Non-coding RNAs in exercise immunology: A systematic review.

Regular physical exercise has been recognized as a potent modulator of immune function, with its effects including enhanced immune surveillance, reduced inflammation, and improved overall health. While strong evidence exists that physical exercise affects the specific expression and activity of non-coding RNAs (ncRNAs) also involved in immune system regulation, heterogeneity in individual study designs and analyzed exercise protocols exists, and a condensed list of functional, exercise-dependent ncRNAs with known targets in the immune system is missing from the literature. A systematic review and qualitative analysis was used to identify and categorize ncRNAs participating in immune modulation by physical exercise. Two combined approaches were used: (a) a systematic literature search for "ncRNA and exercise immunology", (b) and a database search for microRNAs (miRNAs) (miRTarBase and DIANA-Tarbase v8) aligned with known target genes in the immune system based on the Reactome database, combined with a systematic literature search for "ncRNA and exercise". Literature searches were based on PubMed, Web of Science, and SPORTdiscus; and miRNA databases were filtered for targets validated by in vitro experimental data. Studies were eligible if they reported on exercise-based interventions in healthy humans. After duplicate removal, 95 studies were included reporting on 164 miRNAs, which were used for the qualitative synthesis. Six studies reporting on long-noncoding RNAs (lncRNAs) or circular RNAs were also identified. Results were analyzed using ordering tables that included exercise modality (endurance/ resistance exercise), acute or chronic interventions, as well as the consistency in reported change between studies. Evaluation criteria were defined as "validated" with 100% of ≥3 independent studies showing identical direction of regulation, "plausible" (≥80%), or "suggestive" (≥70%). For resistance exercise, upregulation of miR-206 was validated while downregulation of miR-133a appeared plausible. For endurance exercise, 15 miRNAs were categorized as validated, with 12 miRNAs being consistently elevated and 3 miRNAs being downregulated, most of them after acute exercise training. In conclusion, our approach provides evidence that miRNAs play a major role in exercise-induced effects on the innate and adaptive immune system by targeting different pathways affecting immune cell distribution, function, and trafficking as well as production of (anti-)inflammatory cytokines. miRNAs miR-15, miR-29c, miR-30a, miR-142/3, miR-181a, and miR-338 emerged as key players in mediating the immunomodulatory effects of exercise predominantly after acute bouts of endurance exercise.

Autonomic dysregulation in long-term patients suffering from Post-COVID-19 Syndrome assessed by heart rate variability.

Post-COVID-19 Syndrome (PCS) is a condition with multiple symptoms partly related to dysregulation of the autonomic nerve system. Assessment of heart rate variability (HRV) using 24 h Holter-ECG may serve as a surrogate to characterize cardiac autonomic activity. A prospective study including 103 PCS patients (time after infection = 252 days, age = 49.0 ± 11.3 years, 45.7% women) was performed and patients underwent detailed clinical screening, cardiopulmonary exercise testing, and 24 h Holter monitoring. Data of PCS patients was compared to 103 CAD patients and a healthy control group (n = 90). After correction for age and sex, frequency-related variables differed in PCS patients compared to controls including LF/HFpower, LF/HFnu, and LF/HF ratio (24 h; p ≤ 0.001). By contrast, these variables were largely comparable between PCS and CAD patients, while sympathetic activation was highest in PCS patients during the 24 h period. Overall, PCS patients showed disturbed diurnal adjustment of HRV, with impaired parasympathetic activity at night. Patients hospitalized during acute infection showed an even more pronounced overactivation of sympathetic activity compared to patients who underwent ambulant care. Our data demonstrate persistent HRV alterations in PCS patients with long-term symptom duration, suggesting a sustained impairment of sympathovagal balance. Moreover, sympathetic overstimulation and diminished parasympathetic response in long-term PCS patients are comparable to findings in CAD patients. Whether HRV variables have a prognostic value in PCS and/or might serve as biomarkers indicating a successful interventional approach warrants further longitudinal studies.

Medical Rehabilitation of Patients with Post-COVID-19 Syndrome-A Comparison of Aerobic Interval and Continuous Training.

INTRODUCTION: Post-COVID-19 syndrome (PCS) is a multisystemic disorder marked by impaired physical performance as one lead symptom. Since it has been suggested that endurance training as part of medical rehabilitation may be effective in improving physical performance capacity in PCS, this study aimed to compare different modes of aerobic endurance training. METHODS: A total of 110 PCS patients (49.3 ± 11.8 years; 38% women; time after infection = 260.2 ± 127.5 days) underwent detailed clinical screening including symptom-limited cardiopulmonary exercise testing at admission and after 4-6 weeks of inpatient medical rehabilitation. Questionnaires were used to assess disease perception. Patients performed controlled isocaloric cycle ergometer training (3-5 sessions/week; 18 min) as either continuous training (CT) at 50% of maximal workload or as interval training (IT; load = 60%, relief = 30%). Outcomes of PCS patients were compared to coronary artery disease patients (CAD; n = 96) to evaluate overall training effectiveness. RESULTS: Training participation was comparable between the groups, with no indication of training-specific exercise-induced fatigue. Overall, PCS patients improved significantly by a mean of 6.8 ± 12.1% for W at VT1; 3.1 ± 10.0% for VO2 at VT1; 5.5 ± 14.7% for O2 pulse at VT1; 7.5 ± 15.0% for W at VO2peak; 2.7 ± 11.0% for VO2peak and 4.6 ± 12.4% for O2 pulse at VO2peak (all p < 0.05) with no significant differences between groups (p > 0.05). Both groups showed reduced levels of fatigue, anxiety, and depression as well as improved quality of life and wellbeing (all p < 0.05). Compared to guideline-based cardiac rehabilitation, PCS patients showed a similar improvement in workload and oxygen uptake compared to CAD patients. CONCLUSION: PCS patients benefit from aerobic endurance training performed as moderate continuous or interval training as part of a medical rehabilitation program in terms of improved physical exercise capacity and disease perception. The results for PCS patients are comparable to the guideline-based rehabilitation of CAD patients.

Transcriptional Response of Two Brassica napus Cultivars to Short-Term Hypoxia in the Root Zone.

Waterlogging is one major stress for crops and causes multiple problems for plants, for example low gas diffusion, changes in redox potential and accumulation of toxic metabolites. Brassica napus is an important oil crop with high waterlogging sensitivity, which may cause severe yield losses. Its reactions to the stress are not fully understood. In this work the transcriptional response of rapeseed to one aspect of waterlogging, hypoxia in the root zone, was analyzed by RNAseq, including two rapeseed cultivars from different origin, Avatar from Europe and Zhongshuang 9 from Asia. Both cultivars showed a high number of differentially expressed genes in roots after 4 and 24 h of hypoxia. The response included many well-known hypoxia-induced genes such as genes coding for glycolytic and fermentative enzymes, and strongly resembled the hypoxia response of the model organism Arabidopsis thaliana. The carbohydrate status of roots, however, was minimally affected by root hypoxia, with a tendency of carbohydrate accumulation rather than a carbon starvation. Leaves did not respond to the root stress after a 24-h treatment. In agreement with the gene expression data, subsequent experiments with soil waterlogging for up to 14 days revealed no differences in response or tolerance to waterlogging between the two genotypes used in this study. Interestingly, using a 0.1% starch solution for waterlogging, which caused a lowered soil redox potential, resulted in much stronger effects of the stress treatment than using pure water suggesting a new screening method for rapeseed cultivars in future experiments.