Effect of Core Balance Training on Muscle Tone and Balance Ability in Adult Men and Women.

(1) Background: The amount of physical activity most adults perform is less than the recommended amount, and the resulting decrease in physical strength makes them vulnerable to various diseases. A decrease in muscle size and strength due to damage caused by disease or aging negatively affects functional strength. Muscle evaluation in adults can yield results that are predictive indicators of aging and unexpected disability. In addition, balance ability is essential to prevent falls and injuries in daily life and maintain functional activities. It is important to develop and strengthen balance in the lower extremities and core muscles to maintain and enhance overall body balance. This study aimed to analyze the effects of core balance training on muscle tone and balance ability in adults. (2) Methods: The participants of this study were 32 adult male and female university students (male: mean age = 21.3 ± 1.9 years, weight = 74.2 ± 12.6 kg, BMI = 23.4 + 2.5, n = 14; female: mean age = 21.0 ± 1.4 years, weight = 64.6 + 1.2 kg, BMI = 22.4 ± 2.4, n =18). Thirty-two adults (training group: 16, control group: 16; male: 16, female: 16) participated in the Myoton PRO (gastrocnemius lateral/medial, tibialis anterior), Pedalo balance system, and Y-balance test. (3) Results: The following results were obtained for muscle elasticity, stiffness, and dynamic/static balance ability after 10 weeks of core balance training. 1. There was no significant difference in muscle elasticity (gastrocnemius lateral/medial, tibialis anterior) (p < 0.05). 2. Muscle stiffness (gastrocnemius lateral/medial, tibialis anterior) significantly increased (p < 0.05). 3. Dynamic/static balance ability significantly increased (p < 0.05). (4) Conclusions: In future, data for the age and sex of various participants, should be accumulated by recruiting participants to study muscle characteristics, such as muscle elasticity and stiffness. Estimating the appropriate injury range and optimal exercise capacity is possible through follow-up studies. The findings can then be used as a basis for predicting injuries or determining and confirming the best time to resume exercise.

A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells.

Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer and the leading cause of global cancer-related mortality. Despite the earlier identification of membrane-proximal cleavage of cell adhesion molecule 1 (CADM1) in cancers, the role of the membrane-bound fragment of CAMD1 (MF-CADM1) is yet to be clearly identified. In this study, we first isolated MF-CADM1-specific fully human single-chain variable fragments (scFvs) from the human synthetic scFv antibody library using the phage display technology. Following the selected scFv conversion to human immunoglobulin G1 (IgG1) scFv-Fc antibodies (K103.1-4), multiple characterization studies, including antibody cross-species reactivity, purity, production yield, and binding affinity, were verified. Finally, via intensive in vitro efficacy and toxicity evaluation studies, we identified K103.3 as a lead antibody that potently promotes the death of human SCLC cell lines, including NCI-H69, NCI-H146, and NCI-H187, by activated Jurkat T cells without severe endothelial toxicity. Taken together, these findings suggest that antibody-based targeting of MF-CADM1 may be an effective strategy to potentiate T cell-mediated SCLC death, and MF-CADM1 may be a novel potential therapeutic target in SCLC for antibody therapy.

Exercise Training Attenuates Ovariectomy-Induced Alterations in Skeletal Muscle Remodeling, Apoptotic Signaling, and Atrophy Signaling in Rat Skeletal Muscle.

PURPOSE: The effects of aerobic exercise training on soleus muscle morphology, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in ovariectomized rat skeletal muscle were investigated. METHODS: Female Sprague-Dawley rats were divided into control (CON), ovariectomy (OVX), and ovariectomy plus exercise (OVX+EX) groups. After ovarian excision, exercise training was performed using a rat treadmill at 20 m/min, 50 min/day, 5 days/week for 12 weeks. Protein levels of mitochondria-mediated apoptotic signaling and atrophy/hypertrophy signaling in the skeletal muscle (soleus) were examined through western immunoblot analysis. RESULTS: The number of myocytes and myocyte cross-sectional area (CSA) were increased and the extramyocyte space was decreased in the OVX group compared to those in the CON group. However, aerobic exercise training significantly increased myocyte CSA and decreased extramyocyte space in the OVX+EX group compared to those in the OVX group. The protein levels of proapoptotic signaling and muscle atrophy signaling were significantly increased, whereas the protein levels of muscle hypertrophy signaling were significantly decreased in the OVX group compared to that in the CON group. Aerobic exercise training significantly decreased the protein levels of proapoptotic signaling and increased the protein level of antiapoptotic protein in the OVX+EX group compared to that in the OVX group. Aerobic exercise training significantly increased the protein levels of hypertrophy signaling and decreased protein levels of atrophy signaling in the OVX+EX group compared to those in the OVX group. CONCLUSION: Treadmill exercise improved estrogen deficiency-induced impairment in skeletal muscle remodeling, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in skeletal muscle.

