• Journal of Ginseng Research
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• v.47 no.1
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• pp.106-116
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• 2023

Background: Pirarubicin (THP) is an anthracycline antibiotic used to treat various malignancies in humans. The clinical usefulness of THP is unfortunately limited by its dose-related cardiotoxicity. Ginsenoside F1 (GF1) is a metabolite formed when the ginsenosides Re and Rg1 are hydrolyzed. However, the protective effects and underlying mechanisms of GF1 on THP-induced cardiotoxicity remain unclear. Methods: We investigated the anti-apoptotic and anti-oxidative stress effects of GF1 on an in vitro model, using H9c2 cells stimulated by THP, plus trigonelline or AKT inhibitor imidazoquinoxaline (IMQ), as well as an in vivo model using THP-induced cardiotoxicity in rats. Using an enzyme-linked immunosorbent test, the levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (c-TnT), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione (GSH) were determined. Nuclear factor (erythroid-derived2)-like 2 (Nrf2) and the expression of Nrf2 target genes, including heme oxygenase-1 (HO-1), glutathione-S-transferase (Gst), glutamate-cysteine ligase modifier subunit (GCLM), and expression levels of AKT/Bcl-2 signaling pathway proteins were detected using Western blot analysis. Results: THP-induced myocardial histopathological damage, electrocardiogram (ECG) abnormalities, and cardiac dysfunction were reduced in vivo by GF1. GF1 also decreased MDA, BNP, CK-MB, c-TnT, and LDH levels in the serum, while raising SOD and GSH levels. GF1 boosted Nrf2 nuclear translocation and Nrf2 target gene expression, including HO-1, Gst, and GCLM. Furthermore, GF1 regulated apoptosis by activating AKT/Bcl-2 signaling pathways. Employing Nrf2 inhibitor trigonelline and AKT inhibitor IMQ revealed that GF1 lacked antioxidant and anti-apoptotic effects. Conclusion: In conclusion, GF1 was found to alleviate THP-induced cardiotoxicity via modulating Nrf2 and AKT/Bcl-2 signaling pathways, ultimately alleviating myocardial oxidative stress and apoptosis.

• 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.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.2
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• pp.93-101
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• 2016

Purpose: McArdle disease, glycogen storage disease type V (GSD V), is one of the most common adolescent-onset glycogen storage diseases. It is caused by recessive mutations in PYGM encoding myophosphorylase, which is critical to glycogen metabolism. Since only a few korean patients have been reported, we will observe the clinical and genetic features of three korean patients with McArdle disease. Methods: We retrospectively reviewed the medical records of three patients with genetically confirmed McArdle disease, including the results of forearm ischemic exercise test, electromyogram, nerve conduction velocity, muscle biopsy, and PYGM analysis in peripheral leukocytes. Results: All three cases were males and their age of symptom onset was 12, 5, 14 years old, respectively. A high basal level of serum creatine kinase was noted in all three patients. They experienced the recurrent episodes of rhabdomyolysis, but second wind phenomenon was not definite. In muscle biopsy, subsarcolemmal space vacuoles including periodic acid schiff stained materials were found in two patients, while no evidence of glycogen storage disease was found in the other. A total of five different mutations, $p.Arg50^*$, p.Trp798Arg, $p.Arg50^*$, p.Glu779del, $p.Asp511Thrfs^*28$ and p.Phe710del, were found in three patients. Avoidance of isometric exercise, aerobic exercise and glucose intake before each exercise were recommended for all patients. Conclusion: The three Korean patients with McArdle disease showed the typical manifestations of the condition. The most mutations were private. Therefore, identification of more cases with long-term follow-up will be required to understand the clinical and genetic features of this disease among Korean population.

