• Archives of Pharmacal Research
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• v.29 no.10
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• pp.911-920
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• 2006

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

• Journal of Nutrition and Health
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• v.52 no.1
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• pp.17-25
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• 2019

Purpose: Obesity is a major health problem of global significance because it is clearly associated with an increased risk of health problems, such as nonalcoholic fatty liver disease (NAFLD), diabetes, cardiovascular diseases, and cancer. Lonicera caerulea (LC) originates from high mountains or wet areas and has been used as a traditional medicine in northern Russia, China, and Japan. LC contains a range of bioactive constituents, such as vitamins, minerals, and polyphenols. This study examined the anti-obesity effects of LC during differentiation in preadipocytes. Methods: The cell viability assay was performed after the differentiation of 3T3-L1 cells for 7 days. Oil Red O staining was used to visualize the changes in lipid droplets in 3T3-L1 cells and mouse adipose-derived stem cells (MADSCs). The mRNA expression of obesity-related genes was determined by quantitative real-time PCR. Results: According to the results of Oil Red O staining, the lipid levels and size of lipid droplets in the adipocytes were reduced and the LC extract (LCE, 0.25-1 mg/mL) markedly inhibited adipogenesis in a dose-dependent manner. The treatment of LCE also decreased the mRNA expression of peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), CCAAT/enhancer binding protein-${\alpha}$ ($C/EBP{\alpha}$), and sterol regulatory element binding protein 1 (SREBP1) in 3T3-L1 cells. Western blot analysis showed that the $PPAR{\gamma}$, $C/EBP{\alpha}$, and SREBP1 protein levels in both 3T3-L1 and MADSC were reduced in a dose-dependent manner. Conclusion: These results suggest that LCE can inhibit adipogenic differentiation through the regulation of adipogenesis-related markers.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.521-531
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• 2023

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (E_max) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

• Korean Chemical Engineering Research
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• v.62 no.3
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• pp.274-280
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• 2024

Machine learning techniques utilizing neural networks have been employed in various fields such as disease gene discovery and diagnosis, drug development, and prediction of drug-induced liver injury. Disease features can be investigated by molecular information of DNA. In this study, we developed a neural network to predict the length of DNA and the number of DNA species in mixture solution which are representative molecular information of DNA. In order to address the time-consuming limitations of gel electrophoresis as conventional analysis, we analyzed the dynamic data of a microfluidic concentrating device. The dynamic data were reconstructed into a spatiotemporal map, which reduced the computational cost required for training and prediction. We employed a convolutional neural network to enhance the accuracy to analyze the spatiotemporal map. As a result, we successfully performed single DNA length prediction as single-variable regression, simultaneous prediction of multiple DNA lengths as multivariable regression, and prediction of the number of DNA species in mixture as binary classification. Additionally, based on the composition of training data, we proposed a solution to resolve the problem of prediction bias. By utilizing this study, it would be effectively performed that medical diagnosis using optical measurement such as liquid biopsy of cell-free DNA, cancer diagnosis, etc.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.433-440
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• 1998

Purpose : Although small ceil lung cancer (SCLC) has high response rate to chemotherapy and radiotherapy (RT), the prognosis is dismal. The authors evaluated survival and failure patterns according to the prognostic factors in SCLC patients who had thoracic radiation therapy with chemotherapy. Materials and Methods : One hundred and twenty nine patients with SCLC had received thoracic radiation therapy from August 1985 to December 1990. Seventy-seven accessible patients were evaluated retrospectively among 87 patients who completed RT. Median follow-up period was 14 months (2-87months). Results : The two years survival rate was 13$\%$ with a median survival time of 14 months. The two year survival rates of limited disease and extensive disease were 20$\%$ and 8$\%$, respectively, with median survival time of 14 months and 9 months, respectively. Twenty two patients (88$\%$) of limited disease showed complete response (CR) and 3 patients (12$\%$) did partial response (PR). The two year survival rates on CR and PR groups were 24$\%$ and 0$\%$, with median survival times of 14 months and 5 months. respectively (p=0.005). No patients with serum sodium were lower than 135 mmol/L survived 2years and their median survival time was 7 months (p=0.002). Patients whose alkaline phophatase lower than 130 IU/L showed 26$\%$ of 2 year survival rate and showed median survival time of 14 months and those with alkaline phosphatase higher than 130 IU/L showed no 2 year survival and median survival time of 5 the months, respectively (p=0.019). No statistical differences were found according to the age, sex, and performance status. Among the patients with extensive disease, two rear survivals according to the metastatic sites were 14$\%$, 0$\%$, and 7$\%$ in brain, liver, and other metastatic sites, respectively, with median survival time of 9 months, 9 months, and 8 months, respectively (p>0.05). Two year survivals on CR group and PR group were 15$\%$ and 4$\%$, respectively, with a median survival time of 11 months and 7 months, respectively (p=0.01). Conclusion : For SCLC, complete response after chemoradiotherapy was the most significant prognostic tactor. To achieve this goal. there should be further investigation about hyperfractionation, dose escalation, and compatible chemo-radiation schedule such as concurrent chemo-radiation and early radiation therapy with chemotherapy.

