• Molecules and Cells
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• v.25 no.4
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• pp.531-537
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• 2008

Abnormal activation of nuclear factor kappa B ($NF-{\kappa}B$) probably plays an important role in the pathogenesis of Duchenne's muscular dystrophy (DMD). In this report, we evaluated the efficacy of curcumin, a potent $NF-{\kappa}B$ inhibitor, in mdx mice, a mouse model of DMD. We found that it improved sarcolemmic integrity and enhanced muscle strength after intraperitoneal (i.p.) injection. Histological analysis revealed that the structural defects of myofibrils were reduced, and biochemical analysis showed that creatine kinase (CK) activity was decreased. We also found that levels of tumor necrosis factor alpha ($TNF-\alpha$), interleukin-1 beta ($IL-1\beta$) and inducible nitric oxide synthase (iNOS) in the mdx mice were decreased by curcumin administration. EMSA analysis showed that $NF-{\kappa}B$ activity was also inhibited. We thus conclude that curcumin is effective in the therapy of muscular dystrophy in mdx mice, and that the mechanism may involve inhibition of $NF-{\kappa}B$ activity. Since curcumin is a non-toxic compound derived from plants, we propose that it may be useful for DMD therapy.

• Korean Journal of Applied Biomechanics
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• v.31 no.4
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• pp.308-313
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• 2021

Objective: The purpose of this study was to investigate the effect of different kettlebell mass (30%, 40%, and 50% of the body mass) on kinematics and kinetic variables of kettlebell swing. Method: Total of 16 healthy male who had at least 1 year of kettlebell training experience were participated in this study (age: 31.69 ± 3.46 yrd., height: 173.38 ± 4.84 cm, body mass: 74.53 ± 6.45 kg). In this study, a 13-segments whole-body model (upper trunk, lower trunk, pelvis, both side of forearm, upperarm, thigh, and shank) was used and 26 reflective markers were attached to the body to identify the segments during the movement. A 3-dimensional motion analysis with 8 infrared cameras and 4 channeled EMG was performed to find the effect of kettlebell mass on its swing. To verify the kettlebell mass effect, a one-way ANOVA with a repeated measure was used and the statistical significance level was set at 𝛼=.05. Results: Firstly, in all lower extremity joints and thoracic vertebrae, a statistically significant change in angle was shown according to an increase in kettlebell mass during kettlebell swing (p<.05). Secondly, in both the up-swing and down-swing phases, the knee joint and ankle joint ROM showed a statistically significant increase as the kettlebell mass increased (p<.05) but no statistically significant difference was found in the hip joint and thoracic spine (p>.05). Lastly, the hamstrings muscle activity was statistically significantly increased as the kettlebell mass increased during up-swing phases (p<.05). Also, as the kettlebell mass increased in P4 of the down swing phase, the gluteus maximus showed a statistically significantly increased muscle activation, whereas the rectus femoris showed a statistically significantly decreased muscle activation (p <.05). Conclusion: As a result of this study, hip extension decreased and knee extension increased at 40% and 50% of body mass, and the spine also failed to maintain neutrality and increased flexion. Also, when kettlebell swings are performed with 50% of body mass, synergistic muscle dominance appears over 30% and 40% of body mass, which is judged to have a risk of potential injury. Therefore, it is thought that for beginners who start kettlebell exercise, swing practice should be performed with 30% of body mass. In addition, even in the case of experienced seniors, as the weight increases, the potential injury risk may increase, so it is thought that caution should be exercised when performing swings with 40% and 50% of body mass. In conclusion, it is thought that increasing the weight after sufficiently training with 30% of the weight of all subjects performing kettlebell swing is a way to maximize the exercise effect as well as prevent injury.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.523-528
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• 2016

Urotensin II (UII) is a potent vasoactive peptide and mitogenic agent to induce proliferation of various cells including vascular smooth muscle cells (VSMCs). In this study, we examined the effects of a novel UII receptor (UT) antagonist, KR-36676, on vasoconstriction of aorta and proliferation of aortic SMCs. In rat aorta, UII-induced vasoconstriction was significantly inhibited by KR-36676 in a concentration-dependent manner. In primary human aortic SMCs (hAoSMCs), UII-induced cell proliferation was significantly inhibited by KR-36676 in a concentration-dependent manner. In addition, KR-36676 decreased UII-induced phosphorylation of ERK, and UII-induced cell proliferation was also significantly inhibited by a known ERK inhibitor U0126. In mouse carotid ligation model, intimal thickening of carotid artery was dramatically suppressed by oral treatment with KR-36676 (30 mg/kg/day) for 4 weeks compared to vehicle-treated group. From these results, it is indicated that KR-36676 suppress UII-induced proliferation of VSMCs at least partially through inhibition of ERK activation, and that it also attenuates UII-induced vasoconstriction and vascular neointima formation. Our study suggest that KR-36676 may be an attractive candidate for the pharmacological management of vascular dysfunction.

