• Journal of Ginseng Research
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• v.47 no.3
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• pp.408-419
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• 2023

Background: Ginsenoside compound K (CK), the main active metabolite in Panax ginseng, has shown good safety and bioavailability in clinical trials and exerts neuroprotective effects in cerebral ischemic stroke. However, its potential role in the prevention of cerebral ischemia/reperfusion (I/R) injury remains unclear. Our study aimed to investigate the molecular mechanism of ginsenoside CK against cerebral I/R injury. Methods: We used a combination of in vitro and in vivo models, including oxygen and glucose deprivation/reperfusion induced PC12 cell model and middle cerebral artery occlusion/reperfusion induced rat model, to mimic I/R injury. Intracellular oxygen consumption and extracellular acidification rate were analyzed by Seahorse multifunctional energy metabolism system; ATP production was detected by luciferase method. The number and size of mitochondria were analyzed by transmission electron microscopy and MitoTracker probe combined with confocal laser microscopy. The potential mechanisms of ginsenoside CK on mitochondrial dynamics and bioenergy were evaluated by RNA interference, pharmacological antagonism combined with co-immunoprecipitation analysis and phenotypic analysis. Results: Ginsenoside CK pretreatment could attenuate mitochondrial translocation of DRP1, mitophagy, mitochondrial apoptosis, and neuronal bioenergy imbalance against cerebral I/R injury in both in vitro and in vivo models. Our data also confirmed that ginsenoside CK administration could reduce the binding affinity of Mul1 and Mfn2 to inhibit the ubiquitination and degradation of Mfn2, thereby elevating the protein level of Mfn2 in cerebral I/R injury. Conclusion: These data provide evidence that ginsenoside CK may be a promising therapeutic agent against cerebral I/R injury via Mul1/Mfn2 mediated mitochondrial dynamics and bioenergy.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.3
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• pp.235-245
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• 2008

Purpose: The HSV1-tk gene has been extensively studied as a type of reporter gene. In hepatocellular carcinoma (HCC), only a small proportion of patients are eligible for surgical resection and there is limitation in palliative options. Therefore, there is a need for the development of new treatment modalities and gene therapy is a leading candidate. In the present study, we investigated the usefulness of substrate, 2'-fluoro-2'-deoxy-1-${\beta}$-D-arabino-furanosyi-5-[$^{124/125}I$]iodo- uracil ([$I^{124/125}I$]FIAU) as a non-invasive imaging agent for HSV1-tk gene therapy in hepatoma model using small animal PET. Material and Methods: With the Morris hepatoma MCA cell line and MCA-tk cell line which was transduced with the HSV1-tk gene, in vitro uptake and correlation study between [$^{125}I$]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [$^{124}I$]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. Results:, Specific accumulation of [[$^{125}I$]FIAU was observed in MCA-tk cells but uptake was low in MCA cells. Uptake in MCA-tk cells was 15 times higher than that of MCA cells at 480 min. [$^{125}I$]FIAU uptake was linearly correlated (R2 =0.964, p =0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [$^{125}I$]FIAU was mainly excreted via the renal system in the early phase. Ratios of MCA-tk tumor to blood acting were 10, 41, and 641 at 1 h, 4 h, and 24 h post-injection, respectively. The maximum ratio of MCA-tk to MCA tumor was 192.7 at 24 h. Ratios of MCA-tk tumor to liver were 13.8, 66.8, and 588.3 at 1 h, 4 h, and 24 h, respectively. On small animal PET, [$^{124}I$]FIAU accumulated in substantial higher levels in MCA-tk tumor and liver than MCA tumor. Conclusion: FIAU shows selective accumulation to HSV1-tk expressing hepatoma cell tumors with minimal uptake in normal liver. Therefore, radiolabelled FIAU is expected to be a useful substrate for non-invasive imaging of HSV1-tk gene therapy and therapeutic response monitoring of HCC.

