Swimming exercise alleviates pathological bone features in curdlan-injected SKG mice by inducing irisin expression.

This study assessed the therapeutic potential of swimming exercise in the curdlan-injected SKG mouse model and investigated the modulatory effects of irisin on inflammation. Curdlan-injected SKG were randomly assigned to either a home-cage group or a swimming group for 6 weeks. Changes in clinical arthritis scores and ankle thickness were measured weekly. Post-swimming program, mice were anesthetized for collection of vastus lateralis muscle and blood, which was followed by histological analysis, micro-CT imaging of the ankle joints, and the measurement of pro-inflammatory cytokines and irisin levels. Additionally, curdlan-injected SKG mice were intravenously injected with recombinant irisin protein and observed. Finally, serum levels of irisin in healthy control and ankylosing spondylitis (AS) patient groups were measured by ELISA. The swimming group of curdlan-injected SKG mice exhibited significant improvements in arthritis and enthesitis compared to the home-cage group. In particular, micro-CT and histological analyses revealed a notable reduction in pathological bone features in the swimming group compared to the home-cage group. Muscle endurance was also enhanced in the swimming group compared to the home-cage group, as determined by the wire-hanging test. Intriguingly, irisin levels not only were statistically increased in the swimming group but, also, TNF-α, IL-1ß, and IL-6 levels were decreased. Additionally, injection of irisin protein slightly attenuated both arthritis and enthesitis in curdlan-injected SKG mice. Meanwhile, irisin serum levels were declined in AS patients. Overall, we found that swimming exercise attenuated pathological bone features in an AS animal model, potentially mediated by increased irisin serum levels with associated anti-inflammatory effects.

The Effect of Chronic Swimming Exercise and Vitamin E Supplementation on Bone Element Metabolism in Epileptic Rats.

Introduction: This study aimed to investigate the effects of chronic swimming exercise and vitamin E administration on elemental levels in the bone tissue of epileptic rats. Methods: Forty-eight rats were divided into six groups: Control, Swimming, Swimming + vitamin E, Swimming + Epilepsy, Swimming + Epilepsy + vitamin E, and Epilepsy. Vitamin E was administered to the animals chronically by gavage at a dose of 500 mg/kg every other day for 3 months. Epileptiform activity was induced with penicillin in animals 24 hours after the last vitamin E intake. The exercise program consisted of daily 30-minute swimming sessions. At the end of the treatment period, the levels of calcium, chromium, copper, iron, magnesium, manganese, lead, and zinc (µg/gram tissue) in bone tissue samples were measured using an atomic emission device. Results: The results showed that all epileptic groups had significantly lower bone chromium levels compared to the control groups (p<0.05). The epileptic, and epileptic swimming groups had the lowest levels of bone calcium, magnesium, and zinc (p<0.05). Vitamin E administration resulted in a significant increase in bone calcium, magnesium, and zinc levels in the epileptic swimming group with vitamin E compared to the epileptic and epileptic swimming groups. (p<0.05). Conclusion: The findings of the study show that the administration of vitamin E improves calcium, magnesium, and zinc metabolism in the deteriorated bone tissue of the epileptic rat model.

Pulmo-protection of long-term swimming exercise via improving insulin sensitivity in monocrotaline-induced pulmonary hypertensive rats.

Exercise has been recognized as an effective intervention in the treatment of pulmonary arterial hypertension (PAH), supported by numerous studies. However, the precise effects of exercise on pulmonary function remain to be fully elucidated. In this study, using a rat model of swimming exercise training and monocrotaline-induced PAH, we aimed to explore its impact on pulmonary morphology and function. Our investigations revealed that MCT-treated rats exhibited augmented mean pulmonary arterial pressure (MPAP) and pulmonary vascular remodeling, which can be attenuated by 4 weeks of swimming exercise training (60 min/day, 5 days/week). Notably, MCT-treated rats showed impaired pulmonary function, as manifested by decreased tidal volume and dynamic compliance, which were reversed by exercise training. Assessment of pulmonary substrate in PAH rats indicated a prominent pro-inflammatory substrate, evidenced by macrophage accumulation through quantitative immunohistological analysis of macrophage-like cell expression (CD68), and extracellular matrix remodeling, evaluated by Masson staining. Importantly, both the pro-inflammatory substrate and extracellular matrix remodeling were ameliorated by swimming exercise training. Additionally, serum biochemical analysis demonstrated elevated levels of low-density lipoprotein cholesterol and Apolipoprotein B following MCT treatment, which were reduced with exercise intervention. Moreover, exercise enhanced systemic insulin sensitivity in both MCT-treated and untreated rats. Notably, MCT and exercise treatment both decreased fasting blood glucose (FBG) levels in rats, whereas exercise training reinstated FBG levels to normal in MCT-treated rats. In summary, our study suggests that swimming exercise confers a pulmonary protective effect in MCT-induced PAH rats, highlighting the potential importance of exercise-based rehabilitation in the management of PAH.