• Journal of Chest Surgery
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• v.36 no.6
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• pp.397-403
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• 2003

Background: The research sought to identify the clinical features of pleomorphic carcinoma of the lung generally known as a rare subtype in accordance with the lung cancer classification done in 1999 by WHO. Material and Method: 250 cases of surgically resected lung cancers were collected in this hospital from January 1992 to December 2001. This study included 42 cases of pleomorphic carcinoma diagnosed through light microscope and immunohistochemistry. Result: Out of 42 cases, males represented 31, and females 11, the age ranged from 26 to 77. Main clinical symptoms included coughing, hemoptysis, sputum. Diagnoses disclosed the stage as stage la in 3 cases (7%), Ib in 16 (38%), IIa in 1 (2%), IIb in 8 (19%), IIIa in 15 (35%), and IIIb in 1 (2%). Out of these, no lymph node metastasis was represented in 23 cases (54%), while N1 and N2 involving lymph node metastasis was shown 19 cases (46%). A total of 19 patients developed metastasis, comprising the brain in 5 cases (26%), bone in 4 (21%), muscle in 4 (21%), Lymph node in 2 (10%), and 1 liver, ovary, contralateral lung, and adrenal gland, respectively. The size of the tumor ranged from 1 cm to 11 cm, averaging 5.85 cm. Out of the 42 patients, the total two-year and five-year survival rates in accordance with the Kaplan-Meier method represented 26% and 13%, respectively, These figures compared to the corresponding 44% and 34% in cases other than pleomorphic carcinoma from the survey target of 256 cases, proved to be significantly low (p<0.002). No significant difference was found in the survival rates compared between age and tumor size, between stage I and above stage II, and between N0 and above N1. Patients who developed postoperative metastasis all died, and showed significantly low survival rates (p<0.002) compared to those patients without metastasis. Conclusion: With the new diagnosis method of f999 WHO's lung cancer classification applied, pleomorphic carcinoma showed a higher prevalence rate than under previous classifications, their postoperative survival rate was significantly low compared to histologic type of non small cell lung carcinomas.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.9
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• pp.1243-1252
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• 2009

We investigated a method to improve anticancer activities of Acer mono by ultra high pressure extraction process. The extract yields by ultra high pressure were 9.49% and 9.87% for 5 min and 15 min processing time, respectively, which were relatively higher than 3$\sim$4% of conventional extraction processes due to their resid bark structure. The extract for 15 minutes extraction (HPE15) showed higher potent scavenging effect as 94.56% than the control, BHA as 93.24%. On SOD-like test, HPE15 also showed the highest activity as 38.6% at 1.0 mg/mL concentration. The cytotoxicity of HPE15 on normal human lung and kidney cell were below 23.54% in adding 1.0 mg/mL. Generally, human cancer cell growth stomach adenocarcinoma (AGS), lung adenocarcinoma (A549), breast adenocarcinoma (MCF-7), colon adenocarcinoma (Caco-2) and liver adenocarcinoma (Hep3B) were inhibited up to 75% with higher selectivity of above 4.0. High antioxidant activity of HPE15 resulted in high anticancer activity, and its activity was also due to higher yields of Acer mono by ultra high pressure extraction process. It was also proved by HPLC comparison analysis.