Does Obesity Affect the Severity of Exercise-Induced Muscle Injury?

This literature review investigates the effects of obesity on exercise-induced muscle injury and reexamines the potential mechanisms of exercise-induced muscle injury related to obesity. Several studies reported that high body mass index and percent body fat can significantly affect the markers of muscle injury after exercise, including maximal strength, delayed onset muscle soreness, creatinine kinase level, and myoglobin level. The potential mechanisms resulting in these outcomes include structural changes in the cell membrane induced by high fat levels, increased inflammatory responses due to adipose tissues, reduced muscle satellite cell activation and myogenesis due to lipid overload, differences in muscle fiber distributions, and sedentary behaviors. These mechanisms, however, must be verified through more research. As obesity is a potential risk factor increasing the severity of exercise-induced muscle injuries, the exercise intensity and duration for obese patients must be carefully selected, and a preconditioning intervention (e.g., low-intensity eccentric training) may be considered before or during the early stages of the exercise program.

Recent Advances in Monoclonal Antibody Therapy for Colorectal Cancers.

Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. Recent advances in recombinant DNA technology have led to the development of numerous therapeutic antibodies as major sources of blockbuster drugs for CRC therapy. Simultaneously, increasing numbers of therapeutic targets in CRC have been identified. In this review, we first highlight the physiological and pathophysiological roles and signaling mechanisms of currently known and emerging therapeutic targets, including growth factors and their receptors as well as immune checkpoint proteins, in CRC. Additionally, we discuss the current status of monoclonal antibodies in clinical development and approved by US Food and Drug Administration for CRC therapy.

Exercise and Curcumin in Combination Improves Cognitive Function and Attenuates ER Stress in Diabetic Rats.

Type 2 diabetes mellitus (T2DM) is a metabolic disease associated with chronic low-grade inflammation that is mainly associated with lifestyles. Exercise and healthy diet are known to be beneficial for adults with T2DM in terms of maintaining blood glucose control and overall health. We investigated whether a combination of exercise and curcumin supplementation ameliorates diabetes-related cognitive distress by regulating inflammatory response and endoplasmic reticulum (ER) stress. This study was performed using male Otsuka Long-Evans Tokushima Fatty (OLETF) rats (a spontaneous diabetes Type 2 model) and Long-Evans Tokushima Otsuka (LETO) rats (LETO controls) by providing them with exercise alone or exercise and curcumin in combination. OLETF rats were fed either a diet of chow (as OLETF controls) or a diet of chow containing curcumin (5 g/kg diet) for five weeks. OLETF rats exercised with curcumin supplementation exhibited weight loss and improved glucose homeostasis and lipid profiles as compared with OLETF controls or exercised OLETF rats. Next, we examined cognitive functions using a Morris water maze test. Exercise plus curcumin improved escape latency and memory retention compared to OLETF controls. Furthermore, OLETF rats exercised and fed curcumin had lower IL6, TNFα, and IL10 levels (indicators of inflammatory response) and lower levels of ER stress markers (BiP and CHOP) in the intestine than OLETF controls. These observations suggest exercise plus curcumin may offer a means of treating diabetes-related cognitive dysfunction.

Enterococcus faecalis EF-2001 protects DNBS-induced inflammatory bowel disease in mice model.