Beneficial effects of swimming and pomegranate juice in rats with hypertension: A possible role of serum adropin.

Hypertension, characterized by persistent and uncontrolled high blood pressure, is one of the most common significant causes of mortality worldwide. Lifestyle modifications such as exercise and antioxidant intake have showed beneficial effects on hypertensive conditions. Adropin and endothelin-1 (ET-1) have important vasoregulatory functions in the endothelium. However, the underlying mechanisms linking exercise- and/or antioxidant intake-mediated improvement of hypertension are not fully understood. In this study, it was hypothesized that swimming exercise and pomegranate juice (PJ) (as an antioxidant) administration might have protective effects on hypertension development and possible involvements of serum adropin and ET-1. To test the hypothesis, the rats with hypertension, induced by Nω-nitro-L-arginine methyl ester hydrochloride, were subjected to swimming exercise and received PJ for 8 weeks. Weekly systolic and diastolic pressures, serum concentrations of adropin and ET-1, and oxidant/antioxidant parameters in various tissues were measured. The obtained data show that swimming exercise leads to complete protection against hypertension within the 8-week duration, whereas the PJ administration causes an ameliorative effect. In addition, the combination of swimming exercise and PJ administration do not have additive effects in protection against hypertension. Notably, the 8-week swimming exercise restores the diminished serum adropin concentration in rats with hypertension to the control level. Serum adropin significantly correlated with systolic and diastolic pressures, depending on swimming exercise, but not PJ administration. Serum ET-1 concentration inconsistently fluctuates in response to Nω-nitro-L-arginine methyl ester hydrochloride, swimming exercise, and PJ intake. In addition, swimming exercise and/or PJ administration lead to a complete normalization in liver malondialdehyde concentrations of rats with hypertension, whereas these interventions cause slight or no improvements in superoxide dismutase, catalase, and glutathione in the heart, liver, and kidney. In conclusion, 8-week swimming exercise modulates hypertension, possibly by influencing adropin concentration and oxidative stress.

Swimming exercise reverses transcriptomic changes in aging mouse lens.

BACKGROUND: The benefits of physical activity for the overall well-being of elderly individuals are well-established, the precise mechanisms through which exercise improves pathological changes in the aging lens have yet to be fully understood. METHODS: 3-month-old C57BL/6J mice comprised young sedentary (YS) group, while aging mice (18-month-old) were divided into aging sedentary (AS) group and aging exercising (AE) group. Mice in AE groups underwent sequential stages of swimming exercise. H&E staining was employed to observe alterations in lens morphology. RNA-seq analysis was utilized to examine transcriptomic changes. Furthermore, qPCR and immunohistochemistry were employed for validation of the results. RESULTS: AE group showed alleviation of histopathological aging changes in AS group. By GSEA analysis of the transcriptomic changes, swimming exercise significantly downregulated approximately half of the pathways that underwent alterations upon aging, where notable improvements were 'calcium signaling pathway', 'neuroactive ligand receptor interaction' and 'cell adhesion molecules'. Furthermore, we revealed a total of 92 differentially expressed genes between the YS and AS groups, of which 10 genes were observed to be mitigated by swimming exercise. The result of qPCR was in consistent with the transcriptome data. We conducted immunohistochemical analysis on Ciart, which was of particular interest due to its dual association as a common aging gene and its significant responsiveness to exercise. The Protein-protein Interaction network of Ciart showed the involvement of the regulation of Rorb and Sptbn5 during the process. CONCLUSION: The known benefits of exercise could extend to the aging lens and support further investigation into the specific roles of Ciart-related pathways in aging lens.

Effects of Exercise Training and L-Arginine Loaded Chitosan Nanoparticles on Hippocampus Histopathology, ß-Secretase Enzyme Function, APP, Tau, Iba1and APOE-4 mRNA in Aging Rats.

