• Title/Summary/Keyword: CK5/6

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Compound K attenuates hyperglycemia by enhancing glucagon-like peptide-1 secretion through activating TGR5 via the remodeling of gut microbiota and bile acid metabolism

  • Tian, Fengyuan;Huang, Shuo;Xu, Wangda;Chen, Lan;Su, Jianming;Ni, Haixiang;Feng, Xiaohong;Chen, Jie;Wang, Xi;Huang, Qi
    • Journal of Ginseng Research
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    • v.46 no.6
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    • pp.780-789
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    • 2022
  • Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.

A Clinical Evaluation of Spontaneous Pneumothorax; A Review of 612 Cases (자연기흉의 임상적 고찰)

  • 황석하
    • Journal of Chest Surgery
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    • v.26 no.11
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    • pp.866-870
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    • 1993
  • Possible enhancement of myocardial protection with oxygenated crystalloid cardioplegia and blood cardioplegia were evaluated in a cardiac enzyme study. The bicarbonate-containing solution equilibrated with 100% oxygen becomes highly alkaline as carbon dioxide is released. 95% oxygen and 5% carbon dioxide was added to the crystalloid cardioplegic solution [St. Thomas` Hospital No. 2 Solution] for prevention of severe alkalinity of oxygenated crystalloid cardioplegia. Heart was arrested and reinfused every 20 minutes throughtout the ischemic period with crystalloid cardioplegia or oxygenated crystalloid cardioplegia or blood cardioplegia. Group I was a patient with crystalloid cardioplegia in 11 patients. Group II was a patient with oxygenated crystalloid cardioplegia in 9 patients. Group III was a patient with blood cardioplegia in 15 patients. The value of CK-MB was evaluated from the patient`s serum at 6 hours, 24 hours, and 48 hours postoperatively. In Group I and II, there was no significant change of CK-MB. In Group I and III, the value of CK-MB at postoperative 6 hours was 114$\pm$83 ng/ml and 56$\pm$22 ng/ml [P < 0.05]. In conclusion, blood cardioplegia was superior to crystalloid cardioplegia.

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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.

Effects of the Administration of p-{N ,N-Bis(2-chloroethyl)amino}-4-phenyl acetyl-amino-2,6-piperidinedione (ck-15) on Rat Kidney

  • Park, Sun-Hee;Choi, Bo-Kil;Lim, Dong-Koo;,
    • Toxicological Research
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    • v.14 no.3
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    • pp.365-370
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    • 1998
  • To evaluate the renal toxicity of the antitumor agent, p-{N,N,-Bis(2-chloroethyl)amino}-4-phenyl acetyl-amino-2,6-piperidinedione(CK-15), rats were treated with CK-15 (acute: 50mg/kg. i.p., single and subacute: 5mg/kg, i.p., daily for 7 days). The changes in the body weight, water consumption, kidney weights and urine volume after and during the treatment were observed. The concentrations of urinary creatinine and portein, the activities of N-acetyl-${\beta}$-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), ${\gamma}$-glutamyl transpeptidase (${\gamma}$-GT) and lactate dehydrogenase (LDH) in 24hr urine were also determined. The body weight, water consumption, and urine volume were decreased after the acute and subacute administration. However the weights of kidney were not changed after the treatments. The excretion of creatinine was significantly decreased 1 day after acute administration but, returned to the control value. In subactute administration, the excretion of creatinine was gradually decreased. However, the protein excretion did not changed in both treatment. Those indicate that CK-15 might decrease the metabolic rate of muscle. THe urinary activities of NAG, AAP, ${\gamma}$-GT, and LDH were significantly affected bythe drug treatment. The urinary activities of NAG, AAP and ${\gamma}$-GT were significantly increased 1 day after the acute administration and then returned to the control value. However, the urinary activities of LDH were not changed in acute treatment. In subacute treatment, although the urinary activities of NAG were not changed, those of AAP and ${\gamma}$-GT were significantly increased 2.3 times at 3 days during the subacute administration. Also the urinary activities of LDH were significantly increased at 7 day after the administration. These results indicate that the high and subacute administration might induce a damage in the kidney cells. Furthermore the present results suggest that the toxic effects of CK-15 might be due to the accumulation of the metabolites.

