• Tuberculosis and Respiratory Diseases
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• v.40 no.3
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• pp.223-235
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• 1993

Background: Superoxide anion which was produced by macrophage and neutrophil has a defensive role to kill invasive microorganisms and also an injurious role to produce self lung damage. Production of oxygen free radicals including superoxide is a main mechanism of acute lung injury caused by bacterial endotoxin. Endotoxin is known to activate alveolar macrophage to produce increased oxygen free radicals after the stimulation with various biological materials (priming effect). Calcium is a very important intracellular messenger in that cellular process of superoxide production. Method: This experiment was performed to elucidate the effects of endotoxin and calcium on superoxide production by phorbol myristate acetate-stimulated alveolar macrophage and the effect of verapamil on priming effect of endotoxin. Results: 1) Preincubation of macrophages with endotoxin (E. coli 055-B5) primed the cells to respond with increased superoxide production after the stimulation with PMA. Priming with endotoxin ($10^{-1}$ug/ml) produced a maximal enhancement of superoxide production (43%). 2) Verapamil could inhibit the superoxide production by PMA stimulated macrophage regardless of the presence of extracellular calcium. This means that the inhibitory effect of verapamil is caused by a mechanism independent of blocking calcium influx. 3) Verapamil could inhibit the priming effect of endotoxin on alveolar macrophage (from 30% increment to 13% increment) and could inhibit the superoxide production by PMA-stimulated macrophage preincubated with endotoxin. Conclusion: We concluded that verapamil could inhibit the superoxide production by PMA-stimulated rat alveolar macrophage and also inhibit the priming effect of endotoxin on alveolar macrophage. These inhibitory effects of verapamil could be one of the mechanisms of verapamil effects on endotoxin induced lung injury.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.

• Journal of Life Science
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• v.28 no.4
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• pp.435-443
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• 2018

AMP-activated protein kinase (AMPK) functions as a metabolic master through regulating and restoring cellular energy balance. In skeletal muscle, AMPK increases myofibril protein degradation through the expression of muscle-specific ubiquitin ligases. Mori Folium, the leaf of Morus alba, is a traditional medicinal herb with various pharmacological functions; however, the effects associated with muscle atrophy have not been fully identified. In this study, we confirmed the effects of AMPK activation by examining the effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, on the induction of atrophy and expression of atrophy-related genes in C2C12 myotubes. We also investigated the effects of the ethanol extract of Mori Folium (EEMF) on the recovery of AICAR-induced muscle atrophy in C2C12 myotubes. It was found that exposure to AICAR resulted in the stimulation of Forkhead box O3a (FOXO3a); an up-regulation of muscle-specific ubiquitin ligases such as Muscle Atrophy F-box (MAFbx)/atrogin-1 and muscle RING finger-1 (MuRF1), and a down-regulation of muscle-specific transcription factors, such as MyoD and myogenin; with the activation of AMPK. In addition, AICAR without cytotoxicity indicated a decrease in diameter of C2C12 myotubes. However, treatment with EEMF significantly suppressed AICAR-induced muscle atrophy of C2C12 myotubes in a dose-dependent manner as confirmed by a decrease in myotube diameter, which is associated with a reversed stimulation of FOXO3a by the inhibition of AMPK activation. These results indicate that the activation of AMPK by AICAR induces muscle atrophy, and EEMF has preeminent effects on the inhibition of AICAR-induced muscle atrophy through the AMPK signaling pathway.

• Journal of Life Science
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• v.28 no.1
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• pp.26-36
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• 2018

This study was performed to identify the antioxidant and ${\alpha}$-glucosidase inhibitory activities of water and 70% ethanol extracts of the three following herbs: G. procumbens, M. charantia, and C. longa. In addition, the antioxidant and antidiabetic activities of five types of Jerusalem artichoke composites (JA1 - 5), which were prepared by adding ethanol extracts of several herbs to Jerusalem artichoke concentrate, were studied and compared. The results showed that the total phenol and flavonoid contents of the ethanol extracts were higher than those of the water extracts. The DPPH and ABTS radical scavenging activities and reducing power depended on the total phenol and flavonoid contents. The antioxidant activities of ethanol extracts from G. procumbens and C. longa were comparable. Moreover, the ${\alpha}$-glucosidase inhibitory activity of the ethanol extracts ($2,000{\mu}g/ml$) from each herb was found to be over 50%. In contrast, the five types of JA composites showed higher total phenol and flavonoid contents than those of JA concentrate. In addition, increased antioxidant and ${\alpha}$-glucosidase inhibitory activities were observed, with that of JA1 being the highest. However, all concentrations ($1{\sim}100{\mu}g/ml$) of JA tested did not affect the cell viability of Chang cells. In addition, JA induced the activation of AMP-activated protein kinase (AMPK) in Chang cells and significantly increased the glucose uptake in C2C12 cells. Therefore, it could be concluded that the JA composites (JA1 - 5) mixed with G. procumbens, M. charantia, and C. longa extracts were effective in increasing the extracts' antioxidant and antidiabetic activities.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.9
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• pp.1257-1264
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• 2016