The objective of this study was to evaluate the combined and independent effects of exercise training and L-Arginine loaded chitosan nanoparticles (LA CNPs) supplementation on hippocampal Tau, App, Iba1, and ApoE gene expression, oxidative stress, ß-secretase enzyme activity, and hippocampus histopathology in aging rats. Thirty-five male Wistar rats were randomly assigned to five groups (n = 7 in each): Young (8 weeks old), Old (20 months old), old + L-arginine supplementation (Old Sup), old + exercise (Old Exe) and old + L-arginine supplementation + exercise (Old Sup + Exe). LA CNPs were administered to the supplement groups through gavage at a dosage of 500 mg/kg/day for 6-weeks. Exercise groups were subjected to a swimming exercise program five days/week for the same duration. Upon the completion of their interventions, the animals underwent behavioral and open-field task tests and were subsequently sacrificed for hippocampus genetic and histopathological evaluation. For histopathological analysis of brain, Cresyl violet staining was used. Congo Red staining was employed to confirm amyloid plaques in the hippocampus. Expressions of Tau, App, Iba1, and ApoE genes were determined by real-time PCR. In contrast to the Old group, Old Exe and Old Sup + Exe groups spent more time in the central space in the open field task (p < 0.05) and have more live cells in the hippocampus. Old rats (Old, Old Sup and Old Exe groups) exhibited a significant Aß peptide accumulation and increases in APP, Tau, Iba1, APOE-4 mRNA and MDA, along with decreases in SOD compared to the young group (p < 0.05). However, LA CNPs supplementation, exercise, and their combination (Old Sup, Old Exe and Old Sup + Exe) significantly reduced MDA, Aß plaque as well as APP, Tau, Iba1, and APOE-4 mRNA compared to the Old group (p < 0.05). Consequently, the administration of LA CNPs supplements and exercise might regulate the risk factors of hippocampus cell and tissue.

Heart Rate and Acceleration Dynamics during Swim-Fitness and Stress Challenge Tests in Yellowtail Kingfish (Seriola lalandi).

The yellowtail kingfish is a highly active and fast-growing marine fish with promising potential for aquaculture. In this study, essential insights were gained into the energy economy of this species by heart rate and acceleration logging during a swim-fitness test and a subsequent stress challenge test. Oxygen consumption values of the 600-800 g fish, when swimming in the range of 0.2 up to 1 m·s-1, were high-between 550 and 800 mg·kg-1·h-1-and the heart rate values-up to 228 bpm-were even among the highest ever measured for fishes. When swimming at these increasing speeds, their heart rate increased from 126 up to 162 bpm, and acceleration increased from 11 up to 26 milli-g. When exposed to four sequential steps of increasing stress load, the decreasing peaks of acceleration (baseline values of 12 to peaks of 26, 19 and 15 milli-g) indicated anticipatory behavior, but the heart rate increases (110 up to 138-144 bpm) remained similar. During the fourth step, when fish were also chased, peaking values of 186 bpm and 44 milli-g were measured. Oxygen consumption and heart rate increased with swimming speed and was well reflected by increases in tail beat and head width frequencies. Only when swimming steadily near the optimal swimming speed were these parameters strongly correlated.

Swimming exercise ameliorates insulin resistance and nonalcoholic fatty liver by negatively regulating PPARγ transcriptional network in mice fed high fat diet.

BACKGROUND: Recent findings elucidated hepatic PPARγ functions as a steatogenic-inducer gene that activates de novo lipogenesis, and is involved in regulation of glucose homeostasis, lipid accumulation, and inflammation response. This study delved into a comprehensive analysis of how PPARγ signaling affects the exercise-induced improvement of insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD), along with its underlying mechanism. METHODS: Chronic and acute swimming exercise intervention were conducted in each group mice. IR status was assessed by GTT and ITT assays. Serum inflammatory cytokines were detected by Elisa assays. PPARγ and its target genes expression were detected by qPCR assay. Relative protein levels were quantified via Western blotting. ChIP-qPCR assays were used to detect the enrichment of PPARγ on its target genes promoter. RESULTS: Through an exploration of a high-fat diet (HFD)-induced IR and NAFLD model, both chronic and acute swimming exercise training led to significant reductions in body weight and visceral fat mass, as well as hepatic lipid accumulation. The exercise interventions also demonstrated a significant amelioration in IR and the inflammatory response. Meanwhile, swimming exercise significantly inhibited PPARγ and its target genes expression induced by HFD, containing CD36, SCD1 and PLIN2. Furthermore, swimming exercise presented significant modulation on regulatory factors of PPARγ expression and transcriptional activity. CONCLUSION: The findings suggest that swimming exercise can improve lipid metabolism in IR and NAFLD, possibly through PPARγ signaling in the liver of mice.

Effects of swimming exercise combined with silymarin and vitamin C supplementation on hepatic inflammation, oxidative stress, and histopathology in elderly rats with high-fat diet-induced liver damage.

