• Tuberculosis and Respiratory Diseases
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• v.52 no.1
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• pp.5-13
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• 2002

Background: DNA repair plays a crucial role in protecting the genome from cancer-causing agents. Therefore, a reduced DNA repair capacity can increase the susceptibility to cancer. The human OGG1 (hOGG1) gene encodes DNA glycosylase/apurinic lyase and excise 8-hydroxyguanine, one of the major premutagenic DNA lesions, which is produced by oxygen radical forming agents including smoking. Recently several polymorphisms in the hOGG1 gene were identified, and it is possible that these polymorphism') may affect the DNA repair capacity and thus modulate cancer susceptibility. The relationship between the codon 326 polymorphism (Ser to Cys) in the hOGG1 gene and lung cancer risk was investigated. Materials and Method: The Ser326Cys genotypes were determined using PCR-RFLP analysis in 299 primary lung cancer patients and 186 healthy controls who were frequency (case:control=3:2) matched according to age and sex. Result: The frequencies of the Ser326Cys genotypes (Ser/Ser, Ser/Cys and Cys/Cys) among cases (23.4%, 51.8%, and 24.7%, respectively) were not significantly different from those among the controls (22.6%,52.1% and 25.3%, respectively). When the analyses were stratified according to age, sex, smoking status and packyears of smoking, no significant association between this polymorphism and lung cancer risk was found. Moreover, the Ser326Cys genotype showed no apparent relationship with any of the histological types of lung cancer. Conclusion: These result suggest that the hOGG1 Ser326Cys polymorphism is not a major contributor to individual lung cancer susceptibility in Koreans.

• Tuberculosis and Respiratory Diseases
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• v.58 no.4
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• pp.352-358
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• 2005

Microsatellites are short tandem repeated nucleotide sequences that are present throughout the human genome. Variations in the repeat number or a loss of heterozygosity around the microsatellites have been termed a microsatellite alteration (MA). A MA reflects the genetic instability caused by an impairment in the DNA mismatch repair system and is suggested to be a novel tumorigenic mechanism. A number of studies have reported that MA in the DNA extracted from the plasma occurs at varying frequencies among patients with a non-small cell lung carcinoma (NSCLC). The genomic DNA from 9 subjects with a non-small cell lung cancer (squamous cell cancer 6, adenocarcinoma 2, non-small cell lung cancer1) and 9 age matched non-cancer control subjects (AMC: tuberculosis 3, other inflammatory lung disease 6) and 12 normal control subjects (NC) were extracted from the peripheral blood leukocytes and plasma. Three microsatellite loci were amplified with the primers targeting the Gene Bank sequence D21S1245, D3S1300, and D3S1234. MA in the form of an allelic loss or a band shift was examined with 6% polyacrylamide gel electrophoresis and silver staining. None (0/12) of the NC subjects less than 40 years of age showed a MA in any of the three markers, while 88.9%(8/9) of the AMC above 40 showed a MA in at least one of the three markers (p<0.05). Sixty percent(6/10) of the control subjects with a smoking history showed a MA in one of the three markers, while 9.1%(1/11) of the control subjects without smoking history showed a MA (p<0.05). However, not only did 66.7%(6/9) of lung cancer patients show a MA in at least one of the three markers but so did 88.9%(8/21) of the AMC patients (p>0.05). In conclusion, a MA in the D21S1245, D3S1300, and D3S1234 loci using DNA extracted from the plasma was detected in 66.7% of lung cancer while no MA was found in the young non-smoking control subjects. However, many of the non-cancer control subjects (aged smokers) also showed a MA, which compromised the specificity of the MA analysis as a screening test. Therefore, a further study with a larger sample size will be needed.

