• Title/Summary/Keyword: CK1

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Ginsenoside Rb1 and compound K improve insulin signaling and inhibit ER stress-associated NLRP3 inflammasome activation in adipose tissue

  • Chen, Weijie;Wang, Junlian;Luo, Yong;Wang, Tao;Li, Xiaochun;Li, Aiyun;Li, Jia;Liu, Kang;Liu, Baolin
    • Journal of Ginseng Research
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    • v.40 no.4
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    • pp.351-358
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    • 2016
  • Background: This study was designed to investigate whether ginsenoside Rb1 (Rb1) and compound K (CK) ameliorated insulin resistance by suppressing endoplasmic reticulum (ER) stress-induced inflammation in adipose tissue. Methods: To induce ER stress, epididymal adipose tissue from mice or differentiated 3T3 adipocytes were exposed to high glucose. The effects of Rb1 and CK on reactive oxygen species production, ER stress, TXNIP/NLRP3 inflammasome activation, inflammation, insulin signaling activation, and glucose uptake were detected by western blot, emzyme-linked immunosorbent assay, or fluorometry. Results: Rb1 and CK suppressed ER stress by dephosphorylation of $IRE1{\alpha}$ and PERK, thereby reducing TXNIP-associated NLRP3 inflammasome activation in adipose tissue. As a result, Rb1 and CK inhibited IL-$1{\beta}$ maturation and downstream inflammatory factor IL-6 secretion. Inflammatory molecules induced insulin resistance by upregulating phosphorylation of insulin receptor substrate-1 at serine residues and impairing insulin PI3K/Akt signaling, leading to decreased glucose uptake by adipocytes. Rb1 and CK reversed these changes by inhibiting ER stress-induced inflammation and ameliorating insulin resistance, thereby improving the insulin IRS-1/PI3K/Akt-signaling pathway in adipose tissue. Conclusion: Rb1 and CK inhibited inflammation and improved insulin signaling in adipose tissue by suppressing ER stress-associated NLRP3 inflammation activation. These findings offered novel insight into the mechanism by which Rb1 and CK ameliorate insulin resistance in adipose tissue.

Diagnostic Efficiency of Lactate Dehydrogenase, Creatine Kinase and Troponin T in Acute Myocardial Infarction (심근 손상에 있어서 Lactate Dehydrogenase, Creatine Kimase 및 Troponin T 진단적 유용성 비교)

  • Lee, Chae-Hoon;Kim, Kyung-Dong;Kim, Chung-Sook
    • Journal of Yeungnam Medical Science
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    • v.12 no.1
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    • pp.48-55
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    • 1995
  • The present study was designed to evaluate the efficiency of total lactate dehydrogenase, total creatine kinase, LD1/LD2 ratio, CK-MB and newly developed troponin T in acute myocardial infarction. The level of troponin T was $0.01{\pm}0.02{\mu}g/L$ in 34 healthy person, but the peak vaule of acute myocardial infarction ranged in 4.7-24.2 ${\mu}g/L$. Total lactate dehydrogenase was peaked in 1 to 3 days after chest pain and then progressively decreased, but LD1/LD2 ratio was persistently higher than 1.0 for 10 days in most patients. Total creatine kinase and CK-MB were peaked in 1-2 days, and normalized in 3-4 days, so they were useful in early diagnosis of acute myocardial infarction, but not for the late stages of acute myocardial infarction. Troponin T is early elevated and persistently high level for more than 10 days. Comparing with total lactate dehydrogenase, total creatine kinase, LD1/LD2 ratio and CK-MB, troponin-T test improves the efficiency of serodiagnostic method for the detection of ischemic myocardial damage.

