several exercise benefits have been attributed to signaling molecules that are released in response to exercise by different tissues such as skeletal muscle, cardiac muscle, adipose, and liver tissue. These signaling molecules, which are collectively termed exerkines, form a heterogenous group of bioactive substances, mediating inter-organ crosstalk as well as structural and functional tissue adaption.

Impact of exercise on markers of B cell-related immunity: A systematic review.

Background: B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins. Exercise alters B cell counts and immunoglobulin levels, but evidence-based conclusions on potential benefits for adaptive immunity are lacking. This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells, immunoglobulins, and markers of secretory immunity in human biofluids.

Physical activity is related to disease severity and fatigue, but not to relapse rate in persons with relapsing remitting multiple sclerosis - a self-reported questionnaire based study.

Introduction: Based on theoretical models, physical activity has been introduced as a promoting method to mitigate the disease severity, fatigue and relapse rate in multiple sclerosis. The primary objective of the study was to investigate the relation between self-reported physical activity level and disease severity, fatigue and relapse rate in persons with relapsing remitting multiple sclerosis (RRMS).

Methods: A survey was offered to persons with RRMS from March 2019 to August 2021 ( = 253).

Effects of inpatient energy management education and high-intensity interval training on health-related quality of life in persons with multiple sclerosis: A randomized controlled superiority trial with six-month follow-up.

Background: Fatigue is one of the most frequent symptoms in persons with multiple sclerosis (pwMS) and impacts health-related quality of life (HRQoL). A multidisciplinary rehabilitation approach is recommended for the treatment of fatigue in pwMS. However, high-quality evidence exists only for unimodal interventions, such as physical therapies/exercise or energy/fatigue management programmes.

12-week combined strength and endurance exercise attenuates CD8 T-cell differentiation and affects the kynurenine pathway in the elderly: a randomized controlled trial.

Background: Age-related accumulation of highly differentiated CD8 effector memory re-expressing CD45RA (EMRA) T-cells and disruption of the kynurenine (KYN) pathway are associated with chronic inflammation and the development of insulin resistance. In this study the aim was to investigate the effects of 12-week combined strength and endurance exercise on CD8 T-cell differentiation and KYN pathway metabolites. Ninety-six elderly subjects (f/m, aged 50-70) were randomized to a control (CON) or exercise (EX) group.

Cycling in primary progressive multiple sclerosis (CYPRO): study protocol for a randomized controlled superiority trial evaluating the effects of high-intensity interval training in persons with primary progressive multiple sclerosis.

Background: Primary progressive multiple sclerosis (PPMS) is the least prevalent multiple sclerosis (MS) phenotype. For persons with PPMS (pwPPMS), pharmacological treatment options are limited. As a complementary non-pharmacological treatment, endurance training improves the health-related quality of life (HRQoL), numerous MS symptoms, and MS-related performance impediments.

The serum kynurenine pathway metabolic profile is associated with overweight and obesity in multiple sclerosis.

Background: Overweight and obesity increase multiple sclerosis (MS) susceptibility, disease severity, and disability progression. Kynurenine pathway (KP) dysregulation is present in overweight and obesity, and in MS. Since the effect of overweight and obesity on KP dysregulation in persons with MS (pwMS) remains to be established, this study primarily aims to explore the effect of overweight and obesity on the serum KP metabolic profile in pwMS.

Tissue-specific effects of exercise as NAD -boosting strategy: Current knowledge and future perspectives.

Nicotinamide adenine dinucleotide (NAD ) is an evolutionarily highly conserved coenzyme with multi-faceted cell functions, including energy metabolism, molecular signaling processes, epigenetic regulation, and DNA repair. Since the discovery that lower NAD levels are a shared characteristic of various diseases and aging per se, several NAD -boosting strategies have emerged. Other than pharmacological and nutritional approaches, exercise is thought to restore NAD homeostasis through metabolic adaption to chronically recurring states of increased energy demand.

Cellular Integrative Immune Markers in Elite Athletes.

The integrative immune markers , and (SII) are established markers in clinical patient care. Adoption of these markers in elite athletics might prove beneficial for monitoring training and health. Blood samples of 195 healthy national Olympic squad athletes were collected before a graded bicycle-ergometric exercise test until complete exhaustion.

Effect of sleep and fatigue on cardiovascular performance in young, healthy subjects.

Physical performance could be negatively affected by sleep deficiency and fatigue. The present study assesses the role of sleep quality, fatigue and motivation on cardiovascular performance (VOpeak, Wmax, and HRmax) in a sample of active young subjects. The current study is a cross-sectional design.

Distinct distribution patterns of exercise-induced natural killer cell mobilization into the circulation and tumor tissue of patients with prostate cancer.

The mobilization and activation of natural killer (NK) cells have been proposed as key mechanisms promoting anti-oncogenic effects of physical exercise. Although mouse models have proven that physical exercise recruits NK cells to tumor tissue and inhibits tumor growth, this preclinical finding has not been transferred to the clinical setting yet. In this first-in-human study, we found that physical exercise mobilizes and redistributes NK cells, especially those with a cytotoxic phenotype, in line with preclinical models.

Fitness, physical activity, and exercise in multiple sclerosis: a systematic review on current evidence for interactions with disease activity and progression.

Background: A moderate to high level of physical activity, including regular exercise, represents an established behavioral and rehabilitative approach for persons with multiple sclerosis (pwMS). Although being increasingly proposed to limit disease activity and progression, high-quality evidence is lacking.

Objective: The objective of the study is to provide valuable information for MS clinicians and researchers by systematically evaluating the current state of evidence (i) whether exercise interventions affect established clinical measures of disease activity and progression in pwMS (i.

The aerobic capacity - fatigue relationship in persons with Multiple Sclerosis is not reproducible in a pooled analysis of two randomized controlled trials.

Background: Fatigue is one of the most frequent symptoms of persons with Multiple Sclerosis (pwMS) but has limited treatment options. Aerobic capacity and endurance training have been discussed as relevant factors to improve fatigue. However, over the last decades, results have been equivocal.

Exercise reduces systemic immune inflammation index (SII) in childhood cancer patients.

While exercise and physical activity have been suggested to reduce mortality and symptoms in cancer, knowledge on these associations in patients with childhood cancer (CCPs) is sparse. Anti-inflammatory properties of exercise might mediate these beneficial effects. We investigated the influence of exercise on the inflammation markers neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic-immune-inflammation index (SII) and associations to patient-reported-outcomes in CCPs in a randomized-controlled trial.

How acute physical and psychological stress differentially influence the kynurenine pathway: A randomized cross-over trial.

Psychological stress is associated with the pathogenesis of several neuropsychiatric disorders. In contrast, physical stress, as provoked by exercise, counteracts symptoms and potentially also disease progression. The kynurenine pathway, which is imbalanced in neuropsychiatric disorders, responds to both psychological and physical stress.

Systematic Review of Exercise Studies in Persons with Multiple Sclerosis: Exploring the Quality of Interventions According to the Principles of Exercise Training.

Introduction: The objective of this systematic review is to explore the application and reporting of (i) the principles of exercise training in exercise trials, (ii) the components of exercise prescription, and (iii) the adherence towards the prescribed programmes in randomised controlled trials (RCTs) in persons with multiple sclerosis (pwMS).

Methods: The MEDLINE, CINAHL, SPORTDiscus, PubMed and Embase electronic databases were searched from 1 January 2000 to 16 October 2020. RCTs comprising at least 3 weeks of aerobic and/or resistance exercise intervention in pwMS that reported at least one physiological outcome and were published in peer-reviewed journals were eligible for inclusion.