Recent studies have demonstrated the immunomodulatory effects of heat-killed lactic acid bacteria. The aim of this study was to evaluate the protective effect of heat-killed Enterococcus faecalis EF-2001 (EF-2001) on a model of inflammatory bowel disease (IBD). A total of 28 female NC/Nga mice were divided into 4 treatment groups. Controls were fed a normal commercial diet. In the experimental groups, colitis was induced by rectal administration of dinitrobenzene sulfonic acid. Two groups were orally administered 2 and 17 mg/kg EF-2001, respectively. EF-2001 treatment decreased the expression of several cytokines, including cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), interferon (IFN)-γ, interleukin (IL)-1ß, and IL-6 in inflamed colon compared to the DNBS alone group. In addition, EF-2001 suppressed DNBS-induced colonic tissue destruction. Therefore, this study strongly suggests that EF-2001 could alleviate the inflammation associated with mouse IBD.

Resistance Exercise Training Attenuates the Loss of Endogenous GLP-1 Receptor in the Hypothalamus of Type 2 Diabetic Rats.

The aim of this study was to investigate the effects of resistance exercise training on hypothalamic GLP-1R levels and its related signaling mechanisms in T2DM. The animals were separated into three groups: a non-diabetic control (CON), diabetic control (DM), and diabetic with resistance exercise (DM + EXE) group. The resistance exercise training group performed ladder climbing (eight repetitions, three days per week for 12 weeks). Body weight was slightly lower in the DM + EXE group than the DM group, but difference between the groups was not significant. Food intake and glucose were significantly lower in the DM + EXE group than in the DM group. The blood insulin concentration was significantly higher and glucagon was significantly lower in the DM + EXE group. The DM + EXE group in the hypothalamus showed significant increases in GLP-1R mRNA, protein kinase A (PKA), glucose transporter 2 (GLUT2), and protein kinase B (AKT) and significant decrease in protein kinase C-iota (PKC-iota). Antioxidant enzymes and apoptosis factors were significantly improved in the DM + EXE group compared with the DM group in the hypothalamus. The results suggest that resistance exercise contributes to improvements the overall health of the brain in diabetic conditions.

Exercise Training Attenuates Obesity-Induced Skeletal Muscle Remodeling and Mitochondria-Mediated Apoptosis in the Skeletal Muscle.

Obesity is characterized by the induction of skeletal muscle remodeling and mitochondria-mediated apoptosis. Exercise has been reported as a positive regulator of skeletal muscle remodeling and apoptosis. However, the effects of exercise on skeletal muscle remodeling and mitochondria-mediated apoptosis in obese skeletal muscles have not been clearly elucidated. Four-week-old C57BL/6 mice were randomly assigned into four groups: control (CON), control plus exercise (CON + EX), high-fat diet (HFD), and HFD plus exercise groups (HFD + EX). After obesity was induced by 20 weeks of 60% HFD feeding, treadmill exercise was performed for 12 weeks. Exercise ameliorated the obesity-induced increase in extramyocyte space and a decrease in the cross-sectional area of the skeletal muscle. In addition, it protected against increases in mitochondria-mediated apoptosis in obese skeletal muscles. These results suggest that exercise as a protective intervention plays an important role in regulating skeletal muscle structure and apoptosis in obese skeletal muscles.

Effects of resistance exercise on antioxidant enzyme activities and apoptosis-related protein expression of hippocampus in OLETF rats.

BACKGROUND: Studies on antioxidant enzyme activity and apoptosis related protein expression associated with diabetes are mainly limited to aerobic exercise. Since the effectiveness and efficiency of the resistance to diabetes has recently emerged, it is necessary to investigate the effects of regular resistance exercise on these factors. OBJECTIVE: The purpose of this study was to investigate the effects of resistance exercise on antioxidant enzymes activities and apoptosis related protein expression in hippocampus of diabetic rats. METHODS: Twenty-one male rats were divided into 3 groups: LETO (control group), OLETF (diabetes group) and OLETF + EX (OLETF with resistance exercise group). Resistance exercise consisted of ladder climbing every 5 days for 30 minutes for 8 weeks. The exercise group was trained to climb a 180-cm vertical ladder with weights secured to their tails. Antioxidant enzyme activities, apoptosis related protein expression, and HOMA-IR level were measured. RESULTS: The lipid peroxide and superoxide dismutase (SOD) activity were significantly increased in OLETF + EX compared to OLETF (p< 0.001). Glutathione peroxidase (GPx) activity was significantly lower in OLETF + EX than OLETF (p< 0.001). Caspase-3 expression of hippocampus was significantly decreased in OLETF + EX compared to OLETF (p< 0.05). Bax protein expression was significantly lower in OLETF + EX than OLETF (p< 0.05) whereas Bcl-2 expression was significantly higher in OLETF + EX than OLETF (p< 0.05). HOMA-IR level was significantly decreased in OLETF + EX compared to OLETF (p< 0.05). CONCLUSIONS: Regular resistance exercise intervention can decrease oxidative stress by enhancing antioxidant enzyme activity and this may lead to attenuate apoptosis related protein such as caspase-3, bax and bcl-2 expression in hippocampus of diabetic population.