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A Bacterial Metabolite, Compound K, Induces Programmed Necrosis in MCF-7 Cells via GSK3β

  • Kwak, Chae Won;Son, Young Min;Gu, Min Jeong;Kim, Girak;Lee, In Kyu;Kye, Yoon Chul;Kim, Han Wool;Song, Ki-Duk;Chu, Hyuk;Park, Byung-Chul;Lee, Hak-Kyo;Yang, Deok-Chun;Sprent, Jonathan;Yun, Cheol-Heui
    • Journal of Microbiology and Biotechnology
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    • v.25 no.7
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    • pp.1170-1176
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    • 2015
  • Ginsenosides, the major active component of ginseng, are traditionally used to treat various diseases, including cancer, inflammation, and obesity. Among these, compound K (CK), an intestinal bacterial metabolite of the ginsenosides Rb1, Rb2, and Rc from Bacteroides JY-6, is reported to inhibit cancer cell growth by inducing cell-cycle arrest or cell death, including apoptosis and necrosis. However, the precise effect of CK on breast cancer cells remains unclear. MCF-7 cells were treated with CK ($0-70{\mu}M$) for 24 or 48 h. Cell proliferation and death were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Changes in downstream signaling molecules involved in cell death, including glycogen synthase kinase $3\beta$ ($GSK3\beta$), $GSK3\beta$, $\beta$-catenin, and cyclin D1, were analyzed by western blot assay. To block $GSK3\beta$ signaling, MCF-7 cells were pretreated with $GSK3\beta$ inhibitors 1 h prior to CK treatment. Cell death and the expression of $\beta$-catenin and cyclin D1 were then examined. CK dose- and time-dependently inhibited MCF-7 cell proliferation. Interestingly, CK induced programmed necrosis, but not apoptosis, via the $GSK3\beta$ signaling pathway in MCF-7 cells. CK inhibited $GSK3\beta$ phosphorylation, thereby suppressing the expression of $\beta$-catenin and cyclin D1. Our results suggest that CK induces programmed necrosis in MCF-7 breast cancer cells via the $GSK3\beta$ signaling pathway.

Effects of branched-chain amino acid supplement on knee peak torque and indicators of muscle damage following isokinetic exercise-induced delayed onset muscle soreness

  • Lim, In-Soo
    • Korean Journal of Exercise Nutrition
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    • v.24 no.4
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    • pp.28-33
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    • 2020
  • [Purpose] This study aimed to investigate the effects of branched-chain amino acid (BCAA) supplement on delayed onset muscle soreness (DOMS) by analyzing the maximum muscle strength and indicators of muscle damage. [Methods] Twelve men with majors in physical education were assigned to the BCAA group and placebo group in a double-blinded design, and repeated measurements were conducted. DOMS was induced with an isokinetic exercise. Following BCAA administration, the changes in the knee extension peak torque, flexion peak torque, aspartate aminotransferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH) concentrations were analyzed. The maximum knee muscle strength was measured at the baseline (pre-D0) following BCAA administration for 5 days before exercise (-D5, -4D, -3D, -2D, -1D). In contrast, the post-treatment measurements (D3) were recorded after BCAA administration for 3 days (post-D0, D1, D2). Blood samples were obtained before (pre-D0), immediately after (post-D0), 24 h (D1), 48 h (D2), and 72 h (D3) after the exercise to analyze the indicators of muscle strength. BCAA was administered twice daily for 8 days (5 days and 3 days before inducing DOMS and during the experimental period, respectively). [Results] There was no difference in the flexion peak torque between the groups. However, the BCAA group showed a significantly higher extension peak torque at D3 (second isokinetic exercise), compared to the placebo group (p<.05). There was no difference in AST changes between the groups. Nonetheless, the CK and LDH were significantly reduced in the BCAA group, compared to the placebo group. There was no correlation between the extension peak torque and flexion peak torque. However, the CK and LDH increased proportionately in DOMS. Moreover, their concentrations significantly increased with a decreasing peak torque (p<.01). [Conclusion] An exercise-induced DOMS results in a decrease in the peak torque and a proportional increase in the CK and LDH concentrations. Moreover, the administration of BCAA inhibits the reduction of the extension peak torque and elevation of CK and LDH concentrations. Therefore, BCAA might be administered as a supplement to maintain the muscle strength and prevent muscle damage during vigorous exercises that may induce DOMS in sports settings.