• BMB Reports
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• v.43 no.5
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• pp.337-343
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• 2010

Fenofibrate, an agonist of $PPAR{\alpha}$, plays an important role in activating many proteins catalyzing lipid metabolism, and it also has a considerable effect on improvement of insulin sensitivity in the diabetic condition. To investigate fenofibrate-dependent expression of peripheral tissue proteins in diabetes, we analyzed whole muscle or fat proteins of fenofibrate-fed OLETF rats, an animal model of type II diabetes, using 2-dimensional gel electrophoresis. We found that many proteins were specifically expressed in a fenofibrate-dependent manner in these diabetic rats. In particular, a functionally unknown C11orf59 protein was differentially expressed in the muscle tissues (about 5-fold increase) in fenofibrate-fed OLETF rats as compared to control rats. Additionally, the signal proteins phosphatidylethanolamine binding protein and IkB interacting protein were differentially regulated in the fenofibrate-treated adipose tissues. We suggest here that these proteins might be involved in controlling lipid or carbohydrate metabolism in diabetes via $PPAR{\alpha}$ activation.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.385-391
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• 2000

Using the patch-clamp technique, we investigated the alteration of 4-aminopyridine(4-AP)-sensitive, voltage-dependent $K^+$ channel (Kv) in the mesenteric arterial smooth muscle cell (MASMC) of renovascular hypertensive model, one-kidney one-clip Goldblatt hypertensive rat (GBH). To isolate $K_V$ current, internal pipette solution contained 5 mM ATP and 10 mM EGTA. Under these condition, MASMC was depolarized by 4-AP, but charybdotoxin did not affect membrane potential. Membrane potential of hypertensive cell $(-40.3{\pm}3.2\;mV)$ was reduced when compared to that of normotensive cell $(-59.5{\pm}2.8\;mV).$ Outward $K^+$ current of hypertensive cell was significantly reduced when compared to normotensive cell. At 60 mV, the outward currents were $19.10{\pm}1.91$ and $14.06{\pm}1.05$ pA/pF in normotensive cell and hypertensive cell respectively. 4-AP-sensitive $K^+$ current was also smaller in hypertensive cell $(4.28{\pm}0.38\;pA/pF)$ than in normotensive cell $(7.65{\pm}0.52\;pA/pF).$ The values of half activation voltage $(V_{1/2})$ and slope factor (k1) as well as the values of half inactivation voltage $(V_{1/2})$ and slope factor (k1) were virtually similar between GBH and NTR. These results suggest that the decrease of 4-AP-sensitive $K^+$ current contributes to a depolarization of membrane potential, which leads to development of vascular tone in GBH.

• Molecules and Cells
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• v.43 no.8
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• pp.749-762
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• 2020

The migration, dedifferentiation, and proliferation of vascular smooth muscle cells (VSMCs) are responsible for intimal hyperplasia, but the mechanism of this process has not been elucidated. WD repeat domain 1 (WDR1) promotes actin-depolymerizing factor (ADF)/cofilin-mediated depolymerization of actin filaments (F-actin). The role of WDR1 in neointima formation and progression is still unknown. A model of intimal thickening was constructed by ligating the left common carotid artery in Wdr1 deletion mice, and H&E staining showed that Wdr1 deficiency significantly inhibits neointima formation. We also report that STAT3 promotes the proliferation and migration of VSMCs by directly promoting WDR1 transcription. Mechanistically, we clarified that WDR1 promotes the proliferation and migration of VSMCs and neointima formation is regulated by the activation of the JAK2/STAT3/WDR1 axis.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.127-134
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• 2018

Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB ($NF-{\kappa}B$) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.