Extracts from Artemisia annua $Linn\acute{e}$ (AAE) have various functions (anti-malaria, anti-virus, and anti-oxidant). However, the mechanism of the effects of AAE is not well known. Thus, we determined the apoptotic effects of AAE in AGS human gastric carcinoma cells. In this study, we suggested that AAE may exert cancer cell apoptosis through the Akt/mammalian target of rapamycin (mTOR)/glycogen synthase kinase (GSK)-$3{\beta}$ signal pathway and mitochondria-mediated apoptotic proteins. Activation by Akt phosphorylation resulted in cell proliferation through phosphorylation of tuberous sclerosis complex 2 (TSC2), mTOR, and GSK-$3{\beta}$. Thus, de-phosphorylation of Akt inhibited cell proliferation and induced apoptosis through inhibition of Akt, mTOR, phosphorylation of GSK-$3{\beta}$ at serine9, and control of Bcl-2 family members. Inhibition of GSK-$3{\beta}$ attenuated loss of mitochondrial membrane potential and release of cytochrome C. Bax and pro-apoptotic proteins were activated by their translocation into mitochondria from the cytosol. Translocation of Bax induced outer membrane transmission and generated apoptosis through cytochrome C release and caspase activity. We also measured 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase assay, Hoechst 33342 staining, Annexin V-PI staining, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide staining, and Western blotting. Accordingly, our study showed that AAE treatment to AGS cells resulted in inhibition of Akt, TSC2, GSK-$3{\beta}$-phosphorylated, Bim, Bcl-2, and pro-caspase 3 as well as activation of Bax and Bak expression. These results indicate that AAE induced apoptosis via a mitochondrial event through regulation of the Akt/mTOR/GSK-$3{\beta}$ signaling pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2159-2164
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• 2016

Background: A diagnosis of chronic myeloid leukemia (CML) is made on discovery of the presence of a Philadelphia (Ph) chromosome. The success of the treatment of this form of leukemia with tyrosine kinase inhibitor (TKI) is monitored by reduction of the Ph chromosome. Objective: To compare the role of conventional cytogenetic (CC) methods with a real time quantitative polymerase chain reaction (RQ-PCR) and fluorescence in situ hybridization (FISH) for diagnosis and treatment monitoring of CML patients. The secondary outcome was to analyze the treatment responses to TKI in CML patients. Materials and Methods: This was a retrospective study of CML patients who attended the Hematology clinic at Chiang Mai University Hospital from 2005-2010. Medical records were reviewed for demographic data, risk score, treatment response and the results of CC methods, FISH and RQ-PCR. Results: One hundred and twenty three cases were included in the study, 57.7% of whom were male with a mean age of 46.9 years. Most of the patients registered as intermediate to high risk on the Sokal score. At diagnosis, 121 patients were tested using the CC method and 118 (95.9%) were identified as positive. Five patients failed to be diagnosed by CC methods but were positive for BCR-ABL1 using the FISH method. Imatinib was the first-line treatment used in 120 patients (97.6%). In most patients (108 out of 122, 88.5%), a complete cytogenetic response (CCyR) was achieved after TKI therapy and in 86 patients (70.5%) CCyR was achieved long term by the CC method. Five out of the 35 analyzed patients in which CCyR was achieved by the CC method had a positive FISH result. Out of the 76 patients in which CCyR was achieved, RQ-PCR classified patients to only CCyR in 17 patients (22.4%) with a deeper major molecular response (MMR) in 4 patients (5.3%) and complete molecular response (CMR) in 55 patients (72.4%). In the case of initial therapy, CCyR was achieved in 95 patients (79.1%) who received imatinib and in both patients who received dasatinib (100%). For the second line treatment, nilotinib were used in 30 patients and in 19 of them (63.3%) CCyR was achieved. In half of the 6 patients (50%) who received dasatinib as second line or third line treatment CCyR was also achieved. Conclusions: CML patients had a good response to TKI treatment. FISH could be useful for diagnosis in cases where CC analysis failed to detect the Ph chromosome. RQ-PCR was helpful in detecting any residual disease and determining the depth of the treatment response at levels greater than the CC methods.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.2
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• pp.224-230
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• 2014