• Tuberculosis and Respiratory Diseases
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• v.63 no.1
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• pp.42-51
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• 2007

Background: TRAIL is a cytokine that selectively induces apoptosis in various cancer cell lines. Gefitinib is new targeted drug applied in lung cancer that selectively inhibits EGFR tyrosine kinase. However, lung cancers have shown an initial or acquired resistance to these drugs. This study examined the effect of IGF-1R and its blockade on enhancing the sensitivity of lung cancer cell lines to TRAIL and gefitinib. Methods: Two lung cancer cell lines were used in this study. NCI H460 is very sensitive to TRAIL and gefitinib. On the other hand, A549 shows moderate resistance to TRAIL and gefitinib. The IGF-1R blockade was performed using adenoviruses expressing the dominant negative IGF-1R and shRNA to IGF-1R and AG1024 (IGF-1R tyrosine kinase inhibitor). Results: The adenovirus expressing dominant negative IGF-1R(950st) induced the increased expression of defective IGF-1R on the lung cancer cell surface, and the adenovirus-shIGF-1R effectively decreased the level of IGF-1R expression on cell surface. The genetic blockade of IGF-1R by the adenovirus-dnIGF-1R and AG1024 increased the sensitivity of A549 cells to TRAIL. The reduction of IGF-1R by transduction with ad-shIGF-1R also increased the sensitivity of the A549 cells to gefitinib. Conclusion: The blockade of IGF-1R through various mechanisms increased the sensitivity of the lung cancer cell line that was resistant to TRAIL and gefitinib. However, further studies using other cell lines showing acquired resistance as well as in vivo animal experiments will be needed.

• Tuberculosis and Respiratory Diseases
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• v.60 no.6
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• pp.638-644
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• 2006

Backgrounds: This study investigated whether or not a polymorphism in the gene encoding the surfactant protein A(SP-A) has any bearing on the individual susceptibility to the development of chronic obstructive pulmonary disease(COPD) in a genetically homogenous Korean population. Methods: The genotypes of 19 COPD patients and 20 healthy neonates as controls were tested using a polymerase chain reaction followed by restriction fragment length polymorphism analysis for the SP-A gene. Results: The specific frequencies of the 6A2 and 6A18 alleles of SP-A1 and the 1A2 allele of SP-A2 were much higher in the COPD group than control group (p<0.05). However, the frequencies of the 6A3 and 6A4 alleles of SP-A1 and the 1A0 allele of SP-A2 in the COPD group were significantly lower than the control group. In the COPD group, the frequencies of the +50 locus genotypes GG of SP-A1 and the +9 locus genotypes CC of SP-A2 were 85.0% and 60.6%, respectively, and 19.7% and 24.8% in the control group, respectively. The frequencies of the polymorphic genotypes or alleles showed a statistically significant difference between the COPD group and the control group (P<0.05). Conclusion: A genetic polymorphism in SP-A is associated with the development of COPD in the Korean population.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.79-92
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• 2007

Oxidative stress have known to be a risk factor for the degenerative processes and closely related to a lot of diseases. It is well established that antioxidants are good in protection and therapeutic means against oxidative damage. There is increasing interest in natural antioxidants and many natural antioxidants have been found and utilized as the possible protection for various diseases and skin aging. We have screened natural antioxidant agents for cosmeceuticals, nutraceuticals, and drugs as therapeutic and preventive means against oxidative stress, and have developed a number of novel antioxidants from various natural sources. A novel melanin synthesis inhibitor, Melanocin A, isolated from the metabolite of a fungal strain Eupenicillium shearii F80695 inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with $IC_{50}$ value of 9.0 nM and MIC value of $0.9\;{\mu}M$, respectively. Melanocin A also exhibited potent antioxidant activity by scavenging of DPPH and superoxide anion radicals. UV was found to increase the level of hydrogen peroxides and other reactive oxygen species (ROS) in skin tissues. This increase in ROS may not only alter the structure and function of many genes and proteins directly but may also modulate their expressions through signal transduction pathways and, ultimately, lead to skin damage. We investigated the effect of Melanocin A on UV-induced premature skin aging. Firstly, the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9 expression in an immortalized human keratinocyte cell line, HaCaT in vitro was investigated. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and Melanocin A suppressed this expression in a dose-dependent manner. We then investigated UV-induced skin changes in hairless mice in vivo by Melanocin A. Chronic exposure of hairless mouse dorsal skin to UV increased skin thickness and induced wrinkle formation and the gelatinase activities of MMP-2 and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic skin changes and MMP-2 and MMP-9 expression. These results show that Melanocin A can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that Melanocin A should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging. Terrein is a bioactive fungal metabolite isolated from Penicillium species. Terrein has a relatively simple structure and can be easily synthesized. However, the biologic effects of terrein are comparatively unknown. We found for the first time that terrein potently inhibit melanin production in melanocytes and has a strong hypopigmentary effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment of Mel-Ab cells with terrein (10-100 mM) for 4 days significantly reduced melanin levels in a dose-dependent manner. In addition, terrein at the same concentration also reduced tyrosinase activity. We then investigated whether terrein influences the extracellular signal-regulated protein kinase (ERK) pathway and the expression of microphthalmia-associated transcription factor (MITF), which is required for tyrosinase expression. Terrein was found to induce sustained ERK activation and MITF down-regulation, and luciferase assays showed that terrein inhibits MITF promoter activity in a dose-dependent manner. To elucidate the correlation between ERK pathway activation and a decreased MITF transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was applied before terrain treatment and found to abrogate the terrein-induced MITF attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h. These results suggest that terrain reduces melanin synthesis by reducing tyrosinase production via ERK activation, and that this is followed by MITF down-regulation.

