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Anti-fatigue effect of tormentic acid through alleviating oxidative stress and energy metabolism-modulating property in C2C12 cells and animal models

  • Ho-Geun Kang;Jin-Ho Lim;Hee-Yun Kim;Hyunyong Kim;Hyung-Min Kim;Hyun-Ja Jeong
    • Nutrition Research and Practice
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    • v.17 no.4
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    • pp.670-681
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    • 2023
  • BACKGROUND/OBJECTIVES: Oxidative stress is caused by reactive oxygen species and free radicals that accelerate inflammatory responses and exacerbate fatigue. Tormentic acid (TA) has antioxidant and anti-inflammatory properties. Thus, the aim of present study is to determine the fatigue-regulatory effects of TA in H2O2-stimulated myoblast cell line, C2C12 cells and treadmill stress test (TST) and forced swimming test (FST) animal models. MATERIALS/METHODS: In the in vitro study, C2C12 cells were pretreated with TA before stimulation with H2O2. Then, malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase (CK) activity, tumor necrosis factor (TNF)-α, interleukin (IL)-6, superoxide dismutase (SOD), catalase (CAT), glycogen, and cell viability were analyzed. In the in vivo study, the ICR male mice were administered TA or distilled water orally daily for 28 days. FST and TST were then performed on the last day. In addition, biochemical analysis of the serum, muscle, and liver was performed. RESULTS: TA dose-dependently alleviated the levels of MDA, LDH, CK activity, TNF-α, and IL-6 in H2O2-stimulated C2C12 cells without affecting the cytotoxicity. TA increased the SOD and CAT activities and the glycogen levels in H2O2-stimulated C2C12 cells. In TST and FST animal models, TA decreased the FST immobility time significantly while increasing the TST exhaustion time without weight fluctuations. The in vivo studies showed that the levels of SOD, CAT, citrate synthase, glycogen, and free fatty acid were increased by TA administration, whereas TA significantly reduced the levels of glucose, MDA, LDH, lactate, CK, inflammatory cytokines, alanine transaminase, aspartate transaminase, blood urea nitrogen, and cortisol compared to the control group. CONCLUSIONS: TA improves fatigue by modulating oxidative stress and energy metabolism in C2C12 cells and animal models. Therefore, we suggest that TA can be a powerful substance in healthy functional foods and therapeutics to improve fatigue.

Impact of concurrent inspiratory muscle and aerobic exercise training on pulmonary function and cardiopulmonary responses (흡기근육 훈련과 유산소운동의 동시적용이 심폐반응과 폐기능에 미치는 영향)

  • Jung, H.J.;Lee, D.T.
    • Exercise Science
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    • v.21 no.3
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    • pp.373-384
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    • 2012
  • The effects of inspiratory muscle training in conjunction with aerobic exercise on inspiratory muscle strength, pulmonary function, and maximal oxygen uptake(VO2max) were examined. Twenty four healthy collegiate men were divided into three groups; respiratory muscle training group(RTG; n=8), running exercise group(REG; n=8), and both respiratory muscle training and running group(BTG; n=8). Their pulmonary function, maximal inspiratory pressures(PImax), and VO2max were assessed before and after intervention. RTG underwent inspiratory muscle training(IMT) with load set to 50 % of PImax, 30 times per session, twice a day, 4 days a week REG ran on a treadmill at 70-75 % of VO2max for 30 min a day, 4 days a week. BTG participated both IMT and the running exercise. Participant's anthropometric parameters and pulmonary function were not changed. VO2max increased by 6.1±3.3 %, 5.9±6.6 %, and 10.0±8.3 % in RTG, REG, and BTG, respectively(p< .05), and PImax also increased by 21.7±14.3 %, 19.7±12.0 %, and 27.0±12.1 % in RTG, REG, and BTG, respectively, but no group differences were found. Based on the study, although statistically insignificant, BTG showed the biggest increase of VO2max and PImax indicating a possible synergic effect of inspiratory muscle training and aerobic exercise on respiratory responses.