OBJECTIVES: The aim of this study was to demonstrate that swimming exercise combined with silymarin and vitamin C supplementation improves hepatic inflammation, oxidative stress, and liver histopathology in elderly rats with high-fat diet-induced liver damage. METHODS: Forty elderly male Wistar rats were randomly assigned to five groups (n = 8 in each): a normal diet (control), a high-fat diet (HFD), HFD + silymarin and vitamin C supplementation (HFD+Sup), HFD + swimming exercise (HFD+Exe), and HFD+Sup+Exe group (HFD+Sup+Exe). The non-alcoholic fatty liver model was induced for 6 wk in the HFD groups. After 6 wk of consuming an HFD, a daily supplemental gavage was administered to rats as an intervention along with HFD in the supplement groups for 8 wk. Moreover, rats in the exercise groups were subjected to swimming exercise training 5 d/wk for the same period. RESULTS: The combination of swimming training and supplementation caused significant decreases in liver inflammatory biomarkers tumor necrosis factor-α and interleukin-1ß while increasing total antioxidant capacity and peroxisome proliferator-activated receptor α (P < 0.05). CONCLUSION: In elderly rats with liver injury caused by an HFD, the combination of exercise and silymarin with vitamin C supplementation effectively reduced oxidative stress, liver inflammation, fat accumulation, and regulated liver enzymes.

Pterostilbene Attenuates High-Intensity Swimming Exercise-Induced Glucose Absorption Dysfunction Associated with the Inhibition of NLRP3 Inflammasome-Induced IECs Pyroptosis.

The study investigated the effect of pterostilbene (PTE) on intestinal glucose absorption and its underlying mechanisms in high-intensity swimming exercise (HISE)-treated mice. Male C57BL/6 mice were treated with PTE for 4 weeks and performed high-intensity swimming training in the last week. Intestinal epithelial cells (IECs) were pretreated with 0.5 and 1.0 µM PTE for 24 h before being incubated in hypoxia/reoxygenation condition. Intestinal glucose absorption was detected by using an oral glucose tolerance test and d-xylose absorption assay, and the levels of factors related to mitochondrial function and pyroptosis were measured via western blot analyses, cell mito stress test, and quantitative real-time polymerase chain reaction. In vivo and in vitro, the results showed that PTE attenuated HISE-induced intestinal glucose absorption dysfunction and pyroptosis in mice intestine. Moreover, PTE inhibited NLRP3 inflammasome and the mitochondrial homeostasis as well as the ROS accumulation in IEC in vitro. Additionally, knockdown of SIRT3, a major regulator of mitochondria function, by siRNA or inhibiting its activity by 3-TYP abolished the effects of PTE on pyroptosis, mitochondrial homeostasis, and ROS generation of IEC in vitro. Our results revealed that PTE could alleviate HISE-induced intestinal glucose absorption dysfunction associated with the inhibition of NLRP3 inflammasome-induced IECs pyroptosis.

Swimming exercise reduces oxidative stress and liver damage indices of male rats exposed to electromagnetic radiation.

OBJECTIVES: Hepatic damage caused by oxidative stress is one of the problems associated with the emission of electromagnetic radiation (EMR). In this study, the effects of swimming exercise (SE) on oxidative stress and liver cell damage caused by EMR emission in rats were investigated. METHODS: Thirty-two rats (8 weeks old) were randomly divided into four groups, including control (C), EMR, SE, and EMR + SE. During four weeks, the animals engaged in SE (30 min/session, 5session/week) and were also exposed to EMR (4 h/day, seven days/week) emission from a Wi-Fi 2.45GHZ router. The liver and blood samples were collected at 48 h after completing four weeks of SE to assess histopathological damage, oxidative stress, and liver enzymes. KEY FINDINGS: Tissue sections showed severe liver damage in the EMR group compared to the C group, while the SE attenuated the liver damage. In the EMR group, compared to the C, SE and EMR + SE groups, the activity of superoxide dismutase (SOD) and catalase (CAT) decreased significantly, and the concentration of malondialdehyde (MDA) and liver enzymes (AST, ALT, and ALP) increased significantly (P < 0.05). Swimming exercise in the SE and EMR + SE groups compared to EMR led to a significant increase in the activity of SOD and CAT and a significant decrease in the concentration of MDA and liver enzymes (P < 0.05). CONCLUSION: The study findings showed that the SE is beneficial in attenuating the harmful effects of RF-EMR emitted from the Wi-Fi on the liver.