Up-regulation of lipolysis genes and increased production of AMP-activated protein kinase protein in the skeletal muscle of rats after resistance training.

The purpose of this study was to investigate the expression of lipogenesis- and lipolysis-related genes and proteins in skeletal muscles after 12 weeks of resistance training. Sprague-Dawley rats (n=12) were randomly divided into control (resting) and resistance training groups. A tower-climbing exercise, in which rats climbed to the top of their cage with a weight applied to their tails, used for resistance training. After 12 weeks, rats from the resistance training group had lower body weights (411.66±14.71 g vs. 478.33±24.63 g in the control), there was no significant difference between the two groups in the concentrations of total cholesterol, and high or low density lipoprotein cholesterol. However, the concentration of triglyceride was lower in resistance-trained rats (59.83±14.05 µg/mL vs 93.33±33.89 µg/mL in the control). The mRNA expression levels of the lipogenesis-related genes sterol regulatory element binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase were not significantly different between the resistance-trained and control rats; however, mRNA expression of the lipolysis-related carnitine palmitoyl transferase 1 and malonyl-CoA decarboxylase increased significantly with resistance training. AMP-activated protein kinase protein levels also significantly increased in resistance training group compared with in the control group. These results suggested that resistance exercise training contributing to reduced weight gain may be in part be due to increase the lipolysis metabolism and energy expenditure in response to resistance training.

Resistance exercise training increase activation of AKT-eNOS and Ref-1 expression by FOXO-1 activation in aorta of F344 rats.

PURPOSE: This study investigated the effects of resistance exercise on the Akt-eNOS, the activation of antioxidant protein and FOXO1 in the aorta of F344 rats. METHODS: Male 7 week-old F344 rats were randomly divided into 2 groups: a climbing group (n = 6) and a sedentary group (n = 6). H&E staining and western blotting were used to analyze the rat aortas and target proteins. RESULTS: Resistance exercise training did not significantly affect aortic structure. Phosphorylation of AKT and eNOS and expression of MnSOD and Ref-1 were significantly increased while FOXO1 phosphorylation was significantly decreased in the resistance exercise group compared with the sedentary group. CONCLUSION: We demonstrate that resistance exercise activates the Akt-eNOS and Ref-1 protein without changes to aortic thickness via FOXO-1 activation in the aorta of F344 rats.

Artemisia asiatica Nakai Attenuates the Expression of Proinflammatory Mediators in Stimulated Macrophages Through Modulation of Nuclear Factor-κB and Mitogen-Activated Protein Kinase Pathways.

The present study aimed to examine the anti-inflammatory effects and potential mechanism of action of Artemisia asiatica Nakai (A. asiatica Nakai) extract in activated murine macrophages. A. asiatica Nakai extract showed dose-dependent suppression of lipopolysaccharide (LPS)-induced nitric oxide, inducible nitric oxide synthase, and cyclooxygenase-2 activity. It also showed dose-dependent inhibition of nuclear factor-κB (NF-κB) translocation from the cytosol to the nucleus and as an inhibitor of NF-κB-alpha phosphorylation. The extract's inhibitory effects were found to be mediated through NF-κB inhibition and phosphorylation of extracellular signal-regulated kinase 1/2 and p38 in LPS-stimulated J774A.1 murine macrophages, suggesting a potential mechanism for the anti-inflammatory activity of A. asiatica Nakai. To our knowledge, this is the first report of the anti-inflammatory effects of A. asiatica Nakai on J774A.1 murine macrophages; these results may help develop functional foods possessing an anti-inflammatory activity.

Sudden detraining deteriorates swimming training-induced enhancement of short-term and spatial learning memories in mice.