Effects of Dietary Caloric Restriction and Exercise on GLUT 2 in Liver and GLUT-4 and VAMP-2 in Muscle Tissue of Diabetic Rats

  • Jeong, Ilgyu;Oh, Myungjin;Jang, Moonnyeo;Koh, Yunsuk;Biggerstaff, Kyle D.;Nichols, David;Ben-Ezra, Vic
    • Korean Journal of Exercise Nutrition
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    • v.13 no.1
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    • pp.1-7
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    • 2009
  • It has been shown that both caloric restriction and exercise, enhances glucose uptake through translocation of GLUT-4 protein. It remains unclear how exercise and caloric restriction affect the changes in VAMP (vesicle-associated membrane protein) in skeletal muscle and GLUT-2 in liver. This study investigated the effects of exercise training and caloric restriction on the expressions of glucose transport relating proteins in muscle and liver tissues in diabetic rats. Forty male Sprague-Dawley rats (250±10 g; 8 week in age) were assigned equally to four different groups; control (C), exercise only (E), dietary restriction only (D) and dietary restriction and exercise (DE). Daily food consumption was monitored to establish baseline intake. Both C and E groups consumed baseline food intake while D and DE groups were provided with only 60% of baseline total food intake. Forty-eight hours after intraperitoneal injection of STZ (50 mg/kg), diabetes was confirmed (8-hr fasting blood glucose levels ≥300 mg/dl). Rats in the E and DE groups exercised on a motorized treadmill for 30 min/d, 5 days/week for 4 weeks (5 min running at 3 m/min, 0% grade; 8 m/min for the next 5min, and then 15 m/min for 20 min). Rats were sacrificed 48 hrs after the last bout of exercise. Soleus muscle and liver were extracted to analyze for GLUT-4, VAMP-2, and GLUT-2, respectively. All variables were analyzed using the Western Blotting technique. All values were expressed as optical volume measured by optical density. A Two-way ANOVA was used to examine the difference between groups and applied Duncan's test for post-hoc. No significant differences in GLUT-2 expression were found among groups. However, E (280133±13228 arbitrary units{AU}) and DE (268833±14424 AU) groups showed significantly higher (p<.001) levels of GLUT-4 as compared with C (34461±2099 AU) and D groups (27847±703 AU). VAMP-2 protein expression increased (p<.001) in E (184137±7803 AU) and DE (189800±10856 AU) groups as compared to C (74201±8296AU) and D (72967±863 AU) groups. These results suggest that either exercise with or without caloric restriction increases the up-regulation of GLUT-4 and VAMP-2 in skeletal muscle of diabetic rats. However, GLUT-2 protein in liver was not affected by either exercise or exercise with caloric restriction.

Inhibitory Effects of Ssanghwa-tang on Lung Injury and Muscle Loss in a Cigarette Smoke Extract and Lipopolysaccharide-induced Chronic Obstructive Pulmonary Disease Mouse Model (표준담배추출물과 Lipopolysaccharide로 유발한 만성폐쇄성폐질환 동물모델에서 쌍화탕의 폐손상 및 근감소 억제 효과)

  • Jin-kwan Choi;Won-kyung Yang;Su-won Lee;Seong-cheon Woo;Seung-hyung Kim;Yang-chun Park
    • The Journal of Internal Korean Medicine
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    • v.45 no.1
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    • pp.11-30
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    • 2024
  • Objectives: This study evaluated the effects of Ssanghwa-tang (SHT) on lung injury and muscle loss in a COPD mouse model. Methods: C57BL/6 mice were challenged with cigarette smoke extract and lipopolysaccharide, and then treated with two concentrations of SHT (250 and 500 mg/kg). After sacrifice, the bronchoalveolar lavage fluid (BALF) or lung tissue was analyzed by cytospin, ELISA, real-time PCR, flow cytometry analysis, and H&E and Masson's trichrome staining. The grip strength of COPD mice was measured using a grip strength meter. The running time of COPD mice was measured by a treadmill test. Muscle tissue of the quadriceps was stained with H&E and Masson's trichrome staining. Results: SHT significantly inhibited the increase in neutrophil numbers in BALF and significantly decreased immune cell activity in BALF and lung tissue. It also significantly inhibited the increase in TNF-α, IL-17, and MIP2 in BALF. Real-time PCR analysis revealed that the mRNA expression of TNF-α, IL-17, MIP2, and TRPV1 in lung tissue showed a significant decrease compared with the control group. Lung tissue damage was significantly reduced in the histological analysis. The grip strength and running time of the COPD mice showed a significant decrease compared with the control group. In histological staining, SHT was found to reduce the damage to muscle tissue. Conclusions: This study indicates that SHT can be used as a therapeutic agent for COPD patients by inhibiting lung injury and muscle loss.

