Effects of Exercise on the Microvascular Response, Endothelial Health, and NO Bioavailability: A Systematic Review and Meta-Analysis of Preclinical Evidence
Pages 5-58
https://doi.org/10.22054/nass.2026.93581.1241
Ameer F ahem Hassan Al-Shaeef, Reza Farzizadeh, Farnaz Seifi-askishahr
Abstract Purpose: Mechanistic evidence from animal models is essential for understanding exercise-induced vascular adaptations, yet the translatability of these findings to clinical settings remains uncertain. This systematic review and meta-analysis quantified the effects of exercise training on endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) levels in animal models. Method: A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library (January 2000–September 2025) was done. The review protocol was registered with PROSPERO (CRD420251144669). A random-effects model (REML) was used for meta-analysis, and SYRCLE's Risk of Bias tool assessed study quality.
Results: Exercise training significantly increased eNOS levels (SMD = 0.99, 95% CI: 0.55–1.44, p < 0.001). In contrast, no significant effects were observed for NO (SMD = −1.26, 95% CI: −2.89–0.37, p = 0.13). Subgroup analyses showed that longer exercise duration (≥5 weeks; SMD = 2.25, p < 0.001) and specific modalities such as treadmill running (SMD = 1.92) and swimming (SMD = 4.59) were associated with substantially greater eNOS upregulation. Considerable heterogeneity was observed across most outcomes (I² > 85%). Conclusion: Exercise training effectively upregulates eNOS expression in animal models, particularly with interventions lasting five weeks or longer and with structured modalities like treadmill and swimming. However, the absence of significant effects on NO level, despite increased eNOS, reveals a translational gap that warrants further mechanistic investigation.
Effects of Short-Term Ziziphus jujuba Supplementation on Neutrophil Apoptotic Markers Following Circuit Resistance Exercise
Pages 59-84
https://doi.org/10.22054/nass.2026.94681.1248
Seyed Morteza Tayebi, mitra khademosharie, Hajar Nasiri, Fatemeh Chireh
Abstract Intense exercise such as circuit resistance training induces physiological stress and inflammation, potentially accelerating neutrophil apoptosis. This study investigated whether seven days of jujube supplementation could modify key apoptotic proteins in neutrophils following strenuous exercise. Fourteen healthy young men (mean age ~25 years) were randomly assigned to either a jujube supplementation group (0.5 g/kg/day) or a placebo group for seven days. After the supplementation period, all participants completed a circuit resistance protocol consisting of three rounds of nine exercises performed at 75% of one-repetition maximum. Blood samples were collected before exercise, immediately after, and two hours into recovery. Neutrophils were isolated, and the expression of Bcl-2, Mcl-1, Bid, and Caspase-9 proteins was measured using ELISA. Data were analyzed using repeated-measures ANOVA to evaluate time and group interactions. Significant time-by-group interactions were observed for Bcl-2 (p = 0.004) and Bid (p = 0.005). In the jujube group, Bcl-2 levels increased and Bid levels decreased during recovery compared with placebo. No significant changes were found for Mcl-1 (p = 0.112). Caspase-9 also showed no statistically significant differences, although it approached significance (p = 0.091). Short-term jujube supplementation may attenuate exercise-induced neutrophil apoptosis by enhancing anti-apoptotic signaling and reducing pro-apoptotic markers during recovery. However, given the small sample size, further studies with larger and more diverse populations are required to confirm these findings and clarify their physiological significance.
Enhancing Cardiorespiratory Function in Cancer Patients Through Exercise: A Systematic Review and Meta-Analysis
Pages 85-124
https://doi.org/10.22054/nass.2026.94873.1249
Jafar Sadiq Aribi, Farnaz Seifi-Asgshahr, Reza Farzizadeh
Abstract Purpose: Cancer treatments frequently reduce functional capacity and quality of life. The 6 Minute Walk Test (6MWT) is a valid measure of cardiorespiratory function, yet exercise responses across cancer types remain unclear.
Methods: Following PRISMA guidelines (PROSPERO: CRD420261466339), we systematically searched PubMed, Scopus, and Web of Science (inception–February 2026) for RCTs evaluating structured exercise effects on 6MWT in cancer patients. Random effects meta analysis (REML) calculated SMD with 95% CIs. Subgroup analyses examined cancer type, exercise modality, intensity, and duration. Publication bias was assessed using Egger's/Begg's tests and trim and fill.
Results: Seventeen studies (1,636 participants) were included. Exercise significantly improved 6MWT (SMD = 0.65, 95% CI: 0.07–1.19, p = 0.02), with substantial heterogeneity (I² = 93.0%). Cancer type significantly moderated effects (Q = 61.25, p = 0.001); breast cancer showed the greatest improvement (SMD = 1.28, p = 0.012), while prostate (SMD = 0.10, p = 0.870) and pancreatic cancer (SMD = 1.09, p = 0.205) were non significant. Exercise type also moderated outcomes (p < 0.001), with resistance training showing the largest effect (SMD = 5.75, p = 0.001, based on one study). Intensity moderated effects, but no intensity level alone reached significance.