DETERMINATIONS OF ITS ABSOLUTE DIMENSIONS AND DISTANCE BY THE ANALYSES OF LIGHT AND RADIAL-VELOCITY CURVES OF THE CONTACT BINARY - II. CK Bootis (접촉쌍성의 광도와 시선속도곡선의 분석에 의한 절대 물리량과 거리의 결정-II. CK Bootis)

  • Lee, Jae-Woo;Lee, Chung-Uk;Kim, Chun-Hwey;Kang, Young-Beom;Koo, Jae-Rim
    • Journal of Astronomy and Space Sciences
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    • v.21 no.4
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    • pp.275-282
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    • 2004
  • We completed the light curves of the contact binary CK Boo for 13 nights from June to July in 2004 using the 1-m reflector and BVR filters at Mt. Lemmon Optical Astronomy Observatory, and determined four new times of minimum light (three timings for primary eclipse, one for secondary). With contact mode of the 1998-version Wilson-Devinney binary model, we analyzed our BVR light curves and Rucinski & Lu (1999)'s radial-velocity ones. As a result, we found CK boo to be A-type over-contact binary ($f=84\%$) with the low mass ratio (q=0.11) and orbital inclination ($i=65^{\circ}$). Absolute dimensions of the system are determined from our new solution; $M_1=1.42Me{\odot},\;M_2=0.15M{\odot},\;R_1=1.47R{\odot},\;R_2=0.59M{\odot}$ and the distance to it is derived as about 129pc. Our distance is well consistent with that ($157{\pm}33pc$) from the Hipparcos trigonometric parallax within the limit of the error yielded by the latter.

The Diagnostic Utility of Mesothelial Markers in Distinguishing between Reactive Mesothelial Cell and Adenocarcinoma Cells in Serous Effusions with Cytospin Preparation (장액성 삼출액의 도말 표본에서 반응성 중피세포와 샘암종 세포의 감별에 중피세포 표지자의 유용성)

  • Kang, Mi-Sun;Choi, Soo-Im
    • The Korean Journal of Cytopathology
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    • v.17 no.2
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    • pp.108-115
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    • 2006
  • Evaluation of serous effusions can include immunocytochemical stains that differentiate reactive mesothelial cell from adenocarcinoma cell. Among several positive mesothelial cell markers, we used desmin, CK5/6, WT1 and calretinin all known to have high sensitivity and specificity as selective mesothelial cell markers. We studied smears obtained with cytospin from 15 malignant and eight benign effusions. The mesothelial cells were positively stained by desmin, CK5/6, WT1 and calretinin in 60.9%, 29.1%, 26.7% and 56.5%, respectively among 8 benign and 15 malignant effusions; the adenocarcinoma cells were positively stained 6.7%, 13.3%, 1.0% and 0.0%, respectively among 15 malignant effusions. The percentage of positively stained mesothelial cells were somewhat lower for all antibodies compared to the results of previous studies. This was likely due to the differences in preparation methods and fixatives among studies. In conclusion, the use of desmin and calretinin were more valuable than CK5/6 and WT1 for distinguishing between reactive mesothelial cell and adenocarcinoma cells in serous effusion; however, choice of the proper preparation methods and fixatives are also important

Effects of Cheonggukjane on Lipid Metabolism in Hyperlipidemic Female Rats (고지방 섭취 암쥐에 청국장이 지질대사에 미치는 영향)

  • Koh Jin-Bog
    • Journal of Nutrition and Health
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    • v.39 no.4
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    • pp.331-337
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    • 2006
  • The effects of cheonggukjang(traditional fermented soybean food, CK) and cheonggukjang added Agaricus blazei (CKA) on lipid metabolism were investigated in female Sprague-Dawley rats (20 weeks old). The rats were fed a purified hyperlipidemic diet (control diet: 0.1% cholesterol, 10% fat, 18% casein) for 4 weeks. The rats were randomly assigned to each treatment group: control, two kinds of CK or CKA (powders of CK or CKA as dietary protein sources). After 8 weeks of experimental diets consumption, the body weights, and the uterine fat pad weights of CK and CKA diets groups were more significantly decreased than those of the control diet group. The liver cholesterol and triglyceride levels were significantly lower in both the CK and CKA diets groups than those in the control group. The concentrations in serum triglyceride, total cholesterol, LDL-cholesterol, and atherogenic index ratios were significantly decreased in the CK and CKA diets group s compared with those in the control group. The HDL-cholesterol/total-cholesterol ratios were significantly increased in the CK and CKA diets groups compared with those in the control group. The fecal cholesterol and triglyceride excretion in the CK and CKA diets groups were more increased than those in the control group. These results showed that both the feeding the rats with cheonggukjang and cheonggukjang added Agaricus blazei decreased the triglyceride, total cholesterol and LDL-cholesterol in serum as well as the triglyceride and cholesterol in liver, and increased the HDL-cholesterol/total-cholesterol ratio in serum.