• Physical Therapy Korea
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• v.28 no.2
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• pp.123-131
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• 2021

Background: Only 2% of falls in older adults result in serious injuries (i.e., hip fracture). Therefore, it is important to differentiate injurious versus non-injurious falls, which is critical to develop effective interventions for injury prevention. Objects: The purpose of this study was to a. extract the best features of surface electromyography (sEMG) for classification of injurious falls, and b. find a best model provided by data mining techniques using the extracted features. Methods: Twenty young adults self-initiated falls and landed sideways. Falling trials were consisted of three initial fall directions (forward, sideways, or backward) and three knee positions at the time of hip impact (the impacting-side knee contacted the other knee ("knee together") or the mat ("knee on mat"), or neither the other knee nor the mat was contacted by the impacting-side knee ("free knee"). Falls involved "backward initial fall direction" or "free knee" were defined as "injurious falls" as suggested from previous studies. Nine features were extracted from sEMG signals of four hip muscles during a fall, including integral of absolute value (IAV), Wilson amplitude (WAMP), zero crossing (ZC), number of turns (NT), mean of amplitude (MA), root mean square (RMS), average amplitude change (AAC), difference absolute standard deviation value (DASDV). The decision tree and support vector machine (SVM) were used to classify the injurious falls. Results: For the initial fall direction, accuracy of the best model (SVM with a DASDV) was 48%. For the knee position, accuracy of the best model (SVM with an AAC) was 49%. Furthermore, there was no model that has sensitivity and specificity of 80% or greater. Conclusion: Our results suggest that the classification model built upon the sEMG features of the four hip muscles are not effective to classify injurious falls. Future studies should consider other data mining techniques with different muscles.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.252-260
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• 2019

Background: Increases in the average global temperature cause heat stress-induced disorders by disrupting homeostasis. Excessive heat stress triggers an imbalance in the immune system; thus protection against heat stress is important to maintain immune homeostasis. Korean ginseng (Panax ginseng Meyer) has been used as a herbal medicine and displays beneficial biological properties. Methods: We investigated the protective effects of Korean ginseng extracts (KGEs) against heat stress in a rat model. Following acclimatization for 1 week, rats were housed at room temperature for 2 weeks and then exposed to heat stress ($40^{\circ}C$/2 h/day) for 4 weeks. Rats were treated with three KGEs from the beginning of the second week to the end of the experiment. Results: Heat stress dramatically increased secretion of inflammatory factors, and this was significantly reduced in the KGE-treated groups. Levels of inflammatory factors such as heat shock protein 70, interleukin 6, inducible nitric oxide synthase, and tumor necrosis factor-alpha were increased in the spleen and muscle upon heat stress. KGEs inhibited these increases by down-regulating heat shock protein 70 and the associated nuclear $factor-{\kappa}B$ and mitogen-activated protein kinase signaling pathways. Consequently, KGEs suppressed activation of T-cells and B-cells. Conclusion: KGEs suppress the immune response upon heat stress and decrease the production of inflammatory cytokines in muscle and spleen. We suggest that KGEs protect against heat stress by inhibiting inflammation and maintaining immune homeostasis.

• The Journal of Korean Medicine
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• v.20 no.2
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• pp.108-120
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• 1999

In this study, body weight levels of glucose, insulin and triglyceride in blood and glucosidase activity of the small intestine were investigated to determine the effect of Sangbaegpitang and Supungsungiwhan on the glucose metabolism of db/db mice. The GLUT4 mRNA of muscle tissue and the Acetyl CoA Carboxylase and the activation rate of GLUT2 mRNA of liver tissue were measured by the reverse transcription-polymerase chain reaction method and by the vitro transcription. The results were obtained as follows: 1. In the Sangbaegpitang administration group, (1) The level of triglyceride was decreased significantly and the glucosidase activity of the small intestine was inhibited remarkably, (2) The amounts of the GLUT4 mRNA in muscle tissue and Acetyl CoA Carboxylase mRNA in liver tissue were increased significantly. (3) Though glucose level in both fasting and non-fasting, were decreased and the insulin level in blood was increased, the results showed no statistical significance. 2. In the Supungsungiwhan administration group, (1) The levels of glucose and triglyceride were decreased significantly in the blood of non-fasting animals. (2) The glucosidase activity of small intestine was inhibited markedly and the amounts of GLUT4 mRNA of muscle tissue and GLUT2 mRNA of liver tissue were increased significantly. (3) The glucose levels in the fasting group were reduced, while insulin level was increased but showed no statistical significance, Based on the above results, our conclusions are as follows: Sangbaegpitang & Supungsungiwhan are thought to be capable of inhibiting the activity glucosidase, the enzyme which influences carbohydrate metabolism in the small intestine of db/db mice(the experimental diabetic model) and delaying the absorption of carbohydrate, thus proving effective on inhibiting the increase of non-fasting glucose level effectively. Futhermore Sangbaegpitang and Supungsungiwhan are though: to be capable of preventing the composition of free fatty acids by restoring the production of GLUT4 mRNA of muscle tissues and GLUT2 mRNA of liver tissues. Those results suggests that above prescriptions can be applied to non-insulin dependent diabetes mellitus in order to improve insulin resistance.