Conclusion: Exercise improves cardiorespiratory function in cancer patients, but benefits vary by cancer type. Breast cancer patients respond best; prostate and pancreatic cancers may require optimized protocols. Long term programs (>12 weeks) yield more predictable outcomes. Prescriptions should be individualized.
Exercise-Induced Muscle Damage in Soccer: A Systematic Review and Meta-Analysis of the Moderating Roles of Age, Assessment Timing, and Cardiorespiratory Fitness
Pages 125-167
https://doi.org/10.22054/nass.2026.95317.1253
Murtadha Mohammed Radhi Al-Jazaieri, Ameneh PourRahim Ghouroghchi, Reza Farzizadeh
Abstract Purpose: Soccer players frequently experience exercise-induced muscle damage (EIMD) due to the high-intensity, eccentric demands of training and match-play. This systematic review and meta-analysis aimed to quantify the pooled effect of soccer-specific exercise training on serum CK levels and to examine the moderating roles of post-exercise assessment timing (≤ 25 vs. > 25 hours), participant age (≤ 20 vs. > 20 years), and VO₂max (≤ 57 vs. > 57 mL/kg/min).
Method: A systematic search of PubMed/MEDLINE, Scopus, and Web of Science was conducted from inception to 2026. Twenty-nine eligible studies were included. Random-effects meta-analyses and subgroup analyses were performed.
Results: Exercise training significantly elevated CK levels (SMD = 0.553, 95% CI: 0.249 to 0.856; P = 0.001), with substantial heterogeneity (I² = 71.07%; τ² = 0.558). Subgroup analyses revealed that CK elevations were significant when measured within 25 hours post-exercise (SMD = 0.65, 95% CI: 0.27 to 1.04; P = 0.001) but not beyond 25 hours (SMD = 0.47, 95% CI: −0.06 to 0.99; P = 0.082). Younger players (≤ 20 years) demonstrated substantially larger effects (SMD = 1.26, 95% CI: 0.28 to 2.24; P = 0.012) compared to older players (> 20 years; SMD = 0.42, 95% CI: 0.13 to 0.70; P = 0.004). VO₂max showed the strongest moderating trend, with higher VO₂max (> 57 mL/kg/min; k = 5) associated with markedly larger CK elevations (SMD = 2.42, 95% CI: 0.61 to 4.24; P = 0.009) compared to lower VO₂max (≤ 57 mL/kg/min; SMD = 0.44, 95% CI: 0.16 to 0.72; P = 0.002), although this between-subgroup difference did not reach statistical significance (Q = 4.63, P = 0.099).
Conclusion: Soccer-specific training induces moderate-to-large CK elevations. VO₂max emerged as the most promising moderating factor and warrants further investigation with larger, well-controlled studies.
The Role of High-Intensity Interval Training in Sleep Quality Regulation: Emphasis on Inflammation, Circadian Rhythms, and the Gut-Brain Axis
https://doi.org/10.22054/nass.2026.93535.1240
Mohamadreza Rabiee, Sajjad Mohamadyari, Hamid Omidi, MohamadAli Izadi
Abstract Background: Sleep quality is a key determinant of physical recovery, cognitive performance, and overall health. High-intensity interval training (HIIT) has emerged as a time-efficient exercise strategy with potential benefits for sleep regulation; however, the physiological mechanisms underlying these effects remain incompletely understood.
Objective: This narrative review aimed to critically evaluate the current evidence regarding the role of HIIT in sleep quality regulation, with particular emphasis on inflammation, circadian rhythms, and the gut-brain axis.
Methods: Literature published between 2000 and 2026 was identified through searches of PubMed, Scopus, Web of Science, and Google Scholar. Peer-reviewed original studies, randomized controlled trials, observational studies, systematic reviews, meta-analyses, and mechanistic reviews relevant to HIIT, sleep quality, inflammation, circadian biology, autonomic regulation, and the gut-brain axis were synthesized narratively.
Results: The available evidence was interpreted according to direct evidence, indirect physiological associations, and emerging mechanistic hypotheses. Overall, current evidence suggests that HIIT may support sleep quality primarily through improvements in cardiometabolic health, autonomic recovery, inflammatory regulation, and circadian entrainment. Gut-brain axis mechanisms remain biologically plausible but are supported mainly by emerging evidence, and direct causal evidence linking HIIT-induced microbiome adaptations to improvements in sleep quality remains limited.