Case Report: Quantitative Evaluation of Gait Function Following Treatment Progression in a Patient with Central Pontine Myelinolysis (중심성 교뇌수초용해 환자의 치료 경과에 따른 보행 기능의 정량적 평가)

  • Sangho Ji;Sunny Kang;Jiwoo Kim;Youngjo So;Sangkwan Lee;Cheol-Hyun Kim
    • The Journal of Internal Korean Medicine
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    • v.45 no.2
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    • pp.190-198
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    • 2024
  • Introduction: Central pontine myelinolysis (CPM) is a rare neurological disorder marked by symmetric nerve fiber damage, commonly following rapid hyponatremia correction, with no established treatment and a poor prognosis. The condition, often linked to alcoholism, malnutrition, and various diseases, lacks comprehensive studies on its impact on gait. This research aims to quantitatively analyze gait changes in CPM patients receiving both traditional Korean and conventional rehabilitation treatments, addressing a gap in current understanding of CPM management. Case presentation: A 56-year-old male diagnosed with CPM following an initial misdiagnosis underwent combined electoracupuncture and rehabilitative treatment at ○○ university Korean medical center, resulting in significant gait improvements. A treadmill gait analysis system was used to measure changes in key gait parameters at 2-week intervals, and the patient's progress was documented. Conclusions: The quantitative analysis revealed significant gait improvements. Foot rotation decreased from 8.9° to 6.4° (right) and from 11.1° to 7.2° (left); lateral symmetry improved from -7.8 to 0.8; step length increased from 21 cm to 44 cm (right) and from 19 cm to 44 cm (left); and velocity increased from 1.2 m/s to 2.7 m/s. These findings highlight decreased foot rotation and lateral symmetry, along with increased step length and velocity, suggesting a positive outcome of the treatment regimen. Notably, the patient experienced no adverse effects related to the treatments. Despite limitations, including the singe case focus and lack of prior gait-focused CPM research, this case report provides valuable insights into effective CPM management strategies, paving the way for future research in this domain.

Nationwide Trends of Gatekeeper to Invasive Coronary Angiography in Suspected Coronary Artery Disease

  • Min Jae Cha;William D Kim;Hoyoun Won;Jaeeun Joo;Hasung Kim;In-Cheol Kim;Jin Young Kim;Seonhwa Lee;Iksung Cho
    • Korean Circulation Journal
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    • v.52 no.11
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    • pp.814-825
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    • 2022
  • Background and Objectives: Real-world trends in the utility and type of gatekeeping studies in invasive coronary angiography (ICA) requires further investigation. Methods: We identified outpatients who underwent noninvasive cardiac tests or directly ICA for suspected coronary artery disease (CAD) from the nationwide Korea Health Insurance Review and Assessment Service-National Patient Sample database between 2012 and 2018. Results: Among 71,401 patients, the percentage of patients who were evaluated for suspected CAD was 34.7% for treadmill test (TMT), 4.2% for single-photon emission computed tomography (SPECT), 24.2% for coronary computed tomography angiography (CCTA), 1.6% for multiple gatekeepers, and 32.3% for directly ICA without noninvasive studies. The proportion of CCTA as a gatekeeper showed linear increase, (18.6% in 2012 and 28.8% in 2018; p<0.001), while those of TMT, SPECT, and direct ICA have decreased (p<0.001, p=0.03, and p<0.001, respectively). The overall incidence of downstream ICA after gatekeeper was 13.8% (6,662/48,346), and SPECT showed higher ICA rate in pairwise comparison with TMT and CCTA (p<0.001). Patients who performed gatekeepers before ICA showed higher rate of subsequent PCI (34.7% vs. 32.3%; p<0.001) and CABG (3.5% vs. 1.0%; p<0.001), compared to those who directly underwent ICA, and CCTA was associated with higher revascularization rate after ICA in pairwise comparison with TMT and SPECT (p<0.001). Conclusions: Nationwide database demonstrated that CCTA is utilized increasingly as a gatekeeper for ICA and is associated with high revascularization rate after ICA in outpatients with suspected CAD.