The Protective Effects of the Combination of Vitamin E and Swimming Exercise on Memory Impairment Induced by Exposure to Waterpipe Smoke.

BACKGROUND: Waterpipe smoking (WP) exposure involves a negative health impact, including memory deficit, which is attributed to the elevation of oxidative stress. Vitamin E (VitE) in combination with swimming exercise exerts protective effects that prevent memory impairment. In the current study, the modulation of WP-induced memory impairment by the combined effect of VitE and swimming exercise (SE) was investigated. METHODS: Animals were exposed to WP one hour/day, five days per week for four weeks. Simultaneously, VitE (100 mg/kg, six days/week for four weeks) was administered via oral gavage, and the rats were made to swim one hour/day, five days/week for four weeks. Changes in memory were evaluated using radial arm water maze (RAWM), and oxidative stress biomarkers were examined in the hippocampus. RESULTS: WP exposure induced short-term/long-term memory impairment (p<0.05). This impairment was prevented by a combination of VitE with SE (p<0.05). Additionally, this combination normalized the hippocampal catalase, GPx, and GSH/GSSG ratios that were modulated by WP (p<0.05). The combination further reduced TBARs levels below those of the control group (p<0.05). CONCLUSION: WP-induced memory impairments were prevented by the combination of VitE with SE. This could be attributed to preserving the hippocampal oxidative mechanism by combining VitE and SE during WP exposure.

Investigation of the effects of swimming exercises in rats given acrylamide.

BACKGROUND: Acrylamide is a toxic substance used in industrial and laboratory processes. Acrylamide exposure has a toxic effect on many systems. Protective mechanisms should be developed against the effects caused by acrylamide. OBJECTIVE: In our study, we investigated whether exercise has a protective effect against the changes that acrylamide will cause in pancreas. METHODS: 32 adult Sprague-Dawley male rats were used. Control group was given only saline. Exercise group was applied swimming exercise for 1hour daily for 4 weeks. Acrylamide group was given 50mg/kg acrylamide by gavage for 4 weeks. Acrylamide+exercise group was applied 50mg/kg acrylamide for 4 weeks and swimming exercise for 1hour daily. After the experiment, fasting blood glucose and oral glucose tolerance test measurements were performed. Then, blood and pancreas samples were taken. RESULTS: Acrylamide exposure caused an increase in fasting blood glucose and oral glucose tolerance, a decrease in insulin levels and oxidative stress in acrylamide group. In exercise group, these values were similar to control group and no significant change was observed in acrylamide+exercise group. While there was an increase in the number of alpha cells in acrylamide group compared to the other groups, here was a decrease in the number of beta cells compared to control group. CONCLUSION: We can say that acrylamide causes changes in the islets of Langerhans by affecting alpha and beta cell numbers. The protective effect of exercise on beta and alpha cell mass was not statistically significant in the acrylamide+exercise group. When the results were examined, the decrease in oxidative stress and the higher number of beta and alpha cells in the acrylamide+exercise group compared to the acrylamide group suggested that 4 weeks of swimming exercise may have an effect on acrylamide exposure.

Swimming exercise is a promising early intervention for autism-like behavior in Shank3 deletion rats.

INTRODUCTION: SHANK3 is an important excitatory postsynaptic scaffold protein, and its mutations lead to genetic cause of neurodevelopmental diseases including autism spectrum disorders (ASD), Philan McDermid syndrome (PMS), and intellectual disability (ID). Early prevention and treatment are important for Shank3 gene mutation disease. Swimming has been proven to have a positive effect on neurodegenerative diseases. METHODS: Shank3 gene exon 11-21 knockout rats were intervened by a 40 min/day, 5 day/week for 8-week protocol. After the intervention, the rats were tested to behavioral measures such as learning and memory, and the volume and H-spectrum of the brain were measured using MRI; hippocampal dendritic spines were measured using Golgi staining and laser confocal. RESULTS: The results showed that Shank3-deficient rats had significant deficits in social memory, object recognition, and water maze learning decreased hippocampal volume and number of neurons, and lower levels of related scaffold proteins and receptor proteins were found in Shank3-deficient rats. CONCLUSION: It is suggested that early swimming exercise has a positive effect on Shank3 gene-deficient rats, which provides a new therapeutic strategy for the prevention and recovery of neurodevelopmental disorders.

Protective effects of swimming exercises and metformin on cardiac and aortic damage caused by a high-fat diet in obese rats with type 2 diabetes, by regulating the Bcl2/Bax signaling pathway.