Conclusion: HIIT appears to be a promising non-pharmacological strategy for improving sleep quality. However, the strength of evidence differs across the proposed mechanisms, and further well-designed longitudinal mechanistic studies integrating objective sleep assessment, inflammatory biomarkers, autonomic monitoring, and microbiome profiling are needed to clarify causal pathways and optimize exercise prescriptions for sleep health.
Neurophysiological Adaptations to Lifelong Endurance Training in Master Athletes: Mechanisms and Implications for Aging Performance
https://doi.org/10.22054/nass.2026.93910.1244
abdolrahman ghazzagh, ashkan koushki, hamid aghaalinejad
Abstract Aging induces neurophysiological changes across central and peripheral systems motor unit loss, fiber-type shifts, neuromuscular junction degeneration, and reduced spinal corticospinal excitability leading to declines in strength, power, motor control, and performance. To synthesize mechanisms of age related neuromuscular decline and evaluate how lifelong endurance training, using master athletes as a model, modifies these changes. Narrative review of studies on motor-unit remodeling, reflex pathway adaptations (H reflex, V wave), muscle contractile properties, and central drive in aging and with endurance training, with comparisons between master endurance athletes and sedentary peers. Lifelong endurance training preserves motor unit numbers, sustains spinal reflex excitability, and enhances fatigue resistance and submaximal performance. Nevertheless, it does not fully prevent age related losses in maximal strength, rate of force development, and fast twitch fiber function. These deficits respond best to resistance and power training that recruit high threshold motor units and augment central drive. Endurance training attenuates but does not abolish neuromuscular aging. Master athletes illustrate the protective role of chronic activity. The most effective strategy for functional capacity and fall-risk reduction in older adults is a multimodal program combining endurance with resistance, power, and neuromotor training to preserve strength, speed, and control.
FETAL ANDROGENS AND THEIR ASSOCIATION WITH PHYSICAL FITNESS IN RURAL BOYS: THE MEDIATING ROLES OF AGE, MATURITY, LEAN MASS, AND PHYSICAL ACTIVITY
https://doi.org/10.22054/nass.2026.94353.1246
Taher Afsharnezhad, Ali Asghar Marzi
Abstract Background: Previous research has reported an inverse association between the second-to-fourth digit ratio(2D:4D), a putative marker of prenatal androgen exposure, and physical fitness and athletic performance. However, the linearity of this relationship and the potential mediating roles of body composition and physical activity remain poorly understood in male youth.
Purpose:This study investigated the association between 2D:4D ratio and physical fitness in boys, while examining whether age, biological maturity, lean mass, and physical activity mediate this relationship.
Methods:A cross-sectional study was conducted in 218 healthy-boys aged 9–17 years. Participants underwent assessment of left- and right-hand 2D:4D ratios, physical activity, body composition (BMI and fat-free mass), and physical fitness components, including speed, agility, flexibility, and muscular strength. Pearson's correlation, curve estimation, stepwise multiple linear regression, and Sobel's test were used for statistical analyses(p
Applying aerobic exercise and physical activity as a therapeutic intervention after multiple sclerosis; review of applied methods and therapeutic interventions
https://doi.org/10.22054/nass.2026.95704.1255
Mohammad seyfi, Araz yahyaei, Mehdi Bayanirad, Seyedeh Saba Mohammadi khas
Abstract Multiple sclerosis (MS) is the most common neurodegenerative disease that causes disability in the central nervous system (CNS) as a result of destruction of myelin sheaths. Because myelinated CNS structures deteriorate, nerve signals are transmitted more slowly, leading to deficits in the function of targeted regions (mostly muscles). Physical training, especially aerobic exercise, because of its low-intensity nature, has been widely suggested to treat or control disease symptoms or progression. Here we provide a summary of the recent studies on the therapeutic effects of aerobic exercises on MS outcomes. Based on the reviewed literature, aerobic exercises, in any type, could improve various aspects of MS impairments such as the immune system, oxidative stress, cognition and behavior, fatigue, balance, quality of life… More studies could be done to clear precise effects of aerobic exercise on MS outcomes. The effect of non-aerobic exercise on MS patients can also be investigated in a more specialized manner.
Effects of 12 Weeks of Combined Aerobic–Resistance Exercise Snacks on Body Fat and Cardiometabolic Index in Sedentary Male University Students With Overweight or Obesity
https://doi.org/10.22054/nass.2026.95983.1257
Khalil allah Moonikh
Abstract Background: Evidence regarding the effects of exercise snacks on body composition and cardiometabolic health remains limited. This study examined 12 weeks of combined aerobic–resistance exercise snacks on body fat percentage (BF%) and cardiometabolic index (CMI) in sedentary male university students with overweight or obesity.