• Food Science of Animal Resources
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• v.27 no.4
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• pp.531-537
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• 2007

Small amounts of trans fatty acids exist naturally in beef and dairy foods. Also, they can be produced in the process of partial hydrogenation to manufacture shortning or margarine. They can provide a better palatability and shelf life. According to the recently studies, trans fatty acids can raise health risk such as heart diseases and coronary artery diseases. They can also increase low-density lipoprotein (LDL) cholesterol and decrease high-density lipoprotein (HDL) cholesterol in the blood plasma, therefore increasing the risk of atherosclerosis and diabetes. The aim of this study was to determine total lipids and trans fatty acids (TFAs) content in processed foods and meat products. The analysis of trans fatty acids was performed in 28 samples of donuts, 18 samples of bakeries, 4 samples of frozen doughs, 2 samples of popcorns, and 4 samples of meat products (ham, sausage, nuget, and bacon). Total lipids in processed foods and meat products were extracted by chloroform-Methanol method and acid digestion, respectively. They were analyzed by gas chromatography using a SP-2560 column and flame ionization detector. The amounts of TFAs per 100 g of foods were 0-3.3% (0.74% on average) in donuts, 0.2-5.8% (1.18% on average) in bakeries, 0.2-6.3% (1.93% on average) in frozen doughs, and 0-5.8% in popcorns. Meat products such as ham, sausage, and nuget analyzed 0.1% of TFAs, respectively and trans fatty acids in bacon were not detected. As a result, the distribution of TFAs in processed foods was widely ranged from O% to 6.3% according to manufacturers and types of products, whereas the content of TFAs in meat products ranged from 0% to 0.1%.

• Journal of Life Science
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• v.29 no.1
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• pp.112-117
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• 2019

Herbal medicines are widely used as therapeutic products in many countries. Corni fructus (CF), the dried ripe sarcocarp of Cornus officinalis Sieb. et Zucc (Cornaceae), has been used for thousands of years in traditional medicine and has been reported to be effective for the prevention and treatment of various diseases, such as kidney diseases and diabetes. Recent research on CF has documented a wide spectrum of therapeutic properties, which include anti-inflammatory, ant-oxidative, immunomodulatory, and anti-cancer effects. However, there is no information on its safety. Therefore, in this study, the toxicity of water extract of CF to ICR mice was investigated. The mice received a single dose of water extract of CF (1,000, 2,000, and 5,000 mg/kg of body weight) via the oral route. Mortality, clinical signs, body weight changes, gross findings, and weights of the principal organs after 14 d were then assessed. The results revealed no adverse effects of CF as determined by clinical signs, body weights, or organ weights and no gross pathological findings in any of the treatment groups. These results suggest that the 50% lethal dose and approximated lethal dose of CF extract is over 5,000 mg/kg. The findings provide scientific evidence for the safety of CFs.