Background/aim: Due to the increasing mortality and morbidity rates in diabetes mellitus (DM), which is one of the biggest health problems of our age, many treatment modalities are still being tried. The positive effects of metformin (MET) and physical exercise (EXE) on the pathophysiology of diabetes are well known. In this study, it was aimed to detail these positive effects of MET and EXE in combination on the basis of inflammation, apoptosis mechanisms, and endogen nesfatin-1 (NES-1) synthesis. Materials and methods: Twenty-seven type 2 DM (DM-2) male Wistar Albino rats were divided into 4 groups, as the high-fat diet (HFD), MET, EXE, and MET+EXE groups. The total duration of the study was 3 months. At the end of the experiment, blood glucose and lipid profiles were measured. Histopathological evaluation was performed on the cardiac and aortic tissues and apoptotic markers were evaluated immunohistochemically. Inflammatory markers and NES-1 levels were analyzed by enzyme-linked immunosorbent assay. Results: The plasma glucose, homeostatic model evaluation-insulin resistance (HOMA-IR), low-density lipoprotein (LDL) levels increased, and high-density lipoprotein (HDL) levels decreased significantly in the HFD group. In the treatment groups, the glucose, HOMA-IR, LDL, NES-1 levels in the plasma, as well as tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), IL-6, caspase-3 (Cas-3), Bcl-2-associated X protein (Bax), and histopathological findings of inflammation in tissues were decreased. Additionally, there was an increase in plasma insulin, HDL, and tissue B-cell lymphoma-2 and levels. Conclusion: It was observed that the MET and EXE treatments in the DM-2 model reduced cellular damage mechanisms such as inflammation and apoptosis. The decrease in NES-1 levels was thought to be secondary to this antiinflammatory effect. In conclusion, the results demonstrated the effectiveness of EXE in reducing DM-2 and the NES-1 levels. Further studies are needed to evaluate the effect in different EXE models and treatment durations.

T 2-mapping and BOLD to evaluate the effect of swimming rehabilitation exercise on paraspinal muscles in rats model with discogenic low back pain / 中华放射学杂志

Objective:To explore MRI T 2-mapping and blood oxygenation level dependent (BOLD) to evaluate the functional changes of paraspinal muscle in rats with discogenic low back pain (DLBP) after swimming. Methods:Totally 54 female 1-month-old SD rats were selected, which were divided into 3 groups by random number table method, sham operation (Sham) group, DLBP non-swimming group and DLBP swimming group, with 18 rats in each group. Under the guidance of X-ray fluoroscopy, the L4/5 and L5/6 intervertebral discs of the rats in the DLBP non-swimming group and DLBP swimming group were punctured by the posterior approach, and establishment of DLBP rat model by destroying nucleus pulposus, and only paraspinal muscles at the same level were punctured in the Sham group. After modeling, the DLBP swimming group received swimming exercise intervention for 5 consecutive days (30 min/d), while the DLBP non-swimming group and Sham group did not receive any rehabilitation exercise intervention. Each group was divided into 3 time point subgroups on average, the T 2-mapping and BOLD sequences were scanned at 30, 90 and 180 days after modeling to obtain the T 2 value, R 2* value of the paraspinal muscles, and the paraspinal muscles at the modeling level were taken for immunofluorescence staining, and the fluorescence intensity of myosin heavy chain (MYH)1 (type Ⅱ muscle fiber) and MYH7 (type I muscle fiber) was analyzed. One-way analysis of variance was used for comparison among the 3 groups, and the Bonferroni method was used for multiple comparisons, and Pearson correlation coefficient was used to evaluate the correlation between quantitative MRI parameters T 2 value, R 2* value and MYH1, MYH7 immunofluorescence intensity of rat paraspinal muscles at 180 days after modeling. Results:At 30 days after modeling, there was no significant difference in T 2 value and R 2* value among the 3 groups (all P>0.05). At 90 days after modeling, the T 2 value of the DLBP swimming group was higher than that of the DLBP non-swimming group, and the T 2 value of the DLBP non-swimming group was lower than that of the Sham group (all P<0.05), and there was no significant difference in the R 2* value among the 3 groups ( P>0.05). At 180 days after modeling, the T 2 value of the DLBP swimming group was higher than that of the DLBP non-swimming group, and the R 2* value was lower than that of the DLBP non-swimming group; the T 2 value of the DLBP non-swimming group was lower than that of the Sham group, and the R 2* value was higher than that of the Sham group (all P<0.05). At 30 and 90 days after modeling, there was no significant difference in the expressions of MYH1 and MYH7 among the 3 groups (all P>0.05). At 180 days after modeling, the expression of MYH1 decreased and the expression of MYH7 increased in the DLBP swimming group compared with the DLBP non-swimming group; the expression of MYH1 increased and the expression of MYH7 decreased in the DLBP non-swimming group compared with the Sham group (all P<0.05). At 180 days after modeling, the T 2 value had a moderate negative correlation with the fluorescence intensity of MYH1 ( r=-0.511, P=0.043), and a moderate positive correlation with the fluorescence intensity of MYH7 ( r=0.564, P=0.023); R 2* value was moderate positive correlated with the fluorescence intensity of MYH1 ( r=0.625, P=0.010), and moderate negative correlated with the fluorescence intensity of MYH7 ( r=-0.653, P=0.006). Conclusions:Swimming exercise can improve the reduction of water content and perfusion in the paraspinal muscles of DLBP rats, and reduce the transformation of muscle fibers from type Ⅰ to type Ⅱ, the changes of T 2 and R 2* value can reflect the transformation of paraspinal muscle fiber types to a certain extent.