• Radiation Oncology Journal
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• v.19 no.4
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• pp.327-334
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• 2001

Purpose : To find out the role of postoperative adjuvant radiotherapy in the treatment of rectal cancer by comparing survival, pelvic control, complication rate, and any prognostic factor between surgery alone and postoperative radiotherapy group. Materials and methods : From Feb. 1982 to Dec. 1996 total 212 patients were treated by radical surgery with or without postoperative radiotherapy due to rectal carcinoma of modified Astler-Coiler stage $B2\~C3$. Of them, 18 patients had incomplete radiotherapy and so the remaining 194 patients were the database analyzed in this study. One hundred four patients received postoperative radiotherapy and the other 90 patients had surgery only. Radiotherapy was peformed in the range of $39.6\~55.8\;Gy$ (mean: 49.9 Gy) to the whole pelvis and if necessary, tumor bed was boosted by $5.4\~10\;Gy$. Both survival and pelvic control rates were calculated by Kaplan-Meier method and their statistical significance was tested by Log-rank test. Multivariate analysis was peformed by Cox proportional hazards model. Results : 5-year actuarial survival rate (5YSR) and 5-year disease-free survival rate (5YDFSR) of entire patients were $53\%\;and\;49\%$, respectively. 5YSRs of surgery alone group and adjuvant radiotherapy group were $63\%\;vs\;45\%$, respectively (p=0.03). This difference is thought to reflect uneven distribution of stages between two treatment groups (p<0.05 by $\chi^2-test$) with more advanced disease patients in adjuvant radiotherapy group. 5YSRs of surgery alone vs adjuvant radiotherapy group in MAC B2+3, C1, C2+3 were $68\%\;vs\;55\%$ (p=0.09), $100\%\;vs\;100\%$, $40\%\;vs\;33\%$ (p=0.71), respectively. 5YDFSRs of surgery alone vs adjuvant radiotherapy group in above three stages were $65\%\;vs\;49\%$ (p=0.14), $100\%\;vs\;100\%$, $33\%\;vs\;31\%$ (p=0.46), respectively. 5-year pelvic control rate (5YPCR) of entire patients was $72.5\%$. 5YPCRs of surgery alone and adjuvant radiotherapy group were $71\%\;vs\;74\%$, respectively (p=0.41). 5YPCRs of surgery alone vs adjuvant radiotherapy group in B2+3, C1, C2+3 were $79\%\;vs\;75\%$ (p=0.88), $100\%\;vs\;100\%$, $44\%\;vs\;68\%$ (p=0.01), respectively. Multivariate analysis showed that only stage was significant factor affecting overall and disease-free survival in entire patients and also in both treatment groups. In view of pelvic control, stage and operation type were significant in entire patients and only stage in surgery alone group but in adjuvant radiotherapy group, operation type instead of stage was the only significant factor in multivariate analysis as a negative prognostic factor in abdominoperineal resection cases. Conclusion : Our retrospective study showed that postoperative adjuvant radiotherapy could improve the pelvic control in MAC C2+3 group. To improve both pelvic control and survival in all patients with MAC B2 or more, other treatment modality such as concurrent continuous infusion of 5-FU, which is the most standard agent, with radiotherapy should be considered.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.8
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• pp.1121-1127
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• 2015

This study investigated the effects of Myagropsis myagroides ethanol extract (MMEE) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in BALB/c mice. The effects of MMEE on DNCB-induced BALB/c mice were evaluated by examining skin symptom severity, levels of total immunoglobulin E (IgE), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin (IL)-4, and IL-10 in serum, and levels of IL-4, IL-5, IL-13, and $interferon-{\gamma}$ ($IFN-{\gamma}$) in splenocytes. MMEE significantly reduced the total clinical severity score, total IgE levels, as well as $TNF-{\alpha}$ and IL-4 production in an AD mouse model but increased IL-10 production. Production of IL-4, IL-5, and IL-13 in splenocytes was reduced by MMEE, whereas $IFN-{\gamma}$ production increased. These results suggest that MMEE can inhibit the development of AD-like skin lesions in BALB/c mice by modulating the immune response and may be an effective potential therapeutic agent for AD.

• Asia-Pacific Journal of Business Venturing and Entrepreneurship
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• v.7 no.1
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• pp.189-206
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• 2012

It is urgently requested to innovate the management process of business-service areas in all industry such as financial business, services and manufacturing because of recent business trend - de-manufacturing trend and the weight increment of service in all industries. Many enterprises introduce various management - innovation methodologies in order to meet the rapidly changing business environment. Especially in Korea, it is a vogue to introduce the innovation methodology of the advanced company's. According to this style, the six sigma has been introduced over 10 years since late 1990's and it has become a synonym of innovation indeed. But the result of six sigma introduction has not reached to the level of expectation in its beginning. And the "Lean" have been introduced in Korea in the situation of global financial crisis, economic slump and the pursuit of developing country such as China. Many Korea companies pay attention to the "Lean" innovation activity because the TPS(Toyota Production System) is the matrix of Lean and is the motive power of Toyota growth. In this study, it was analyzed for the evolution course, distinctive features and effects of Lean management and was examined for the difference of Lean management between manufacturing industry and business-service areas. From this results, the characteristics of Lean management in business-service was analyzed. After survey of innovation agent in Korea company, the Lean model of business-service Industry was developed and applied. This study will be worthy to show the right direction to the enterprises which are to apply lean methodologies, or the enterprises which examine lean management for competitive advantages or the peoples who research the same topics.