• The Korean Society of Law and Medicine
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• v.21 no.2
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• pp.209-244
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• 2020

TMS and tDCS are non-invasive devices that treat the diseases of patients or individual users, and manage or improve their health by applying stimulation to a brain through magnetism and electricity. The effect and safety of these devices have proved to be valid in several diseases, but research in this area is still much going on. Despite increasing cases of their application, legislations directly regulating TMS and tDCS are hard to find. Legal regulation regarding TMS and tDCS in the United States, Germany and Japan reveals that while TMS has been approved as a medical device with a moderate risk, tDCS has not yet earned approval as a medical device. However, the recent FDA guidance, European MDR changes, recalls in the US, and relevant legal provisions of Germany and Japan, as well as recommendations from expert groups all show signs of tDCS growing closer to getting approved as a medical device. Of course, safety and efficacy of tDCS can still be regulated as a general product instead of as a medical device. Considering multiple potential impacts on a human brain, however, the need for independent regulation is urgent. South Korea also lacks legal provisions explicitly regulating TMS and tDCS, but they fall into the category of the grade 3 medical devices according to the notifications of the Korean Ministry of Food and Drug Safety. And safety and efficacy of TMS are to be evaluated in compliance with the US FDA guidance. But no specific guidelines exist for tDCS yet. Given that tDCS devices are used in some hospitals in reality, and also at home by individual buyers, such a regulatory gap must quickly be addressed. In a longer term, legal system needs to be in place capable of independently regulating non-invasive brain stimulating devices.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.50 no.3
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• pp.271-278
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• 2024

The human skin is an organ that protects the body from physical and chemical factors. The skin is the largest and most massive of the body's organs and is composed of the epidermis, dermis, and subcutaneous tissue. Constant UV exposure to the skin can cause DNA damage, oxidation of proteins, and contribute to adult diseases. Nypa fruticans Wurmb (NF), rich in phytochemicals (polyphenols and flavonoids), has been traditionally used for treating respiratory and other diseases. This study investigated the effects of NF ethyl acetate fraction (ENF) on DNA damage healing and inhibition of wrinkle-related factors in UVB-stimulated Hs68 cells. Westernblotting was used to assess the expression of DNA damage-related proteins and wrinkle-related protein factors. In addition, the wound recovery capability of ENF was confirmed through wound-healing experiments. ENF significantly suppressed the expression of DNA damage-related proteins Phosphorylated H2AX (γ-H2AX), checkpoint kinase 2 (Chk2), protein53 (p53), and Phosphorylated protein53 (p-p53). Furthermore, ENF inhibited the expression of wrinkle-related proteins matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-9 (MMP-9). High concentrations of ENF also enhanced wound healing in Hs68 cells. ENF is thought to have the potential to heal DNA damage by significantly suppressing the expression of γ-H2AX, Chk2, p53, and p-p53, as well as to inhibit wrinkle formation by suppressing the expression of MMP-1, MMP-3, and MMP-9. These results suggest that ENF can be used as a natural resource to suppress skin damage caused by UVB by regulating the γ-H2AX, Chk2, p53, and MMP pathways in Hs68 cells induced by UVB.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.135-143
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• 2009

There is currently increased interest in the identification of antioxidant compounds that are pharmacologically potent and have low or no side effects. Plants produce significant amounts of antioxidants to prevent the oxidative stress caused by photons and oxygen, therefore they represent a potential source of new compounds with antioxidant activity. Moutan Root Sark (MRS) has been frequently used as analgesic. antispasmodic, anti-inflammatory and remedies for female diseases. In this study. the antioxidant activity of extract from MRS was studied in vitro methods by measuring the antioxidant activity by TEAC, measuring the scavenging effects on reactive oxygen species (ROS) [superoxide anion, hydroxyl radical] and on reactive nitrogen species (RNS) [nitric oxide and peroxynitrite] as well as measuring the inhibitory effect on $Cu^{2+}$ induced human LDL oxidation and the inhibitory effect on collagen induced platelet aggregation. The MRS extracts were found to have a potent scavenging activity, as well as an inhibitory effect on LDL oxidation and on platelet aggregation. In conclusion, the MRS extracts have anti-oxidative and anti-atherosclerotic effects in vitro system, which can be used for developing pharmaceutical drug against oxidative stress and atherosclerosis.