Journal of Exercise & Organ Cross Talk

Abstract Hepatic gene expression of inflammatory and growth factors such as IL-8 and bFGF2 may be modulated in melanoma metastasis. Non-pharmacological interventions like exercise and anti-inflammatory supplements represent potential complementary strategies for modification. This study aimed to investigate the effects of aerobic exercise, pineapple extract supplementation, and their combination on the hepatic expression of CXCL2/IL-8 HOMOLOG and bFGF2 genes in a murine melanoma model. Melanoma-bearing mice were allocated into four groups (n=5 per group): Control, Aerobic Exercise, Pineapple Extract Supplement, and Aerobic Exercise + Pineapple Extract. After the intervention period, liver tissue was analyzed for CXCL2/IL-8 HOMOLOG and bFGF2 gene expression via one-way ANOVA and Tukey HSD test. Pearson correlation assessed the relationship between the two genes. A significant difference was observed in CXCL2/IL-8 HOMOLOG gene expression between groups (F=4.211, p=0.0239). Post hoc analysis revealed that only the combined Aerobic Exercise + Pineapple Extract group showed a significant decrease in hepatic CXCL2/IL-8 HOMOLOG compared to the Cancer Control group (p=0.0251). In contrast, no significant difference was found in bFGF2 gene expression across groups (F=1.425, p=0.2745). Correlation analysis indicated a significant negative relationship between CXCL2/IL-8 HOMOLOG and bFGF2 exclusively in the Cancer Control group (r = -0.948, p=0.013). The combination of aerobic exercise and pineapple extract supplementation significantly reduces hepatic CXCL2/IL-8 HOMOLOG expression in melanoma-bearing mice, suggesting a potential synergistic effect in modulating the hepatic inflammatory microenvironment. The distinct lack of effect on bFGF2 and the specific negative correlation in controls highlight pathway-selective responses.

Abstract Type 2 diabetes in older adults is characterized by chronic low-grade inflammation and oxidative stress, with elevated interleukin-1β (IL-1β) and reduced superoxide dismutase (SOD) activity playing central roles in disease progression.  This study aimed to investigate the independent and combined effects of eight weeks of moderate-intensity aerobic exercise and NBS superfood supplementation on serum IL-1β and SOD levels in elderly men with type 2 diabetes. Forty older men (aged 60–75 years) with type 2 diabetes were randomly allocated using stratified block randomization to four groups (n=10 each): control, exercise-only (TR), supplement-only (SUP), and exercise + supplement (TR+SUP). The exercise groups performed supervised cycling at 60–70% Wmax, 30 min/session, 3 sessions/week for 8 weeks. The supplementation groups received 10 g/day NBS superfood. Fasting serum IL-1β and SOD were measured before and 48 hours after the intervention using ELISA. Two-way repeated-measures ANOVA revealed significant time × group interactions for both IL-1β (p<0.001, η²p=0.372) and SOD (p<0.001, η²p=0.892). Post-hoc tests showed the greatest reductions in IL-1β and largest increases in SOD occurred in the TR+SUP group compared to all other groups (p<0.001), indicating a synergistic effect. Eight weeks of moderate-intensity aerobic exercise combined with NBS superfood supplementation exerts potent synergistic anti-inflammatory and antioxidant effects in older men with type 2 diabetes, suggesting a promising non-pharmacological strategy for managing chronic inflammation and oxidative stress.

Abstract Aerobic exercise has been proposed as a non-pharmacological intervention to modulate inflammatory gene expression, yet the molecular mechanisms remain incompletely understood. This study investigated the effects of a 12-week moderate-intensity aerobic exercise intervention on the mRNA expression levels of inflammation-related genes (TNF-α, IL-6, and IL-10) in peripheral blood mononuclear cells (PBMCs) of overweight individuals. Forty-five overweight adults (BMI 25-29.9 kg/m²) were randomly assigned to either an aerobic exercise group (n=30) or a sedentary control group (n=15). The exercise protocol consisted of supervised moderate-intensity aerobic training (60-75% HRmax) for 45-60 minutes, 5 days per week for 12 weeks. Blood samples were collected pre- and post- intervention for gene expression analysis using quantitative real-time PCR and protein quantification via ELISA. Following the 12-week intervention, the exercise group demonstrated significant reductions in TNF-α mRNA expression (−52.3%, p<0.001) and IL-6 expression (−47.8%, p<0.001) compared to baseline. Conversely, IL-10 expression increased significantly (+68.4%, p<0.001). Plasma protein concentrations paralleled these changes, with TNF-α decreasing from 8.6±2.1 to 4.9±1.3 pg/mL (p<0.001), IL-6 from 5.8±1.7 to 3.2±0.9 pg/mL (p<0.001), and IL-10 increasing from 3.1±0.8 to 5.6±1.2 pg/mL (p<0.001). Body mass index decreased significantly in the exercise group (−2.3 kg/m², p<0.001) with concurrent improvements in cardiorespiratory fitness (VO₂max increased by 18.7%, p<0.001). Moderate-intensity aerobic exercise effectively modulates the inflammatory gene expression profile in overweight individuals by downregulating pro-inflammatory genes (TNF-α and IL-6) and upregulating the anti- inflammatory gene (IL-10). These molecular adaptations may contribute to reduced inflammation and improved metabolic health in this population.

