Bioinformatics Analysis Identifies Potential Ferroptosis Key Genes in the Pathogenesis of Pulmonary Fibrosis

Objective: Ferroptosis has an important role in developing pulmonary fibrosis. The present project aimed to identify and validate the potential ferroptosis-related genes in pulmonary fibrosis by bioinformatics analyses and experiments.Methods: First, the pulmonary fibrosis tissue sequencing data were obtained from Gene Expression Omnibus (GEO) and FerrDb databases. Bioinformatics methods were used to analyze the differentially expressed genes (DEGs) between the normal control group and the pulmonary fibrosis group and extract ferroptosis-related DEGs. Hub genes were screened by enrichment analysis, protein-protein interaction (PPI) analysis, and random forest algorithm. Finally, mouse pulmonary fibrosis model was made for performing an exercise intervention and the hub genes’ expression was verified through qRT-PCR.Results: 13 up-regulated genes and 7 down-regulated genes were identified as ferroptosis-related DEGs by comparing 103 lung tissues with idiopathic pulmonary fibrosis (IPF) and 103 normal lung tissues. PPI results indicated the interactions among these ferroptosis-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment and Genome-Ontology (GO) enrichment analyses showed that these ferroptosis-related genes involved in the organic anion transport, response to hypoxia, response to decrease oxygen level, HIF-1 signaling pathway, renal cell carcinoma, and arachidonic acid metabolism signaling pathway. The confirmed genes using PPI analysis and random forest algorithm included CAV1, NOS2, GDF15, HNF4A, and CDKN2A. qRT-PCR of the fibrotic lung tissues from the mouse model showed that the mRNA levels of NOS2 and GDF15 were up-regulated, while CAV1 and CDKN2A were down-regulated. Also, treadmill training led to an increased expression of CAV1 and CDKN2A and a decrease in the expression of NOS2 and GDF15.Conclusion: Using bioinformatics analysis, 20 potential genes were identified to be associated with ferroptosis in pulmonary fibrosis. CAV1, NOS2, GDF15, and CDKN2A were demonstrated to be influencing the development of pulmonary fibrosis by regulating ferroptosis. These findings suggested that, as an aerobic exercise treatment, treadmill training reduced ferroptosis in the pulmonary fibrosis tissues, and thus, reduces inflammation in the lungs. Aerobic exercise training initiate concomitantly with induction of pulmonary fibrosis reduces ferroptosis in lung. These results may develop our knowledge about pulmonary fibrosis and may contribute to its treatment.

Motor–Cognitive Treadmill Training With Virtual Reality in Parkinson’s Disease: The Effect of Training Duration

Treadmill training with virtual reality (TT + VR) has been shown to improve gait performance and to reduce fall risk in Parkinson’s disease (PD). However, there is no consensus on the optimal training duration. This study is a sub-study of the V-TIME randomized clinical trial (NCT01732653). In this study, we explored the effect of the duration of training based on the motor–cognitive interaction on motor and cognitive performance and on fall risk in subjects with PD. Patients in Hoehn and Yahr stages II–III, aged between 40 and 70 years, were included. In total, 96 patients with PD were assigned to 6 or 12 weeks of TT + VR intervention, and 77 patients completed the full protocol. Outcome measures for gait and cognitive performance were assessed at baseline, immediately after training, and at 1- and 6-month follow-up. The incident rate of falls in the 6-month pre-intervention was compared with that in the 6-month post-intervention. Dual-task gait performance (gait speed, gait speed variability and stride length under cognitive dual task and obstacle negotiation, and the leading foot clearance in obstacle negotiation) improved similarly in both groups with gains sustained at 6-month follow-up. A higher decrease in fall rate and fear of falling were observed in participants assigned to the 12-week intervention than the 6-week intervention. Improvements in cognitive functions (i.e., executive functions, visuospatial ability, and attention) were seen only in participants enrolled in 12-week training up to 1-month follow-up but vanished at the 6-month evaluation. Our results suggest that a longer TT + VR training leads to greater improvements in cognitive functions especially those directly addressed by the virtual environment.

Lower-Body Positive Pressure Treadmill Training for Pediatric Gait Disorders: A Scoping Review

The purpose of this scoping review was to examine the literature on the use of anti-gravity treadmills and its effects on lower-limb motor functions in children and adolescents with locomotor impairments. Method: Four databases (MEDLINE, CINAHL, Embase, Web of Science) were searched for articles from inception to August 2021. Inclusion criteria were: (1) experimental or quasi-experimental studies using anti-gravity training as the primary intervention; (2) studies conducted in pediatric participants; (3) articles reporting outcomes related to lower-limb functions; and (4) studies published in French or English. Results: Fifteen articles were included in the review. Studies included children and adolescents aged 4–18 years with locomotor impairments. Intervention duration ranged from 2 to 12 weeks, with 2–5 sessions per week. Included studies reported that anti-gravity training induces improvements in muscle strength, balance, spatiotemporal gait parameters, and walking endurance in children with locomotor impairments. Conclusion: This review provides relevant information about interventions, outcomes and limits associated with anti-gravity training in pediatrics. Overall, anti-gravity treadmill training could be viewed as a valuable training modality, specifically for children with cerebral palsy. However, a more precise and comprehensive description of anti-gravity training protocols would be useful.