• Journal of Life Science
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• v.26 no.11
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• pp.1289-1297
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• 2016

Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the oral cavity, comprising up to 90% of oral cancer. Oral cancer is characterized by a marked tendency of local invasiveness and is good for early detection and treatment; therefore, it is recognized as a good model for cancer prevention. The present study investigated the antioxidant, thrombin inhibitory, and anti-invasive activities of the solvent fractions of Zingiber officinale Roscoe. Samples were fractionated into hexane, chloroform, ethyl acetate, butanol, and water fractions, and each of these was assayed individually. The water fraction showed the highest extraction yield at 9.79%(w/w). Anti-oxidative activity was analyzed by DPPH assay. Thrombin inhibitory activity was used to analyze thrombin inhibitor assay. Cell viability was detected by the MTS assay. The activity and mRNA expression of MMP-2 and MMP-9 in human oral squamous carcinoma YD-10B cells were examined by zymography and RT-PCR. The antioxidative activities of hexane and water fractions were 92.38% and 92.96%, respectively. In the thrombin inhibitory activity test, water fraction was the highest, with a value of 65.86%. MMP-2/-9 activation was increased in phorbol 12-myristate 13-acetate (PMA)-induced YD-10B cells. MMP-9 activation was increased in thrombin-treated YD-10B cells. In PMA- or thrombin-treated YD-10B cells, the increased mRNA expression and protein activation of MMP-2/-9 were significantly inhibited in the hexane fraction. Therefore, the hexane fraction obtained from a Zingiber officinale Roscoe water extract is a promising therapeutic anti-invasive agent in oral cancer.

• Journal of Life Science
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• v.26 no.11
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• pp.1313-1319
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• 2016

Cancer is a complex disease heterogeneously composed of various types of cells including cancer stem-like cells responsible for relapse and chemoresistance in the tumor microenvironment. The conventional two-dimensional cell culture-based platform has critical limitations for representing the heterogeneity of cancer cells in the three-dimensional tumor niche in vivo. To overcome this insufficiency, three-dimensional cell culture methods in a scaffold-dependent or -free physical environment have been developed. In this study, we improved and simplified the HCT-8 colon cancer cell-based spheroid culture protocol and evaluated the relationship between cancer stemness and responses of chemosensitivity to 5- Fluorouracil (5-FU), a representative anticancer agent against colon cancer. Supplementation with defined growth factors in the medium and the culture dish of the regular surface with low attachment were required for the formation of constant-sized spheroids containing $CD44^+$ and $CD133^+$ colon cancer stem cells. The chemo-sensitivities of $CD44^+$ cancer stem cells in the spheroids were much lower than those of $CD44^-$ non-stem-like cancer cells, indicating that the chemoresistance to 5-FU is due to the stemness of colon cancer cells. Taken together, the inflammation and oncogenic gut environment-sensitive HCT-8 cell-based colon cancer spheroid culture and comparative evaluation using the simplified model would be an efficient and applicable way to estimate colon cancer stemness and pharmaceutical response to anticancer drugs in the realistic tumor niche.

• Korean Journal of Poultry Science
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• v.37 no.3
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• pp.255-263
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• 2010

Inclusion body hepatitis-hydropericardium syndrome (IBH-HPS) is an acute viral disease usually found in broilers aged from 3 to 5 weeks and causes up to 75% mortality. Among the 12 serotypes of fowl adenovirus group 1, serotype-4 (FAdV-4) was identified as a primary agent of IBH-HPS and was usually isolated in IBH-HPS cases in Korea since 2007. To prevent these IBH-HPS outbreaks in Korea, we developed the FAdV-4 inactivated vaccine using Korean isolate (ADL070244) and evaluated the efficacy of this vaccine. For the efficacy test, 2-week-old specific-pathogen-free (SPF) chickens intramuscularly inoculated with 1 or 2 dose of inactivated vaccine were used and challenged with FAdV-4 through either intramuscular or oral route at 2 weeks after vaccination. The vaccine induced good seroconversion which was confirmed by agar gel precipitation (AGP) test. In addition, the vaccine could decrease the FAdV-4 detection rate and histological lesion severity such as lymphocyte infiltration and necrosis in the liver comparing with those of non-vaccination group. Based on the current results, the developed FAdV-4 inactivated vaccine in this study was effective in the terms of reduction of virus detection rate and histological lesions severity. However, it was difficult to confirm the efficacy of the vaccine clearly because of no mortality and clinical signs in the non-vaccinated group after challenge. Therefore, we need further study to develop a standard challenged model system which could clearly evaluate the efficacy of the vaccines for FAdV-4.