• Korean Journal of Poultry Science
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• v.36 no.2
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• pp.165-175
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• 2009

Fatty liver-hemorrhagic syndrome (FLHS) is a common nutritional disease in commercial layers and breeders. The most important clinical sign of FLHS is a sudden drop in egg production and increased mortality which causes significant economic loss in the poultry industry. However, the current diagnostic method for FLHS is based on the gross findings at necropsy which is not helpful to reduce the economic loss because of lateness of diagnosis. Therefore, we need early diagnosis and diagnostic methods before chickens were affected by FLHS. In this study we tried to evaluate the effectiveness of clinical pathology including blood chemistry as an early diagnostic method for FLHS in commercial chickens. Profiles of blood biochemistry were compared between two flocks selected in the same commercial layer farm based on the presence of FLHS clinical sings. A flock with clinical signs of FLHS was designated as FLHS and other flock without clinical signs of FLHS as Non-FLHS. Several parameters of blood biochemistry were selected and compared between FLHS and Non-FLHS to evaluate the possibility of early diagnosis. Average concentrations of serum cholesterol, serum calcium, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) were $139.4\;{\pm}\;87.2$ (mg/dL), $24.5\;{\pm}\;5.4$ (mg/dL), $153.6\;{\pm}\;23.1$ (IU/L), $1238.3\;{\pm}\;475.2$ (IU/L) and $1107.3\;{\pm}\;422.8$ (IU/L) in Non-FLHS flock, respectively, and $210.2\;{\pm}\;173.2$ (mg/dL), $25.2\;{\pm}\;4.1$ (mg/dL), $174.3\;{\pm}\;53.5$ (IU/L), $1694.9\;{\pm}\;691.3$ (IU/L) and $1104.9\;{\pm}\;472.9$ (IU/L) in FLHS flock, respectively. The activities of serum cholesterol, AST and LDH except CK, were significantly higher in FLHS than those in Non-FLHS flock (p<0.05). Some birds of FLHS flock showed 2~17 times greater than in Non-FLHS flock. For the definitive diagnosis of FLHS in the flocks tested for blood chemistry, we analyzed fat content and histological lesion score in the liver sampled from both FLHS and Non-FLHS flock. Average liver fat contents based on dry weight were $16.1\;{\pm}\;0.4$ (%) in Non-FLHS flock and were $21.6\;{\pm}\;16.0$ (%) in FLHS flock. These result confirmed that FLHS flock was definitely affected by FLHS. The above results suggest that selected parameters of blood biochemistry, particularly AST, could be useful to diagnose FLHS before significant liver damage occurred in commercial layers.

• Investigative Magnetic Resonance Imaging
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• v.8 no.2
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• pp.94-99
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• 2004

Purpose : To investigate the signal enhancement ratio by NOE effect on in vivo $^{31}P$ MRS in human heart muscle and liver. we also evaluated the enhancement ratios of different phosphorus metabolites, which are important in 31P MRS for each organ. Materials and Methods : Ten normal subjects (M:F = 8:2, age range = 24-32 yrs) were included for in vivo $^{31}P$ MRS measurements on a 1.5 T whole-body MRI/MRS system using $^1H-^{31}P$ dual tuned surface coil. Two-dimensional Chemical Shift Imaging (2D CSI) pulse sequence for $^{31}P$ MRS was employed in all $^{31}P$ MRS measurements. First, $^{31}P$ MRS performed without NOE effect and then the same 2D CSI data acquisitions were repeated with NOE effect. After postprocessing the MRS raw data in the time domain, the signal enhancements in percent were estimated from the major metabolites. Results : The calculated NOE enhancement for liver $^{31}P$ MRS were $\alpha-ATP\;(7\%),\;\beta-ATP\;(9\%),\;\gamma-ATP\;(17\%),\;Pi\;(1\%),\;PDE\;(19\%)$ and $PME\;(31\%)$. Because there is no creatine kinase activity in liver, PCr signal is absent. For cardiac $^{31}P$ MRS, whole body coil gave better scout images and thus better localization than surface coil. In $^{31}P$cardiac multi-voxel spectra, DPG signal increased from left to right according to the amount of blood included. The calculated enhancement for cardiac $^{31}P$ MRS were : $\alpha-ATP\;(12\%),\;\beta-ATP\;(19\%),\;\gamma-ATP\;(30\%),\;PCr\;(34\%),\;Pi\;(20\%),\;(PDE)\;(51\%),\;and\;DPG\;(72\%)$. Conclusion : Our results revealed that the NOE effect was more pronounced in heart muscle than in liver with different coupling to 1H spin system and thus different heteronuclear cross-relaxation.