Abstract This study aimed to evaluate the individual and combined effects of aerobic training (AT) and pineapple supplementation (extract) on programmed cell death protein 1 (PD-1) gene expression within the tumor microenvironment and on systemic interleukin-10 (IL-10) levels in a murine melanoma model. Twenty C57BL/6 mice were randomly assigned into four groups (n=5 per group) following melanoma tumor induction: Tumor control, AT, Pineapple Supplement (PS), and AT+PS. The AT group underwent a structured aerobic training program, while the PS group received pineapple extract (300 mg/kg/day) via oral gavage for six weeks. Serum IL-10 concentrations were quantified by ELISA, and PD-1 mRNA expression in tumor tissue was analyzed using quantitative RT-PCR. All intervention groups—AT, PS, and their combination—resulted in a significant downregulation of PD-1 gene expression within the tumor compared to the control group (p < 0.05). In contrast, neither AT nor PS alone significantly altered systemic IL-10 levels. The combination therapy (AT+PS) produced the most pronounced suppression of PD-1 and was the only intervention to elicit a significant, though modest, reduction in serum IL-10. These findings indicate that the primary immunomodulatory effect of these interventions is localized to the tumor microenvironment and is largely independent of systemic IL-10 signaling. The synergistic combination of aerobic training and pineapple supplementation potently suppresses PD-1 gene expression, suggesting a promising, non-pharmacological strategy for enhancing anti-tumor immunity. Further investigation is required to confirm these effects at the protein level and to elucidate the underlying mechanisms.

Abstract The present study evaluates the effects of aerobic exercise and ethanolic bitter orange peel extract on the expression of cardioprotective genes in female rats fed a high-fat diet (HFD). From the Islamic Azad University's Central Tehran Branch animal facility, 30 adult female rats of the Wistar strain were randomly assigned to five groups (six rats per group): 1) normal diet control (ND-C), 2) HFD control (HFD-C), 3) HFD aerobic exercise (HFD-AE), 4) HFD ethanolic bitter orange peel extract (HFD-BP), and 5) HFD aerobic exercise and ethanolic bitter orange peel extract (HFD-AE-BP). A normal diet was supplemented with 20% palm oil, 1.5% cholesterol, and 0.25 cholic acid to induce obesity. Before the intervention, the subjects received a HFD for four weeks, then continued it for another four weeks during the intervention. During the four-week aerobic exercise protocol, treadmill running was performed at a moderate intensity. An ethanol extract of bitter orange peel was administered orally to rats at a dose of 100 milligrams per kilogram of body weight for four weeks. After euthanasia, left ventricle myocardium was collected for real-time PCR analysis of CTRP9, LKB1, and AMPK gene expression. In the HFD-C, CTRP9 (P=0.001), LKB1 (P=0.001), and AMPK (P=0.001) genes were significantly lower than in the ND-C. Aerobic exercise significantly increased their expression compared with the HFD-C (P=0.001). Comparing HFD-C with ethanolic bitter orange peel extract, ethanolic bitter orange peel extract increased gene expression significantly (P=0.001). This indicates that the simultaneous use of these two interventions was able to add up the effects of each and did not have a synergistic effect. However, since the magnitude of change when these two interventions were combined was greater than the effect of each alone, the combination of AE and BP was greater than the effect of each alone, suggesting that these two interventions may be used to mitigate cardiac complications under HFD conditions.