Compound K attenuates stromal cell-derived growth factor 1 (SDF-1)-induced migration of C6 glioma cells

  • Kim, Hyuck;Roh, Hyo Sun;Kim, Jai Eun;Park, Sun Dong;Park, Won Hwan;Moon, Jin-Young
    • Nutrition Research and Practice
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    • v.10 no.3
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    • pp.259-264
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    • 2016
  • BACKGROUND/OBJECTIVES: Stromal cell-derived growth factor 1 (SDF-1), also known as chemokine ligand 12, and chemokine receptor type 4 are involved in cancer cell migration. Compound K (CK), a metabolite of protopanaxadiol-type ginsenoside by gut microbiota, is reported to have therapeutic potential in cancer therapy. However, the inhibitory effect of CK on SDF-1 pathway-induced migration of glioma has not yet been established. MATERIALS/METHODS: Cytotoxicity of CK in C6 glioma cells was determined using an EZ-Cytox cell viability assay kit. Cell migration was tested using the wound healing and Boyden chamber assay. Phosphorylation levels of protein kinase C $(PKC){\alpha}$ and extracellular signal-regulated kinase (ERK) were measured by western blot assay, and matrix metallopeptidases (MMP) were measured by gelatin-zymography analysis. RESULTS: CK significantly reduced the phosphorylation of $PKC{\alpha}$ and ERK1/2, expression of MMP9 and MMP2, and inhibited the migration of C6 glioma cells under SDF-1-stimulated conditions. CONCLUSIONS: CK is a cell migration inhibitor that inhibits C6 glioma cell migration by regulating its downstream signaling molecules including $PKC{\alpha}$, ERK1/2, and MMPs.

Purification and Properties of a Novel ${\beta}$-Glucosidase, Hydrolyzing Ginsenoside Rb1 to CK, from Paecilomyces Bainier

  • Yan, Qin;Zhou, Xin-Wen;Zhou, Wei;Li, Xing-Wei;Feng, Mei-Qing;Zhou, Pei
    • Journal of Microbiology and Biotechnology
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    • v.18 no.6
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    • pp.1081-1089
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    • 2008
  • A novel ginsenoside-hydrolyzing ${\beta}$-glucosidase was purified from Paecilomyces Bainier sp. 229 by a combination of Q-Sepharose FF, phenyl-Sepharose CL-4B, and CHT ceramic hydroxyapatite column chromatography. The purified enzyme was a monomeric protein with a molecular mass estimated to be 115 kDa. The optimal enzyme activity was observed at pH 3.5 and $60^{\circ}C$. It was highly stable within pH 3-9 and at temperatures lower than $55^{\circ}C$. The enzyme was specific to ${\beta}$-glucoside. The order of enzyme activities against different types of ${\beta}$-glucosidic linkages was ${\beta}$-(1-6)>${\beta}$-(1-2)>${\beta}$-(1-4). The enzyme converted ginsenoside Rb1 to CK specifically and efficiently. An 84.3% amount of ginsenoside Rb1, with an initial concentration of 2 mM, was converted into CK in 24 h by the enzyme at $45^{\circ}C$ and pH 3.5. The hydrolysis pathway of ginsenoside Rb1 by the enzyme was $Rb1{\to}Rd{\to}F2{\to}CK$. Five tryptic peptide fragments of the enzyme were identified by a newly developed de novo sequencing method of post-source decay (PSD) matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. By comparing the five identified peptide sequences with the NCBI database, this purified ${\beta}$-glucosidase proves to be a new protein that has not been reported before.

Changes of Serum Troponin-T Concentrations in Patients with Open Heart Surgery (개심술환자에 있어 혈청 Troponin-T 농도의 변화에 관한 연구)

  • 박동욱;최석철;김윤규;박종원;조관현
    • 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.

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