Marine algae have long been recognized as a health and beauty food, based on its anti-tumor, anti-inflammatory and anti-obesity activities. In this study, methanol extracts were prepared from 10 different phaeophyta, after which DPPH radical scavenging and cytoprotective activities of HT-22 cells against ${\beta}$-amyloid protein ($A{\beta}$), which has neurotoxic effects, were investigated. In DPPH experiments, Ecklonia cava and Ishige okamurai showed strong ROS scavenging activities, whereas eight other phaeophyta including Petalonia binghamiae (P. bin) showed weak ROS scavenging activities. To validate the cytoprotective effects of 10 different phaeophyta in $A{\beta}$-induced HT-22 cells, protein expression levels of APP, BACE1, iNOS, phosphorylated ERK1/2, phosphorylated p38 and phosphorylated JNK1/2 were determined along with MTT assay. In the MTT assay, P. bin showed the best effective cytoprotective activity at a concentrations of $25{\mu}g/mL$, whereas Sargassum confusum, Colpomenia sinuosa, Myelophycus simplex, and Sargassum hemiphyllum showed potential. Determination of protein expression levels related to $A{\beta}$-induced neurotoxicity in the five selected phaeophyta showed that P. bin inhibited BACE1 and iNOS expression in $A{\beta}$-induced HT-22 cells. These results indicate that the cytoprotective effects of P. bin are mediated by suppressing the pathways involving $A{\beta}$-induced ERK and p38 activation.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.4
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• pp.467-475
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• 2015

Improvement for carcass traits related to beef quality is the key concern in beef production. Recent reports found that epigenetics mediates the interaction of individuals with environment and nutrition. The present study was designed to analyze the genetic effect of single nucleotide polymorphisms (SNPs) in seven epigenetic-related genes (DNMT1, DNMT3a, DNMT3b, DNMT3L, Ago1, Ago2, and HDAC5) and two meat quality candidate genes (CAPN1 and PRKAG3) on fourteen carcass traits related to beef quality in a Snow Dragon beef population, and also to identify SNPs in a total of fourteen cattle populations. Sixteen SNPs were identified and genotyped in 383 individuals sampled from the 14 cattle breeds, which included 147 samples from the Snow Dragon beef population. Data analysis showed significant association of 8 SNPs within 4 genes related to carcass and/or meat quality traits in the beef populations. SNP1 (13154420A>G) in exon 17 of DNMT1 was significantly associated with rib-eye width and lean meat color score (p<0.05). A novel SNP (SNP4, 76198537A>G) of DNMT3a was significantly associated with six beef quality traits. Those individuals with the wild-type genotype AA of DNMT3a showed an increase in carcass weight, chilled carcass weight, flank thicknesses, chuck short rib thickness, chuck short rib score and in chuck flap weight in contrast to the GG genotype. Five out of six SNPs in DNMT3b gene were significantly associated with three beef quality traits. SNP15 (45219258C>T) in CAPN1 was significantly associated with chuck short rib thickness and lean meat color score (p<0.05). The significant effect of SNP15 on lean meat color score individually and in combination with each of other 14 SNPs qualify this SNP to be used as potential marker for improving the trait. In addition, the frequencies of most wild-type alleles were higher than those of the mutant alleles in the native and foreign cattle breeds. Seven SNPs were identified in the epigenetic-related genes. The SNP15 in CAPN1 could be used as a powerful genetic marker in selection programs for beef quality improvement in the Snow Dragon Beef population.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.2
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• pp.199-204
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• 2006

This study was conducted to investigate the quality characteristics of noodles prepared with the addition of nanofiltered (NF) powder of sunmul. Noodles were prepared with different levels $(0\%,\;1.5\%,\;3\%\;and\;5\%,\;w/w)$ of NF powder and physico-chemical properties were examined. Results of rapid visco analyzer showed that peak, trough, final viscosity and set back decreased as the NF powder level increased. The weight and volume of cooked noodles increased with the addition of NF powder. Turbidity of soup also increased as the amount of NF powder increased, indicating higher cooking loss. The color of wet and cooked noodles became greenish yellow as the NF powder level increased. Hardness, springiness, gumminess and brittleness of cooked noodles decreased with the increasing amount of NF powder. Results of sensory evaluation showed that noodles prepared with up to $3\%$ addition of NF powder was considered to be as acceptable as noodles prepared without NF powder.