• Journal of Chest Surgery
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• v.32 no.5
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• pp.413-421
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• 1999

Background: Ischemia reperfusion injury is known to contribute to the major causes of the early graft failure in lung transplantation. Triiodothyronine (T3) has been suggested to ameliorate ischemia reperfusion injury from both in vivo and in vitro experiments of various organs. Prospecting its beneficial effect for pulmonary allograft preservation, we made a new solution by adding T3 into the extracellular type dextran solution. Material and Method: Twelve adult mongrel dogs underwent left lung allotransplantation. Six donor dogs were flushed with the new solution(Group 1, n=6), and the remaining six were flushed with Euro-Collins solution to serve as controls(Group 2, n=6). Allografts were stored in each preservation solution for 20 hours at 4$^{\circ}C$. Left single lung transplantations were performed. The right pulmonary artery and the right main bronchus were clamped at 15 minutes after the reperfusion and maintained throughout the experiment to evaluate the transplanted left lung function. Result: Arterial carbon dioxide tension was better in group 1 than in group 2 throughout the experiment period and the difference was statistically significant at 2 hours after reperfusion(28.0${\pm}$3.0 mmHg and 53.1${\pm}$17.4 mmHg, p<0.05). The differences of arterial oxygen partial pressure, peak airway pressure and pulmonary vascular resistance showed no statistical significance. The malondialdehyde(MDA) level, measured from tissue obtained at 120 minutes after reperfusion showed no statistically significant difference. The tissue wet/dry ratio of group 1(649${\pm}$27 %) was significantly lower than that of group 2(686${\pm}$71 %, p<0.05). The microscopic examination revealed varying degrees of injury represented mainly by findings such as perivascular neutrophil infiltration, capillary hemorrhage and interstitial congestion. These findings were less severe in group 1 than those in group 2. Conclusion: The new solution demonstrated superior allograft preservation after 20 hour ischemia compared to Euro-Collins solution in canine single left lung transplantation model, these results suggest that T3 might be a promising agent for pulmonary allograft preservation.

• Journal of Preventive Medicine and Public Health
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• v.29 no.3 s.54
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• pp.669-678
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• 1996

Helicobacter pylori is now recognized as causative agent of chronic gastritis and peptic ulcer, and strongly associated with development of gastric carcinoma. With development of sensitive and specific serologic tests to identify individuals infected with Helicobacter pylori, the epidemiologic study of this diseases has been investigated. But it's transmission route is not established, yet. The purpose of this study is to measure the prevalence of Helicobacter pylori infection in healthy children and young adults and to evaluate related factors for Helicobacter pylori infection in Korea. The seroprevalence of Ig G antibodies to Helicobacter pylori was determined using a Enzyme Linked Immunosorbent Assay and we obtained the information, such as demographic characteristics, monthly household income, numbers of family members in the house, numbers of persons using same room, type of house, and type of drinking water through the questionnaire survey. The observed overall seropositivity rate was 25.7%. The rate is increased progressively from 5.8% in the age group $1\sim3$ years to 44.4% in the age group $20\sim29$years($\chi^2$ for trend, p<0.001). Especially, the rate increased steeply from 6.5% in the age group $4\sim6$ years to 20.8% in the age group $7\sim9$ years, and this suggested that elementary school age was the major acquisition time of Helicobacter pylori infection. In multivariate logistic regression model, age, numbers of family members in the house, and type of house was statistically significant variables for Helicobacter pylori infection. Each odds ratio(93% CI) were as follows; base to age group $1\sim9$ years, age group $10\sim19$ years $3.6(2.0\sim6.4)$, age group $20\sim29$ years $7.3(4.1\sim13.1)$ and base to group of $1\sim3$ family members, group of $4\sim5$ family members $2.1(1.1\sim4.0)$, group of 6 or more family members $2.7(1.3\sim5.4)$ and base to apartment, single and multihouse $1.9(1.1\sim3.5)$. Sex, monthly household income, numbers of persons using same room, and type of drinking water was not statistically significant for Helicobacter pylori infection.