• Korean Journal of Medicinal Crop Science
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• v.10 no.2
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• pp.132-138
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• 2002

This study was performed to determine the antimutagenic and cytotoxic effect of ,Kalopanacis cortex endothelium. Methanol extract was used on Salmonella typhimurium TA98, TA100 and three cancer cell lines. In the Ames test, methanol extract of Kalopanacis cortex endothelium alone did not exhibit any mutagenicity but showed substantial inhibitory effects against mutation induced by 4-nitroquinoline-l-oxide(4NQO), N'-methyl- N'-nitro-N-nitrosoguanidine(MNNG) and benzo(a)pyrene(B(a)P). The methanol extract of Kalopanacis cortex endothelium showed approximately 79.29% and 75.38% inhibitory effect on the mutagenesis induced by 4NQO and B(a)P, respectively, against TA98 strain. Whereas 79.49%, 89.3% and 68.85% inhibitions were observed on the mutagenesis induced by 4NQO, MNNG and B(a)P against TA100 strain. Methanol extracts from Kalopanacis cortex endothelium showed high antimutagenic effects against 4NQO, MNNG and B(a)P. The anticancer effects of methanol extract from Kalopanacis cortex endothelium against human lung carcinoma(A549), human breast adenocarcinoma (MCF-7) and human hepatocellular carcinoma(Hep3B) were investigated. The treatment of 0.5mg/ml Kalopanacis cortex endothelium methanol extracts had the highest cytotoxicity against A549(81.54%), followed by MCF-7(81.92%) and Hep3B (78.57%). In contrast 0.5mg/ml treatment of methanol extracts from Kalopanacis cortex endothelium had only $4{\sim}25%$ cytotoxicity on normal human liver cell(293).

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.4 no.2
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• pp.207-212
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• 2001

Purpose: Mycoplasma pneumoniae infection is relatively common in childhood. Its extrapulmonary manifestations have been reported so much, but hepatitis associated with it has not been studied yet until now in Korea. Methods: We performed the prospective study of 19 cases that had AST and ALT>50 IU/L respectively without evidence of hepatitis A, B, C, cytomegalovirus, and Ebstein-Barr virus infections amongst 143 patients with M. pneumoniae pneumonia who were admitted to the Department of Pediatrics, Seoul Red Cross Hospital from Jan. 1999 to Dec. 2000. Results: 1) Hepatitis occurred in 13.3% of Mycoplasma pneumoniae infection, especially in fall and winter times. The average age was 4.86 years and male to female ratio was 2.2:1. 2) Vomiting was developed in 21.1%, diarrhea in 36.8%, and hepatomegaly in 21.1%, respectively. And leukocytosis was noted in 21.1%, eosinophilia in 15.4%, anemia in 10.5%, and thrombocytosis in 5.3%, respectively. The average level of C-reactive protein was $6.34{\pm}4.82$ mg/dl. 3) There was no hyperbilirubinemia, but hypoalbuminemia was detected in 42.1%. The average serum levels of AST and ALT were $214.05{\pm}183.22$ IU/L and $284.16{\pm}286.84$ IU/L, respectively. 4) Chest radiology showed lobar or lobular consolidation in 73.7%, bronchial infiltration in 26.3%, and pleural effusion in 31.6%. 5) The average length of hospitalization was 7.9 days, and the average length of normalization of serum transaminases was 8.8 days. All patients recovered within 2 weeks completely. Conclusion: The prognosis of M. pneumoniae hepatitis is good. However, its incidence is not so low that liver function should be considerately checked in case of M. pneumoniae infection.

• Journal of Life Science
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• v.24 no.10
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• pp.1151-1156
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• 2014

Traditional medicinal plants are widely used to treat many diseases, such as inflammation, infections, and even cancer. Ulmus macrocarpa Hance, a Chinese elm species, is distributed in Korea, China, and Japan. The stem bark is widely employed in Korean traditional medicine to treat dermatitis, mastitis, and edema. The aim of this study was to investigate whether water extract of U. macrocarpa Hance bark (Ulmus cortex) has a immune-modulating function in a mouse model. Three different concentrations (30 mg/kg, 100 mg/kg, and 300 mg/kg) of Ulmus cortex water extract (UCWE) were orally administered to mice for 14 days, and their immune responses were analyzed. Cytokines, such as interleukin (IL)-2, IL-12, and IFN-${\gamma}$, increased in the blood of UCWE-fed groups when compared with a control group. In contrast, the IL-4 level did not change in any of the UCWE-fed groups Cell-mediated cytotoxicity was also assayed using lymphokine-activated killer cells (LAK). LAK showed greater cytotoxicity in the UCWE-fed groups than LAK in the control group. Internal organ indices, such as liver, kidney, spleen, and thymus, were similar in all the groups, including the control group, indicating that UCWE may have been nontoxic in the experimental animals. These data suggest that UCWE has an immune-modulating function in a mouse model.