Effects of L-Arginine Supplementation and Regular Exercise in D-Galactose Induced Aging Rat Aorta: Study on Inflammatory Factors, Vasodilation Regulatory Factors (노화유도 쥐의 대동맥에서 L-arginine 투여와 규칙적인 운동의 효과: 염증인자와 혈관이완조절 인자의 변화)

  • Lee, Jin;Kwak, Yi-Sub;Yoo, Young-June;Park, Sok
    • Journal of Life Science
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    • v.21 no.10
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    • pp.1415-1421
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    • 2011
  • The purpose of this study was to identify the effects of an L-arginine supplementation and regular exercise training on NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1, eNOS and Ang II in the aortas of D-galactose (D-gal) induced aging rats. The male Strague-Dawley rats were treated with a D-galactose aging inducing agent; the D-gal injection (50 mg/kg) was given intraperitoneally for 12 wk. Experimental groups were divided into five groups: (1) Young control group (Y-Con, n=8), (2) Aging control group (A-Con, n=8), (3) Aging exercise group (A-Ex, n=8), (4) Aging exercise group with L-arginine supplementation group (A-Ex+A, n=8), and (5) Aging with L-arginine supplementation group (A-A, n=8). The exercise consisted of running on a treadmill for 60 min/day at 20 m/min for 6 day/wk, at 0% gradient for 12 wk. The L-arginine supplementation was given orally at a dose of 150 mg/kg/day for 12 wk. The findings of this study were as follows: 1. NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1 and Ang II proteins in the aortas of D-gal induced rats were significantly increased, however, L-arginine supplementation and regular exercise resulted in a significant inhibition in the expression of NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1 and Ang II proteins. 2. eNOS protein in the aortas of D-gal induced rats was significantly decreased, however, L-arginine supplementation and regular exercise resulted in a significant increase in the expression of eNOS proteins. In conclusion, the findings of the present study reveal that L-arginine supplementation alone or regular exercise alone or in combination with L-arginine supplementation for 12 wk increases anti-inflammatory effects by decreasing NF-${\kappa}B$, TNF-${\alpha}$, and iNOS protein expressions within the aortic tissue. In addition, L-arginine supplementation alone or regular exercise alone or in combination with L-arginine supplementation may prevent endothelial function by up-regulation of eNOS protein in the aortas of D-gal induced aging rats.

Effects of Regular Exercise and L-Arginine Intake on Abdominal Fat, GH/IGF-1 Axis, and Circulating Inflammatory Markers in the High Fat Diet-Induced Obese Aged Rat (규칙적인 운동과 L-arginine의 섭취가 고지방식이 유도 비만 노화생쥐의 복부지방량, GH/IGF-1 axis 및 혈관염증지표에 미치는 영향)

  • Park, Sok;Sung, Ki-Woon;Lee, Jin;Lee, Cheon-Ho;Lee, Young-Jun;Yoo, Young-June;Park, Kyoung-Shil;Min, Byung-Jin;Shin, Yong-Sub;Kim, Jung-Suk;Jung, Hun
    • Journal of Life Science
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    • v.22 no.4
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    • pp.516-523
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    • 2012
  • The purpose of this study was to investigate the effect of exercise and/or L-arginine on abdominal fat, IGF-1 on GH/IGF-1 axis, fibrinogen, and PAI-1 in aged and obese rats. Male Sprague-Dawley rats were treated with a D-galactose aging inducing agent (50 mg/kg) given intraperitoneally for 12 weeks. Thirty-two male Sprague-Dawley rats were treated and divided into four groups: aging-high fat diet group (AG+HF), AG+HF with L-arginine intake group (AG+LA), AG+HF with exercise group (AG+EX), and AG+EX with L-arginine intake group (AG+LA+EX). The experimental rats underwent treadmill training (60 min/day, 6 days/week at 0% gradient) for 12 weeks. L-arginine was given orally (150 mg/kg/day) for 12 weeks. After the experiment, blood was collected from the left ventricle and abdominal fat was extracted. The results showed that GH was significantly increased in AG+EX and AG+AL+EX. IGF-1 was significantly increased in both the AG+AL+EX and AG+EX group ($p$<0.05), while fibrinogen and PAI-1 were not significantly different among the groups. Abdominal fat was significantly decreased in the AG+LA, AG+EX, and AG+LA+EX groups ($p$<0.05) compared with the AG+HF group. In conclusion, this study suggests that exercise alone or L-arginine alone or a combination not only increases the GH and IGF-1 concentration, but also decreases the abdominal fat mass.