• Clinical and Experimental Pediatrics
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• v.50 no.9
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• pp.882-890
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• 2007

Purpose : Preterm very low birth weight infant have high rate of adverse neurodevelopmental sequale. Recently, there have been lots of reports that human umbilical cord blood transplantation ameliorates functional deficits in animal models as hypoxic ischemic injury. This pilot study was undertaken to determine the clinical efficacy and safety of autologous umbilical cord blood cell transplantation for preventing neurodevelopmental sequale in perterm VLBW. Methods : Subjects were 26 preterm infants whose birth weight are less than 1,500 g and delivered under the intrauterine period 34 weeks. Autologous umbilical mononuclear cells (about $5.87{\times}10^7/kg$) were injected to neonate via the umbilical vein on the postnatal 24-48 hour. The therapeutic efficacy was assessed by numbers of nucleated RBC, urinary uric acid/creatinine ratio, concentration of neuron specific enolase (NSE), interleukin 6 (IL6), interleukin-$1{\beta}$ ($IL-1{\beta}$), and glial cell derived neurotrophic factor (GDNF) in serum and cerebrospinal fluid on day 1 and 7. Results : There were no significant differences in the numbers of the nucleated RBC, urinary uric acid/creatinine ratio, concentration of creatine kinase between the transplanted infants and controls. But the nucleated RBC is more likely to be rapidly discharged in the transplanted group. In the transplanted group, the concentrations of IL6, $IL-1{\beta}$, and GDNF were no significant difference between day 1 and 7, although GDNF seemed to be elevated. Serum NSE concentration was significantly elevated after transplantation, but not in CSF. Conclusion : It is suggested that autologous umbilical cord blood transplantation in preterm very low birth weight infant is safe to apply clinical practice. Long term follow up study should be needed to evaluate the potential therapeutic effect of umbilical cord blood transplantation for neuroprotection.

• Journal of Chest Surgery
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• v.31 no.2
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• pp.125-133
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• 1998

This study was designed to identify the efficiency of serum troponin-T(s-TnT) level as a diagnostic indicator for the perioperative myocardial damage with open heart surgery(OHS) and to compare with the conventional myocardial enzyme tests such as isoenzyme fraction of creatine kinase(% CK-MB) and isoenzyme ratio of lactate dehydrogenase(LDH1/LDH2 ratio). The study was performed on 30 adult patients who underwent OHS from Jan. 1996 to June 1996 at Inje University Pusan Paik Hospital, and they were divided into two groups accor- ding to aortic clamping time(ACT) duration : group I(ACT＜60 minutes, n=15); group II (ACT＞60 minutes, n=15). S-TnT, % CK-MB, and LDH1/LDH2 ratio were measured in serial blood samples from all subjected patients. The results were obtained as follows. 1. In both groups, s-TnT concentrations increased gradually during OHS and elevated significantly at CPB-10(p＜0.001). The peak level was noticed at POD 1 in group I(1.10 $\pm$0.19 ng/ml), whereas, at CPB-off in group II(1.88$\pm$0.42 ng/ml). The elevated levels remained until POD 7 in both groups. 2. %CK-MB was risen significantly with the initiation of operations(p＜0.001) and the peak levels were noticed at CPB-off in both groups(7.14$\pm$0.86% in group I, 10.69$\pm$1.27% in group II). Thereafter, these levels returned to normal values at POD 3. 3. There were no significant changes in the values of LDH1/LDH2 ratio during and after OHS compared with the control levels(p＞0.05). 4. The serial changes of s-TnT were relatively well correlated with those of changes of % CK-MB(r=0.64, p＜0.05). 5. The serial s-TnT levels were significantly higher in group II than group I from B-ACR to POD 1(p＜0.05), suggesting that duration of aortic clamping time was a major factor concerned with perioperative myocardial injury. In conclusion, measurement of s-TnT is a very useful indicator in assessing the myocardial cell damage and therefore it is expected that serial checking and evaluation of the s-TnT is very available for identification of the perioperative myocardial damage and for postoperative cares in patients with OHS.

