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 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 Recent studies highlight the role of molecular pathways, such as oxidative stress response and mitochondrial function, in COPD. This study explores the role of the PGC-1α gene, a key regulator of mitochondrial biogenesis and energy metabolism, using a rat model and bioinformatics analysis of human lung tissue samples. This study utilized a combined approach, analyzing gene expression in rat lung tissue alongside bioinformatics analysis of public human datasets. A total of 42 male Wistar rats were divided into seven groups, receiving treatments including cigarette smoke extract (CSE), nano-selenium (SeNPs), and aerobic interval training (AIT). PGC-1α expression levels were evaluated using quantitative Real-Time PCR (qRT-PCR) and analyzed using one-way ANOVA, followed by Dunnett’s post hoc test for multiple comparisons to determine significance across groups. The CSE+SeNPs+AIT group exhibited significantly higher PGC-1α expression compared to controls (p = 0.0289), indicating a potential protective role of SeNPs and exercise against oxidative stress. Bioinformatics analysis identified 250 differentially expressed genes (DEGs), with PGC-1α emerging as a critical hub gene associated with pathways like oxidative stress response and mitochondrial regulation. Protein-protein interaction (PPI) analysis further highlighted the centrality of PGC-1α in COPD pathophysiology. This study underscores the importance of PGC-1α in regulating mitochondrial function and oxidative stress in COPD. The findings suggest that PGC-1α could serve as a potential therapeutic target, offering insights into the development of interventions aimed at improving respiratory health in COPD patients. Future research should focus on validating these findings in clinical settings and exploring the therapeutic potential of PGC-1α modulation.

Abstract This study aims to investigate the effect of resistance-aerobic exercise and curcumin consumption on brain wnt/β-catenin expression and their correlation with muscle-enriched myokine musclin in rats with glioblastoma multiforme. Fourty male Wistar rats were used in this study. After getting familiarized with the research environment, the rats were randomly divided into five groups of eight: healthy control, tumor control, tumor + resistance-aerobic exercise, tumor + Nano-curcumin supplement, and tumor + aerobic-resistance exercise + Nano-curcumin supplement. For tumor induction, glioblastoma stereotaxic injection was utilized in the frontal cortex. The exercise training group did aerobic training and resistance training 3 days a week for 4 weeks. Nano curcumin supplement was gavage with a dose of 80 mg/kg for 4 weeks, 5 days a week. The brain histology changes of the groups with GBM injection confirmed brain tumor induction compared to the healthy control group (p<0.05). The expression of wnt/β-catenin genes in all tumor groups showed a significant increase compared to the healthy control group. Treatment with resistance-aerobic exercise and curcumin (especially the combination of both) revealed the greatest decrease in the expression of wnt/β-catenin genes compared to the tumor group. Wnt mRNA had a negative correlation with musclin mRNA in Tumor+N. cur group (r=-0.905, p=0.001). It seems that the use of nano supplements along with combined resistance-aerobic exercise can control the wnt/β-catenin signaling pathway in brain tumor tissue. In addition, the cross talk between muscle and brain should be more studied with considering different myokine.

Abstract Mechanical hindlimb suspension of lower extremities leads to prompt atrophy in rats' skeletal muscles. The present research was designed to study cross-section area (CSA) and the expression level of the genes ATF4, P53, MST1, and atrogin-1 in slow and fast skeletal muscles following mechanical hindlimb suspension. 20 male Wistar rats were assigned randomly in to two groups: control (Con) and hind-limb suspension (HU) (10 rats per each group). In HU group, tail suspension was designed for 14 constitutive days; however, animals in the control group passed a normal life.  The findings indicated that hind-limb suspension could relatively diminish CSA, myonuclei number per fiber and the weight of both soleus and EDL muscles. However, these reductions were not significant for EDL muscle. Furthermore, the expression level of the MST1, atrogin-1, ATF4, and p53 in soleus muscles elevated significantly. Moreover, the expression level of all four genes increased significantly in EDL muscle. Comparison of genes expression level between two soleus and EDL muscles showed that expression of MST1, ATF4, and p53 genes were higher in soleus than EDL, but it was not the case for atrogin-1 as its expression level was more in EDL compared to soleus. Our study provides novel evidence that immobilization of hind-limbs can induce a more powerful atrophic response in slow muscles in comparison to fast ones.