Recovering the angiogenic/angiostatic balance in NNK-induced lung carcinoma via 12 weeks of submaximal swimming and Nigella sativa nanocapsule.

Background: Carcinogen nitrosamine 4-(methyl-trosamino)-1-(3-pyridyl)-1-butanone (NNK) remarkably affects the actions of growth factors: EGFR, VEGFR-2, as well as the natural tumor suppressors: TGFß-1 and TIMP-1. We propose that utilizing non-chemical interventions such as swimming and Nigella sativa nanocapsule play role in controlling cancer progression through direct effects on tumor-inherent factors. Material and methods: Male rats were randomly placed into seven groups: Control (C), Solvent (S), (NNK), NNK+N.sativa (NNK+NS), NNK+Exercise (NNK+E), N.sativa+Exercise (NS+E), NNK+N.sativa+Exercise (NNK+NS+E). The exercise program consisted of 12 weeks of submaximal swimming. NNK and NS groups received weekly doses of 12/5 mg/kg and 125 µg/kg of NNK and N.sativa, respectively. By the end of the protocol, the levels of VEGFR-2, and TIMP-1 were determined using immunohistochemistry method and EGFR, and TGFß-1 levels were measured by RT-PCR assay. Results: In comparison with control group, there was a significant increase in the levels of VEGFR-2 in NNK, NNK+E, NNK+NS, NS+E, and NNK+NS+E groups (P ≤ 0.001), also TGFß-1 levels of NNK+E and NS+E groups significantly increased (P ≤ 0.001). While EGFR levels did not change remarkably (P˃0.05), except in NNK group (P ≤ 0.001), TIMP-1 in NNK, NNK+E, NS+E, NNK+NS+E groups significantly decreased (P ≤ 0.001). Conclusion: We recommend 12 weeks of submaximal swimming and 125 µg/kg N.sativa nanocapsule are safe interventions to recover the balance of selected angiogenic/ angiostatic markers and to control tumor initiation, growth, and metastasis in lung carcinoma induced by 12/5 mg/kg of NNK injection.

Managing MMP-2, MMP-9, VEGFR-2, TGFß-1, and TIMP-1 in NNK-induced lung carcinoma by nonchemical interventions in female rats.

Background: Smart and flexible methods are attracting remarkable interest in cancer-related biological and chemical therapies. To achieve a safer, affordable, and more effective cancer treatment, we evaluated the application of submaximal swimming and Nigella sativa (NS) nano-drug on lung tissues of female rats induced by NNK. Material and methods: A 12-weeks protocol of submaximal swimming was performed in pathologic and non-pathologic groups. NNK and NS groups, respectively received weekly doses of 12/5 mg/kg and 125 µg/kg of body weight. By the end of the protocol, the ratios of MMP-2, MMP-9, and TIMP-1 determined by using immunohistochemistry essay, and RT-PCR analysis for VEGFR-2 and TGFß-1. Results: As a result, treatment with exercise and NNK resulted in VEGFR-2 overexpression (P ≤ 0.001 and P ≤ 0.05, respectively). In NNK, NNK+E, NNK+NS, and NNK+NS+E groups, protein expression of MMP-2 and MMP-9 significantly increased, despite the reduction of TIMP-1 levels in the same groups compared to control (P ≤ 0.001). TGFß-1 ratio significantly increased following preformed interventions in non-pathologic groups: E (P ≤ 0.001) and NS+E (P ≤ 0.01). Conclusion: IHC and gene assays indicate a favorable and acceptable effect of the designed training protocol besides the treatment with N.sativa nano-drug, by which cancer development could be restricted through recovering the natural balance of angiogenic and angiostatic markers.