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Studies on Chromosomal Aberration in Korean Native Cattle I. 1/29 Robertsonian Translocation of Korean Native and Crossbred Bulls (한우의 염색체 이상에 관한 연구 I. 한우와 교잡종 수소에서의 1/29 Robertson형 전좌)

  • 김창근;정영채;이근상;김흥률;이장희;정진태
    • Korean Journal of Animal Reproduction
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    • v.15 no.2
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    • pp.87-95
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    • 1991
  • The chromosome analyses of blood culture were made of 11 Korean native and 53 crossbred males between the Korean native cattles(K) and Charolais(C), which consisted of $K\times$K, $C\times$K, $C\times$CK, CK$\times$CCK and Charolais synthetic males(CK$\times$CCK or CCK$\times$CK). 1. The diploid(2n=60, XY) Charolais synthetic male has the 29 pairs of acrocentric autosomes, a single large submetacentric X and a small metacentric Y chromosome. 2. The numbers of G-band of karyotype in these males were a few differences in the 8 pairs of autosomes(chromosome 2, 4, 5, 6, 9, 11, 19 and 26) compared to those of purebred Korean native ones. G-banding qualities were not matched in chromosome 16, 19 and 29 with the Korean native males and also in chromosome 14, 20 and 22 with other domestic cattles. 3. The G-banding pattern between chromosome 4-6-7 and 24-25-27 was alomost similar together and the possibilityof misidentification was greater in the G-banded preparations. 4. 1/29 Robertsonian translocation and other abnormalities were not observed among 11 Korean native and 53 crossbred males. This result is considered in relation to limited data and further investigation based on larger samples may be necessary for definite conclusion.

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Compound K ameliorates airway inflammation and mucus secretion through the regulation of PKC signaling in vitro and in vivo

  • Lee, Jae-Won;Kim, Mun-Ock;Song, Yu Na;Min, Jae-Hong;Kim, Seong-Man;Kang, Myung-Ji;Oh, Eun Sol;Lee, Ro Woon;Jung, Sunin;Ro, Hyunju;Lee, Jae Kyoung;Ryu, Hyung Won;Lee, Dae Young;Lee, Su Ui
    • Journal of Ginseng Research
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    • v.46 no.3
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    • pp.496-504
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    • 2022
  • Background: Cigarette smoke (CS) is considered a principal cause of chronic obstructive pulmonary disease (COPD) and is associated with mucus hypersecretion and airway inflammation. Ginsenoside compound K (CK), a product of ginsenoside metabolism, has various biological activities. Studies on the effects of CK for the treatment of COPD and mucus hypersecretion, including the underlying signaling mechanism, have not yet been conducted. Methods: To study the protective effects and molecular mechanism of CK, phorbol 12-myristate 13-acetate (PMA)-induced human airway epithelial (NCI-H292) cells were used as a cellular model of airway inflammation. An experimental mouse COPD model was also established via CS inhalation and intranasal administration of lipopolysaccharide. Mucin 5AC (MUC5AC), monocyte chemoattractant protein-1, tumor necrosis factor-α (TNF-α), and interleukin-6 secretion, as well as elastase activity and reactive oxygen species production, were determined through enzyme-linked immunosorbent assay. Inflammatory cell influx and mucus secretion in mouse lung tissues were estimated using hematoxylin and eosin and periodic acid-schiff staining, respectively. PKCδ and its downstream signaling molecules were analyzed via western blotting. Results: CK prevented the secretion of MUC5AC and TNF-α in PMA-stimulated NCI-H292 cells and exhibited a protective effect in COPD mice via the suppression of inflammatory mediators and mucus secretion. These effects were accompanied by an inactivation of PKCδ and related signaling in vitro and in vivo. Conclusion: CK suppressed pulmonary inflammation and mucus secretion in COPD mouse model through PKC regulation, highlighting the compound's potential as a useful adjuvant in the prevention and treatment of COPD.

Early Predictive Values for Severe Rhabdomyolysis in Blunt Trauma

  • Park, Jung Yun;Kim, Myoung Jun;Lee, Jae Gil
    • Journal of Trauma and Injury
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    • v.32 no.1
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    • pp.26-31
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    • 2019
  • Purpose: Rhabdomyolysis (RB) is a syndrome characterized by the decomposition of striated muscles and leakage of their contents into the bloodstream. Acute kidney injury (AKI) is the most significant and serious complication of RB and is a major cause of mortality in patients with RB. Severe RB (creatine kinase [CK] ${\geq}5,000$) has been associated with AKI. However, early prediction is difficult because CK can reach peak levels 1-3 days after the trauma. Hence, the aim of our study was to identify predictors of severe RB using initial patient information and parameters. Methods: We retrospectively analyzed 1,023 blunt trauma patients admitted to a single tertiary hospital between August 2011 and March 2018. Patients with previously diagnosed chronic kidney disease were excluded from the study. RB and severe RB were defined as a CK level ${\geq}1,000U/L$ and ${\geq}5,000U/L$, respectively. The diagnosis of AKI was based on RIFLE criteria. Results: The overall incidence of RB and severe RB was 31.3% (n=320) and 6.2% (n=63), respectively. On multivariable analysis, male sex (odds ratio [OR] 3.78, 95% confidence interval [CI] 1.43 to 10.00), initial base excess (OR 0.85, 95% CI 0.80 to 0.90), initial CK (OR 2.07, 95% CI 1.67 to 2.57), and extremity abbreviated injury scale score (OR 1.78, 95% CI 1.39 to 2.29) were found to predict severe RB. The results of receiver operating characteristic analysis showed that the best cutoff value for the initial serum CK level predictive of severe RB was 1,494 U/L. Conclusions: Male patients with severe extremity injuries, low base excess, and initial CK level >1,500 U/L should receive vigorous fluid resuscitation.