• Korean Journal of Poultry Science
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• v.43 no.3
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• pp.149-157
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• 2016

This study was performed to investigate the effects of the stocking density (standard stocking density (SSD, $495cm^2/bird$)) vs. high stocking density (HSD,245cm2/bird) and challenge with lipopolysaccharide (LPS, 5mg/kg BW) on the stress-related physiological indicators in chicks. There was a significant (p<0.05) decrease in body weight, but not in the weight of immune organs, between the SSD and HSD groups. The LPS group resulted in a significant (p<0.05) increase in the weights of the thymus and bursa of fabricius compared with the SSD group. Plasma biochemical components, including aspartate transaminase (AST), alanine transaminase (ALT), blood urea nitrogen, Ca, P, creatine kinase and uric acid, markedly (p<0.05) increased in the LPS birds, although no difference in these parameters was observed between the SSD and HSD birds. Furthermore, the birds challenged with LPS showed a significant (p<0.05) increase in the plasma corticosterone level, although this hormone did not differ between the SSD and HSD groups. In the mRNA expression of pro-inflammatory cytokines, hepatic $IL-1{\beta}$, IL-6 and iNOS in the LPS group significantly (p<0.05) increased compared with those in the SSD group. Thymic mRNA expression of $IL-1{\beta}$, IL-6 and IL-18 in the LPS group also significantly (p<0.05) increased compared with those in the other groups. In addition, mRNA expression of $IL-1{\beta}$ in the bursa of fabricius of the LPS group increased (p<0.05) without affecting the other cytokines. Under high stocking density, thymic $IL-1{\beta}$ was the only cytokine that was up-regulated compared with the SSD group. In conclusion, an acute stress induced by LPS challenge profoundly affected immune organ weight, blood biochemical profiles and pro-inflammatory cytokine expression, while chronic stress did not markedly affect biochemical and immunological parameters, suggesting that chicks under high stocking density could be adapted to prolonged stressors.

• Clinical and Experimental Pediatrics
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• v.45 no.4
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• pp.498-504
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• 2002

Purpose : The purpose of this study was to evaluate the perioperative myocardial damage in pediatric congenital heart disease with the cardiac specific protein of cardiac troponin I(cTpn-I). Methods : All 25 pediatric patients who were diagnosed with tetralogy of Fallot or double outlet right ventricle were classified as group A(acyanotic, $SaO_2$ >90%), group B(mildly cyanotic, $SaO_2$ >80-90%) and group C(moderately cyanotic, $SaO_2$ <80%). The control group D was consisted of 10 patients with ventricular septal defects who were operated in the same period. We measured preoperative hemoglobin, preoperative and postoperative(24 and 72 hour) arterial oxygen saturation, cTpn-I and creatine kinase(CK-MB). Results : Total 25 patients were subdivided into 6 of group A, 12 of group B and 7 of group C. The concentrations of preoperative cTpn-I were $0.23{\pm}0.12ng/mL$ in group A, $0.25{\pm}00.12 ng/mL$ in group B, $0.26{\pm}0.13ng/mL$ in group C. And the concentrations of cTpn-I in postoperative 24 hour were $10.04{\pm}5.28ng/mL$ in group A, $12.50{\pm}6.86ng/mL$ in group B, $12.55{\pm}9.90ng/mL$ in group C. Which revealed cTpn-I in group C was higher than that of the another less cyanotic groups. In addition, the concentration of cTpn-I of group C in postoperative 72 hour was higher than any other groups. The concentration of cTpn-I in postoperative 72 hour was statistically correlated with that in postoperative 24 hour and preoperative arterial oxygen saturation(P=0.001). Conclusion : Preoperative chronic cyanosis can influence on the postoperative concentration of cTpn-I in pediatric cardiac patients, which means impairment on the postoperative myocardial recovery.