In the present study, we investigated the effect of swimming training and sudden detraining on learning ability and spatial memory capability and on neurogenesis and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of mice. Male ICR mice were randomly assigned into three groups (n= 15 in each group): the control group, the swimming training group, and the detraining group. The mice in the swimming training group were made to swim (6 days/week, 60 min/day) for 8 weeks. The mice in the detraining group were accomplished the same swimming program for 4 weeks and then discontinued exercise for 4 weeks. In the present results, enhanced short-term and spatial learning memories and increased hippocampal neurogenesis and BDNF expression were observed in the mice of the swimming training group. In contrast, decreased short-term and spatial learning memories were observed in the mice of the swimming detraining group compared to the control level. Hippocampal neurogenesis and BDNF expression were also decreased in the mice of the detraining group near to the control level. Here in this study, we suggest that sudden cessation of exercise training might bring decline of the brain functions.

Age-dependent effect of treadmill exercise on hemorrhage-induced neuronal cell death in rats.

Intracerebral hemorrhage (ICH) is a major cause of death and disability in the elderly. In the present study, we examined the age-dependence of the effect of treadmill exercise on the intrastriatal hemorrhage-induced neuronal cell death in rats. Young (8 weeks old) and old (64 weeks old) Sprague-Dawley male rats were used in the present study. Intrastriatal hemorrhage was induced by injection of 0.2 U collagenase (1 µL volume) into the striatum using a stereotaxic instrument. The rats in the exercise groups were forced to run on a treadmill for 30 min daily for 7 days. Lesion size was determined by Nissl staining. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. In the present results, induction of hemorrhage increased lesion size and enhanced apoptosis. Treadmill exercise decreased the lesion size with suppressing apoptosis. However, the size of lesion induced by hemorrhage and the number of apoptotic cells were not different between young and old rats. Treadmill exercise significantly reduced the ICH-induced lesion size and the number of apoptotic cells irrespective of age. The data suggest that treadmill exercise may provide therapeutic value against ICH by suppressing neuronal apoptosis regardless of age.

Volumetric analysis of cerebellum in short-track speed skating players.

The cerebellum is associated with balance control and coordination, which might be important for gliding on smooth ice at high speeds. A number of case studies have shown that cerebellar damage induces impaired balance and coordination. As a positive model, therefore, we investigated whether plastic changes in the volumes of cerebellar subregions occur in short-track speed skating players who must have extraordinary abilities of balance and coordination, using three-dimensional magnetic resonance imaging volumetry. The manual tracing was performed and the volumes of cerebellar hemisphere and vermian lobules were compared between short-track speed skating players (n=16) and matched healthy controls (n=18). We found larger right cerebellar hemisphere volume and vermian lobules VI-VII (declive, folium, and tuber) in short-track speed skating players in comparison with the matched controls. The finding suggests that the specialized abilities of balance and coordination are associated with structural plasticity of the right hemisphere of cerebellum and vermian VI-VII and these regions play an essential role in balance and coordination.

Effect of treadmill exercise on Purkinje cell loss and astrocytic reaction in the cerebellum after traumatic brain injury.

The cerebellum is one of the brain areas, which is selectively vulnerable to forebrain traumatic brain injuries (TBI). Physical exercise in animals is known to promote cell survival and functional recovery after brain injuries. However, the detailed pathologic and functional alterations by exercise following an indirect cerebellar injury induced by a TBI are largely unknown. We determined the effects of treadmill exercise on survival of Purkinje neurons and on a population of reactive astrocytes in the gyrus of lobules VIII and IX of the cerebellum after TBI. The rats were divided into four groups: the sham-operation group, the sham-operation with exercise group, the TBI-induction group, and the TBI-induction with exercise group. Cell biological changes of Purkinje neurons following indirect cerebellar injury were analyzed by immunohistochemistry. TBI-induced loss of calbindin-stained Purkinje neurons in the posterior region of the cerebellum and TBI also increased formation of reactive astroyctes in both the granular and molecular layers of the cerebellar posterior region. Treadmill exercise for 10 days after TBI increased the number of calbindin-stained Purkinje neurons and suppressed formation of reactive astroyctes. The present study provides the possibility that treadmill exercise may be an important mediator to enhance survival of Purkinje neurons in TBI-induced indirect cerebellar injury.