Ginsenoside compound K protects human umbilical vein endothelial cells against oxidized low-density lipoprotein-induced injury via inhibition of nuclear factor-κB, p38, and JNK MAPK pathways

  • Lu, Shan;Luo, Yun;Zhou, Ping;Yang, Ke;Sun, Guibo;Sun, Xiaobo
    • Journal of Ginseng Research
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    • v.43 no.1
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    • pp.95-104
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    • 2019
  • Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.

Behaviors of Soft Bangkok Clay behind Diaphragm Wall Under Unloading Compression Triaxial Test (삼축압축 하에서 지중연속벽 주변 방콕 연약 점토의 거동)

  • Le, Nghia Trong;Teparaksa, Wanchai;Mitachi, Toshiyuki;Kawaguchi, Takayuki
    • Journal of the Korean Geotechnical Society
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    • v.23 no.9
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    • pp.5-16
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    • 2007
  • The simple linear elastic-perfectly plastic model with soil parameters $s_u,\;E_u$ and n of undrained condition is usually applied to predict the displacement of a constructed diaphragm wall(DW) on soft soils during excavation. However, the application of this soil model for finite element analysis could not interpret the continued increment of the lateral displacement of the DW for the large and deep excavation area both during the elapsed time without activity of excavation and after finishing excavation. To study the characteristic behaviors of soil behind the DW during the periods without excavation, a series of tests on soft Bangkok clay samples are simulated in the same manner as stress condition of soil elements happening behind diaphragm wall by triaxial tests. Three kinds of triaxial tests are carried out in this research: $K_0$ consolidated undrained compression($CK_0U_C$) and $K_0$ consolidated drained/undrained unloading compression with periodic decrement of horizontal pressure($CK_0DUC$ and $CK_0UUC$). The study shows that the shear strength of series $CK_0DUC$ tests is equal to the residual strength of $CK_0UC$ tests. The Young's modulus determined at each decrement step of the horizontal pressure of soil specimen on $CK_0DUC$ tests decreases with increase in the deviator stress. In addition, the slope of Critical State Line of both $CK_0UC$ and $CK_0DUC$ tests is equal. Moreover, the axial and radial strain rates of each decrement of horizontal pressure step of $CK_0DUC$ tests are established with the function of time, a slope of critical state line and a ratio of deviator and mean effective stress. This study shows that the results of the unloading compression triaxial tests can be used to predict the diaphragm wall deflection during excavation.

Clinical Evaluation of Traumatic Sternal Fracture (외상성 흉골 골절의 임상적 평가)

  • Lee, Sung-Joo;Koo, Won-Mo;Moon, Seong-Cheol;Kim, Dae-Sig;Lee, Gun;Lim, Chang-Young;Kim, Chang-Hoe;Chae, Sung-Soo
    • Journal of Chest Surgery
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    • v.31 no.3
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    • pp.291-297
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    • 1998
  • Sternal fractures, once thought of as an uncommon phenomenon, have occurred with an increasing frequency, paralleling the incidence of motor vehicle accidents. The tremendous force necessary to cause sternal fracture and this bone's prominent position overlying major intrathoracic and mediastinal structures, have important implications in the assessment and treatment of patients. This evaluation is based on the review of 72 patients of traumatic sternal fracture treated at the Department of Thoracic and Cardiovascular Surgery, Seoul Adventist Hospital during the last 4 years from March 1993 to February 1997. The frequency was 12.2% of nonpenetrating chest trauma and average age was 43.2 years old. Automobile accidents(84%) and sternal body fractures(95.8%) with anterior displacements(19.4%) was the most common cause and fracture site. Increase of cardiac isoenzymes was more frequent and higher in sternal fracture than chest contusion but there was no relationship between the time to take normalization of them and the mode of trauma.

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