[Effects of different swimming exercises on alcoholic fatty liver formation in mice].

Objective: To investigate the effects of 7-week swimming exercise with different loads on the improvement of liver lipid metabolism in mice with alcoholic fatty liver disease (AFLD) and its relationship with the regulation of miR-34a/PPARα. Methods: Fifty male KM mice were randomly divided into control group (K, n=10) and alcoholic fatty liver group (AFLD, n=40). The AFLD model was constructed after feeding with 50% alcohol for 7 weeks with 1 d rest per week. After successful model construction, the mice were divided into a model group (M), a 30-min swimming exercise group (LE), a 60-min swimming exercise group (ME), and a 90-min loaded swimming exercise group (HE, 5% of body mass as tail lead load), with 10 mice in each group, for a total of 7 weeks of intervention. After completion, the serum and liver tissues were collected, the liver index, visceral fat ratio, hepatocyte injury indicators, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GT), total cholesterol (TC), triglyceride (TG), and high/low density lipoprotein cholesterol (H/LDL-C) content were measured; HE staining was used to observe the changes in liver structure, Western blot was used to detect the protein levels of PPARα, FAS and TNF-α in liver tissues, and mRNA expression profiles were analyzed by sequencing After RT-PCR, the mRNA expressions of miR-34a, PPARα, FAS, TNF-α and CPT-1 were verified. Results: Compared with K group, the hepatic cord disorder, focal lipid vacuum, obvious lipid droplet vacuolation, abnormal ectopic nucleus were observed in AFLD group ; liver function was decreased significantly. Compared with the M group, the liver functions of the ME and HE groups were improved significantly, the serum levels of TG, TC and LDL-C were decreased, while the HDL-C level was increased (P<0.01 or P<0.05), and the liver index and visceral fat ratio were decreased (P< 0.01 or P<0.05), the focal lipid droplet degeneration of hepatocytes was decreased, and the structure of the hepatic cord was clearer; and the ME group showed a more significant intervention effect. Compared with the M group, the expression levels of PPARα protein in the liver tissues of the LE, ME, and HE groups were increased, while the protein expression levels of FAS and TNF-α were decreased (P<0.01 or P<0.05). Based on Illumina high-throughput sequencing and mRNA differential expression analysis, there are 38 differentially expressed genes in the PPARα pathway, including 9 up-regulated genes and 29 down-regulated genes, which are involved in liver fatty acid oxidation, lipid metabolism, and apoptosis inhibition. Compared with group M, the gene levels of miR-34a, FAS, and TNF-α in LE, ME, and HE groups were decreased, and the gene levels of PPARα and CPT-1 were increased (P<0.01 or P<0.05). Conclusion: Swimming with different loads can improve liver functions in AFLD mice, promote lipid droplet degradation, and regulate liver lipid metabolism. The mechanism may be related to the activation of miR-34a/PPARα, and the intervention effect of moderate-load swimming is better.

VH-4-A Bioactive Peptide from Soybean and Exercise Training Constrict Hypertension in Rats through Activating Cell Survival and AMPKα1, Sirt1, PGC1α, and FoX3α.

Hypertension is a chronic disease related to age, which affects tens of millions of people around the world. It is an important risk factor that causes myocardial infarction, heart failure, stroke, and kidney damage. Bioactive peptide VHVV (VH-4) from soybean has shown several biological activities. Physical exercise is a cornerstone of non-pharmacologic treatment for hypertension and has established itself as an effective and complementary strategy for managing hypertension. The present study evaluates the efficacy of VH-4 supplement and swimming exercise training in preventing hypertension in spontaneously hypertensive rats (SHR). SHR animals were treated with VH-4 (25 mg/kg by intraperitoneal administration) and swimming exercise (1 h daily) for eight weeks, and the hemodynamic parameters, histology, and cell survival pathway protein expression were examined. In SHR rats, increased heart weight, blood pressure, and histological aberrations were observed. Cell survival protein p-PI3K and p-AKT and antiapoptosis proteins Bcl2 and Bcl-XL expression decreased in SHR animals. SIRT1 and FOXO3 were decreased in hypertensive rats. Both bioactive peptide VH-4 treatment and swimming exercise training in hypertensive rats increased the cell survival proteins p-PI3K and p-AKT and AMPKα1, Sirt1, PGC1α, and FoX3α proteins. Soy peptide VH-4, along with exercise, acts synergistically and prevents hypertension by activating cell survival and AMPKα1, Sirt1, PGC1α, and FoX3α proteins.