Assessment of Effect of Pulmonary Rehabilitation on Skeletal Muscle Metabolism by $^{31}P$ Magnetic Resonance Spectroscopy (호흡재활치료 전후 $^{31}P$ 자기공명분석법을 이용한 골격근대사의 변화에 관한 연구)

  • Cho, Won-Kyung;Kim, Dong-Soon;Choe, Kang-Hyeon;Park, Young-Joo;Lim, Tae-Hwan;Shim, Tae-Sun;Lim, Chae-Man;Lee, Sang-Do;Koh, Youn-Suck;Kim, Woo-Sung;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.5
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    • pp.1040-1050
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    • 1997
  • Pulmonary rehabilitation has been known to improve dyspnea and exercise tolerance in patients with chronic lung disease, although it does not improve pulmonary function. The mechanism of this improvement is not clearly explained till now; however some authors suggested that the improvement in the skeletal muscle metabolism after the rehabilitation could be a possible mechanism. The metabolc changes in skeletal muscle in patients with COPD are characterized by impaired oxidative phosphorylation which causes early activation of anaerobic glycolysis and excess lactate production with exercise. In order to evaluate the change in the skeletal muscle metabolism as a possible cause of the improvement in the exercise tolerance after the rehabilitation, noninvasive $^{31}P$ magnetic resonance spectroscopy(MRS) of the forearm flexor muscle was performed before and after the exercise training in nine patients with chronic lung disease who have undertaken intensive pulmonary rehabilitation for 6 weeks. 31p MRS was studied during the sustained isometric contraction of the dominant forearm flexor muscles up to the exhaustion state and the recovery period. Maximal voluntary contraction(MVC) force of the muscle was measured before the isometric exercise, and then 30% of MVC force was constantly loaded to each patient during the isometric exercise. After the exercise training, exercise endurance of upper and lower extremities and 6 minute walking distance were significantly increased(p<0.05). There were no differences of baseline intracellular pH (pHi) and inorganic phosphate/phosphocreatine(Pi/PCr). After rehabilitation pHi at the exercise and the exhaustion state showed a significant increase($6.91{\pm}0.1$ to $6.99{\pm}0.1$ and $6.76{\pm}0.2$ to $6.84{\pm}0.2$ respectively, p<0.05). Pi/PCr at the exercise and the recovery rate of pHi and Pi/PCr did not show significant differences. These results suggest that the delayed intracellular acidosis of skeletal muscle may contribute to the improvement of exercise endurance after pulmonary rehabilitation.

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Screening Test for Heart Diseases in the First Grade Elementary School Children in Busan (부산 지역 초등학교 1학년 학생들의 심장질환의 집단검진에 관한 연구)

  • Oh, Jae Min;Park, Hee Ju
    • Clinical and Experimental Pediatrics
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    • v.46 no.5
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    • pp.490-494
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    • 2003
  • Purpose : We'd like to determine the incidence of congenital heart disease and arrhythmia in elementary school children in Busan, and to provide adequate prevention and treatment. Methods : A total of 23,802(male 12,909, female 10,893) 1st grade elementary school children living in Busan were studied. All children were 7-8 years old. We obtained their medical history by questionnaire and checked elecrocardiography(ECG). Subsequent screening tests including a 2nd ECG, chest X-ray, phonocardiogram and CBC for the students who had abnormal findings at the first screening test. The third screening test was done for students who had cardiac murmurs or abnormal ECG findings in the second screening test by echocardiogram, treadmill test and 24-hour Holter monitoring. Results : Among 23,802 children participants, 605(2.54%) had abnormal ECG findings at the first screening test. Q wave abnormality(0.58%) was observed most frequently, and complete right bundle branch block(RBBB)(0.26%), sinus tachycardia(0.24%), right axis deviation(0.22%) and ventricular premature contraction(VPC)(0.21%) followed in order. Four hundred and twenty four children participated in the second ECG screening test. Two hundred and two children(47.6%) had an abnormality such as sinus tachycardia(18.8%), VPC(17.8%), or complete RBBB(17.3%). After completing the third examination including echocardiogram, we couldn't find the students with ventricular tachycardia (VT) or SVT at the third arrhythmia screening test. Conclusion : A high incidence of arrhythmia was found in the 1st grade elementary school children in Busan despite their healthy appearances, although fatal heart diseases were not noted. Early diagnosis, adequate preventative measures and treatment will prevent and decrease the frequency of emergent situations like syncope and sudden death.