Abstract Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder associated with fat accumulation, sedentary lifestyle, and poor diet. This study examined the effects of aerobic exercise and mealworm protein supplementation on oxidative balance and the expression of FGF21 and mTOR genes in the soleus muscle of rats with NAFLD. Fifteen male Wistar rats (250 ± 50 g, aged 10–12 weeks) were randomly assigned to five groups: healthy control, fatty liver, fatty liver + supplement, fatty liver + exercise, and fatty liver + supplement + exercise. A high-fat diet was used to induce NAFLD. The exercise group performed moderate-intensity treadmill running (12–16 m/min) for eight weeks, five days per week. Mealworm protein (20 mg/kg) was administered via oral gavage. Liver and muscle tissues were analyzed using Real-Time PCR (FGF21, mTOR) and ELISA (TOS, TAC). Combined treatment significantly increased FGF21 expression (~130%; p = 0.022), reduced total oxidant status (~40%; p = 0.001), increased total antioxidant capacity (~45%; p = 0.009), and lowered SGPT and ALP levels (~32% and ~38%, respectively; p < 0.05). mTOR expression showed no significant change (p = 0.113), and the 18% SGOT reduction was not significant (p = 0.169). The combination had greater effects than either treatment alone. Aerobic exercise combined with mealworm protein supplementation improves oxidative balance and FGF21 expression in NAFLD. This integrative strategy may offer a novel therapeutic approach targeting liver-muscle metabolic interactions. Further human studies are recommended.

Abstract The aim of the present study is to investigate the effect of aerobic exercise and nano-curcumin supplementation on cardiac TGF-β1/TRAF6 and CTGF pathways in rat with brain tumors. Forty male Wistar rats were divided into 5 groups (n=8 in each) of healthy control, brain tumor, tumor + aerobic exercise (AE), tumor + nanocurcumin (N-CUR) and tumor+AE+N-CUR. Glioblastoma was injected into the rats in the frontal cortex. Nano curcumin supplement at the dose of 80 mg/kg was gavage for 4 weeks, 5 days a week. The training groups performed aerobic exercises on the treadmill for 4 weeks, 3 days a week at a speed of 18 meters per minute, for 25-40 minutes. At the end, the rats were sacrificed and TGF-β1, TRAF6, CTGF were analyzed from the myocardium by Real-time PCR method. Compared to the healthy control group, Tumor group significantly increased TGF-β1 mRNA and TRAF6 mRNA in the myocardium (p<0.05). Also, compared to the healthy control group, all tumor groups showed a significant increase in CTGF mRNA expression (p<0.05). In contrast to the Tumor group, the Tumor+AE and Tumor+AE+N-CUR groups showed a significant decrease in TGF-β1 mRNA at myocardium (p=0.0010 and p=0.0002, respectively). It seems that aerobic exercise or exercise with nano-curcumin supplement has better protective effects on the heart of tumor rats with downregulation of TGF-β1. It is suggested that different doses and various exercise modalities should be investigated to control cardiac fibrosis from the TGF-β1/TRAF6 and CTGF pathways.

Abstract Impaired cell internal settings and excessive proliferation causes the occurrence of diverse ranges of syndrom and diseases. The pathological stress underlying these conditions triggers persistent flux through multiple intracellular signaling pathways amongst MAPK/ERK as master regulator. Regarding the anti-inflammatory effects of muscle contraction induced myokines and nano-curcumin supplementation, we aimed to investigate the effects of aerobic training and nano-curcumin supplementation on RAS and ERK gene expression in rat muscle tissue. In this experimental study, 32 male wistar rats (aged 4-6 weeks, 130-150 g) were randomly assigned into 4 groups, including Control (C), Moderate Intensity Continious Training (MICT), Nano-Curcumin Supplementation (NCS) and Moderate Intensity Continious Training + Nano-curcumin (MICT+NCS). The training groups implemented the MICT protocol consisted of running at a velocity of 18-20 m/min, 5 days a week and for a total time of 4 weeks. The Supplement groups received 80 mg/kg/day through oral gavage. Regarding the results of one-way ANOVA, 4 weeks of moderate intensity aerobic exercise and Nano-curcumin supplementation led to a significant difference in the RAS (P=0.001) and ERK (P=0.01) gene expression levels in muscle tissue of rats among the study groups. Also, the results of the Bonferronie test showed that implementation of 4 weeks of MICT along with nano-curcumin supplementation alleviated the RAS/ERK gene expression levels, meanwhile nano-curcumin more efficiently down-regulated the pathway; suggesting that nano-curcumin can be an effective ergogenic aid for improving anti-inflmmatory properties through RAS/ERK signaling pathway.