Effects of virtual reality-based treadmill training on the balance and gait ability in patients after stroke

Gait and balance impairments contribute significantly to long-term disability after stroke. Modern concepts of stroke rehabilitation recommend a task-specific repetitive approach, such as using treadmill training. The purpose of this study was to investigate the effectiveness of using virtual reality-based treadmill training to improve balance and gait in subacute stroke patients. Twenty-two stroke patients were randomly stratified into two groups: the experimental (n = 11) and the control group (n = 11). Parameters associated with balance and gait were measured using the 6-minute walk test, the 10-meter walk test, the timed “up and go” test, the functional gait assessment, and the four square step test. Gait analysis using the zebris Rehawalk® treadmill system was also performed. Patients in the experimental group received virtual reality-based treadmill training five times a week for a period of four weeks, while those in the control group received treadmill training at the same frequency, duration, intensity, and structure, along with a progressively more difficult task demands. Significant improvements were observed in selected outcome measures in both groups after training. Patients in the experimental group experienced improvements in all of the spatiotemporal gait parameters, but there was a significant difference before and after training in duration of double support and lateral asymmetry. The findings of this pilot randomized controlled trial support the benefits of using a virtual reality-based treadmill training program to improve gait and balance in subacute stroke patients.

Treadmill Training Improves Aerobic Capacity in Aged Male Mice Compared to Voluntary Wheel Running

Preclinical exercise studies typically use two forms of exercise training protocols: 1) voluntary wheel running and 2) forced treadmill running. Previous work from our group clearly demonstrates that older (18-month-old) male mice do not voluntarily engage in wheel running, especially compared to younger males or female mice. Therefore, we implemented a forced exercise treadmill training protocol to determine if treadmill training was superior to wheel running in improving aerobic capacity in older male mice. Purpose To determine if a 3-week treadmill training protocol improved time to exhaustion (TTE) in older male mice. Methods 18-month-old male mice (n=5) were provided a running wheel in their individual cage for 2 weeks or underwent daily treadmill training (n=6) for 3 weeks with increasing speed/incline. At the end of the training period we assessed TTE. Results Older male mice that trained on the treadmill demonstrated higher TTE compared to wheel (1382 □ 32 seconds versus 500 □ 99 seconds, respectively). In addition, older male mice that trained on the treadmill improved on average ~8% in their TTE test. Conclusion A 3-week treadmill training protocol improves aerobic capacity in older male mice to a greater extent than voluntary wheel running. Ongoing experiments will utilize this training protocol to understand age-related declines in cardiorespiratory fitness, circadian rhythm, and to test exercise as an intervention in the aging population.

Lower Body Positive Pressure Treadmill Training for Pediatric Gait Disorders: A Scoping Review

The purpose of this scoping review was to examine the literature on the use of anti-gravity treadmill and its effects on lower limb motor functions in children and adolescents with locomotor impairments. Four databases (MEDLINE, CINAHL, Embase, Web of Science) were searched for articles from inception to August 2021. Inclusion criteria were: (1) experimental or quasi-experimental studies using the anti-gravity training as the primary intervention; (2) studies conducted in paediatricpediatric participants; (3) articles reporting outcomes related to the lower limb functions; and (4) studies published in French or English. Fifteen articles were included in the review. Studies included children and adolescents aged 4–18 years with locomotor impairments. The intervention duration was ranged from 2 and to 12 weeks, with 2-5 sessions per week. Included studies showed reported that anti-gravity training induces improvements in muscle strength, balance, spatiotemporal gait parameters, and walking endurance in children with locomotor impairments. This review provides relevant information about the modalities, outcomes and limits associated with the anti-gravity training protocol reported in the literature. Overall, the anti-gravity treadmill training could be viewed as a valuable training modality for children with cerebral palsy. However, more precise, and comprehensive description of anti-gravity rehabilitation protocols would be useful.

Changes in Gait Characteristics of Stroke Patients with Foot Drop after the Combination Treatment of Foot Drop Stimulator and Moving Treadmill Training

Objective. To study the changes in gait characteristics of stroke patients with foot drop after the combination treatment of foot drop stimulator and moving treadmill training and thus provide a basis for the improvement in a foot drop gait after stroke. Methods. Sixty patients with hemiplegia and foot drop caused by stroke were randomly divided into two groups of 30: the test group and the control group. Both groups received basic rehabilitation training. On this basis, the test group received the combination treatment of foot drop stimulator and moving treadmill training. The control group received foot drop stimulator training. Both groups received consecutive treatment for 3 weeks, five times a week, and every single time lasted for 30 minutes. Before and after the treatment, a gait watch three-dimensional gait analysis system was used to measure and record the maximum angles of flexion of the affected side’s hip, knee, and ankle; the pace; the step length asymmetry; the iEMG of the tibialis anterior muscle; the functional ambulation category; and Ashworth’s modified spasticity classification of the gastrocnemius. Results. After treatment, in the two groups, the maximum angles of flexion of the affected side’s hip, knee, and ankle improved, the pace increased, the step length asymmetry decreased, the iEMG of the tibialis anterior muscle increased, the functional ambulation category improved, and Ashworth’s modified spasticity classification of the gastrocnemius decreased, but the above changes in the test group were better than those in the control group. The difference is statistically significant ( p < 0.05 ). Conclusions. The combination treatment of the foot drop stimulator and moving treadmill can significantly improve stroke patients’ foot gait and promote the normalization of hip flexion, knee flexion, and ankle flexion. It can increase the pace, significantly reduce the step length asymmetry, reduce the muscle tone of the gastrocnemius, and improve walking function.