Methods: In this randomized controlled trial, 63 male university students volunteered and were screened; 36 eligible participants were randomly allocated to exercise-snack (n = 18) or control (n = 18) groups. The exercise group completed 15 sessions/week (75 min/week) for 12 weeks. Body weight, BMI, BF%, waist circumference (WC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and CMI were assessed before and after the intervention.
Results: Compared with controls, the exercise group had lower body weight (−5.66 kg), BMI (−1.78 kg/m²), BF% (−2.01 percentage points), and TG (−18.96 mg/dL), and higher HDL-C (+3.76 mg/dL; all P ≤ 0.001). At the overall mean baseline WC (98.62 cm) and CMI (1.955), estimated between-group differences were −5.88 cm and −0.49 units, respectively (both P < 0.001).
Conclusion: The intervention was associated with favorable short-term changes in body composition and selected lipid and cardiometabolic indices in the studied population. WC and CMI estimates were conditional on baseline values. The absence of quantified dietary intake, exercise adherence, and a conventional-training comparator precludes determining the independent contribution of the exercise-snack format. Longer controlled trials are needed to assess reproducibility, durability, and clinical relevance.
Effects of Traditional, Myo-Reps, and Combined Resistance Training on Muscle Thickness, Strength, BDNF, and CGRP in Resistance-Trained Men
https://doi.org/10.22054/nass.2026.95995.1258
Delaram Manjili, Ali Abbasi, Hamid Rajabi, Sadegh Amani-Shalamzari
Abstract Purpose: Myo-reps offers a time-efficient approach to resistance training, but its comparative effects on muscular adaptations remain unclear. Whether combining Myo-reps with traditional sets provides additional benefits for muscle thickness, strength, or exploratory circulating biomarkers of neurotrophic and neuromuscular responses warrants investigation. To compare the effects of eight weeks of Myo-reps, traditional, and combined resistance training on serum brain-derived neurotrophic factor (BDNF) and calcitonin gene-related peptide (CGRP), rectus femoris thickness, and lower-body strength in resistance-trained men.
Methods: Thirty-six men were randomized to traditional, Myo-reps, or combined training; 30 completed post-intervention assessments and were included in complete-case analyses. Training was performed three times weekly, with protocols matched for prescribed repetition count. Outcomes were assessed before and after training. Between-group effects were evaluated using baseline-adjusted ANCOVA.
Results: Training group affected rectus femoris thickness (p = 0.011, ηp² = 0.295), with greater adjusted post-intervention thickness after combined than traditional training (p = 0.010). Hack squat strength increased within all groups, but the adjusted group effect was nonsignificant (p = 0.513, ηp² = 0.050). BDNF and CGRP increased within the Myo-reps and combined groups; however, adjusted group effects were nonsignificant for BDNF (p = 0.762, ηp² = 0.021) and CGRP (p = 0.058, ηp² = 0.197).
Conclusion: Combined training produced greater localized hypertrophic adaptation than traditional training, whereas no protocol-specific effects on strength, BDNF, or CGRP were established.
Physical Activity and Exercise in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review of Hepatic, Metabolic, Anthropometric, and Cardiorespiratory Outcomes (2020–2026)
https://doi.org/10.22054/nass.2026.95663.1254
Bakhtyar Tartibian, Leila Fasihi, Rasoul Eslami
Abstract Objective: To synthesize evidence published from 2020 through August 2026 concerning the effects of physical activity and structured exercise on hepatic steatosis, liver enzymes, glucose-insulin homeostasis, lipid profile, body composition, inflammatory biomarkers, muscle-related outcomes, and cardiorespiratory fitness in adults with NAFLD/MASLD.
Methods: A PRISMA 2020-informed systematic-review framework was used. Eligible evidence included adult studies evaluating aerobic exercise, moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), resistance training, combined aerobic-resistance training, walking, home-based exercise, or hybrid programs. The review focused on liver fat/steatosis, ALT, AST, GGT, glucose, insulin, HOMA-IR, HbA1c, lipids, anthropometry, body composition, fitness, inflammation, and muscle outcomes. Because the manuscript source did not contain the final database export, screening log, or completed PRISMA counts, these values are deliberately not fabricated.
Results: The available evidence consistently supports exercise as a clinically relevant component of MASLD management. Prior meta-analytic evidence shows reductions in intrahepatic lipid and ALT. A 2024 network meta-analysis of 43 studies and 2,070 participants found modality-specific patterns, with aerobic plus resistance exercise ranking favorably for several lipid outcomes, aerobic exercise for ALT and HDL-C, and resistance exercise for AST.
Conclusion: Exercise should be considered a multidomain intervention rather than a strategy aimed solely at weight loss. No single modality is consistently superior for every outcome. HIIT may offer additional advantages for cardiorespiratory fitness, whereas MICT may provide an accessible hepatic benefit; resistance and combined training provide complementary metabolic and muscular effects.