Abstract The aim of this study was to considering the correlation between the muscle fibronectin type III domain-containing protein 5 (FNDC5), blood and heart level of Irisin in exercise-trained rats with Nano selenium supplementation after intraperitoneal injection of cigarette smoke extract induced chronic obstructive pulmonary disease (COPD). To this end, 49 male Wistar rats (8 weeks old) were divided into seven groups: control, SeNPs (2.5 mg/kg b.w by oral gavage, 3 days/week, 6 weeks), AIT (49 min/day, 5 days/week for 6 weeks, interval), SeNPs+AIT, CSE (150 µL by IP injection, 1 day/week for 6 weeks), CSE+AIT, and CSE+SeNPs+AIT. The results of the present study showed that CSE injection caused inflammation and damage to lung tissue, especially alveoli, compared to the healthy group. In other words, based on the histological examination of cigarette smoke extract, it was able to cause lung tissue damage similar to COPD, and doing exercise and taking nanoselenium antioxidant supplement could control these lung tissue damage. Pearson's correlation method was used to investigate the relationship between muscle FNDC5, serum and heart Irisin, and the results of this correlation were not significant in different groups (p>0.05). It seems that exercising and taking nanoselenium supplements can increase Irisin levels in serum and heart tissue by expanding muscle contraction and increasing muscle FNDC5. However, the relationship of this factor in muscle and heart crosstalk should be investigated more closely.

Abstract Performing aerobic exercise in different disease conditions can regulate cardiac homeostasis and reduce cardiac apoptosis caused by the disease. In brain cancer, other tissues, including cardiac tissue, can also be affected. Since exercise training causes organ crosstalk, in this study, the effects of aerobic exercise training (AET) on cardiac apoptosis in Glioblastoma multiforme (GBM) rats are evaluated. Twenty-four male Wistar rats were divided into 3 groups (n=8 in each) of healthy control, GBM, and GBM+AET. Glioblastoma was injected into the frontal cortex of rats. The training group (AET) performed aerobic exercises on the treadmill for 4 weeks, 3 days a week at a speed of 18 meters per minute, for 25-40 minutes. In the end, the rats were sacrificed and caspase-3 and caspase-7 were analyzed from the myocardium by Real-time PCR method. Considering H&E image, the GBM group showed necrosis and apoptosis in cardiac tissue compared to the healthy group. Compared to the healthy control group, GBM significantly increased caspase-3 and caspase-7 mRNA in the myocardium (p<0.05). However, in contrast to the GBM group, the GBM+AET showed a significant decrease in caspase-3 and caspase-7 mRNA at the myocardium (p<0.05). Since tumor formation in the body can affect other distant tissues in an endocrine manner, it is suggested to prioritize aerobic exercise to control the damage caused by GBM on heart tissue. However, more studies are needed, especially on human samples.

Abstract The purpose of this study was to determining the range of aerobic exercise on a treadmill for male Wistar rats at different ages. Twelve male Wistar rats were divide in three groups of immature, adults, and old (n= 4 in each). At first session, the rats began to run at a rate of 2 m/min to perform the fatigue test, and the treadmill speed was increased by 2 m/min every 2 minutes. This process of acceleration continued until the rats were no longer able to continue moving on the treadmill and became exhausted. Then, blood lactate of each subject measured immediately and their maximum speed was recorded. After 48 hours of recovery, animal performed maximum recorded speed on a treadmill in three 10-minute steps of 25%, 50% and 75%, respectively. Immediately after each percent blood lactate were measured and recorded. Immature rats at an average speed of 18 m/min were reached to their maximum speed with an average lactate concentration of 8±1.8 mmol/l. Adults rats at an average speed of 36 m/min were reached to their maximum speed with an average lactate concentration of 6.8±0.4 mmol/l. The old rats reached their maximum velocity with an average of 30 m/min with an average lactate concentration of 6.95±0.9 mmol/l. Therefore, it recommended that aerobic exercise in untrained rats start at a light speed, i.e. 25% of their maximum speed, which is lower than the lactate threshold, and gradually continue up to 50% of their maximum speed.

Abstract The aim of our study was to examine the effect of 12 weeks of moderate-intensity aerobic exercise on bone mineral density (BMD), lymphocyte alkaline phosphatase (ALP) mRNA expression, and biochemical markers of bone turnover in postmenopausal women (PMWs). Twenty-four healthy sedentary PMWs aged 45-70 years were randomly assigned to exercise (EX, n=12) and control (C, n=12) groups. The EX group performed walking/jogging (50-60min/day, 3days/week at 65%-70% HRmax reserve) for 12-week while the C group participated in no intervention and continued their normal lifestyle. The BMD and lymphocyte ALP mRNA were determined by DXA and qRT-PCR, respectively. After 12 weeks, the increase in the lymphocyte ALP mRNA expression and its serum (P=0.008 and P=0.001), PTH (P=0.001), Vit-D (P=0.002), and VO2max (P=0.001) were significantly higher in the EX group compared to the C group, whereas body fat was significantly decreased (P=0.028). Our study indicates that 12 weeks of moderate-intensity aerobic exercise intervention improves bone turnover by increasing the ALP mRNA expression, serum levels of PTH, ALP, and Vit-D which can lead to the prevention of aging-induced osteopenia among PMWs.