Effects of Nattokinase fibrinol (NKF), defined as a fibrinolytic product, on fibrinolytic and atherogenetic markers were studied for healthy adults (20-31 years old), who is smoking more than 20 cigarettes per day. Subjects were divided into 29 for NKF group and 10 for placebo group in a short term study. They were given 2 tablets of NKF (4,000 unit) or placebo tablet and thereafter blood samples were collected at 0, 2, 4 hr prerid. For a 4-week long term study, 15 subjects for NFK group and 10 subjects for placebo group were supplemented one tablet of each NKF (2,000 unit) and placebo per day, respectively. Blood samples were collected at 0, 1, 2, 4 weeks later. The short-term experimental trial showed that NKF remarkably increased fibrinolytic activity at 2hr after consumption, which was maintained up to 4 hr, relative to that of placebo, while NKF reduced the euglobulin clot lysis time (ECLT) and retarded the activated partial thromboplastin time (aPTT), as compared to placebo group. NKF supplementation for 4 weeks elevated fibrinolytic activity, shortened ECLT and retarded aPTT. Furthermore, NKF supplementation increased anti-atherogenic index by decreasing triglyceride (TG) and elevating high-density lipiprotein (HDL)-cholesterol. These results indicate that NKF supplementation for short term or long term might have beneficial effects on preventing and treating cardiovascular disease by increasing fibrinolytic activity and improving atherogenic markers such as hyperlipidemia.
We tried to analyze the HPV prevalence and HPV genotypes of sexually high-risk women living in Busan, the biggest seaport of South Korea. Six hundred sixty women engaging in high-risk occupations participated in this study. The prevalence of HPV infection and HPV genotyping were determined with $MyGene^{(R)}$ HPVDNA chip, which consisted of 16 high-risk HPV genotypes (oncogenic genotypes) and 8 low-risk HPV genotypes. The overall prevalence of HPV infection in this study population was 39.1% (258/660) and the 20's showed the highest prevalence of HPV infection (51.5%). The dominant HPV genotypes including single or multiple HPV-infected women were resulted in HPV-16 (15.9%), -53 (10.2%), -58 (7.7%), -18 (5.2%) in case of high-risk HPV genotype and HPV-70 (10.4%), -6 (4.1%), -11 (2.0%) in case of low-risk HPV genotypes. Remarkably, the proportion of women infected with high-risk HPV genotypes (62.0%) was almost four times higher than those of women infected with low-risk HPV genotypes (14.7%) and high/low-risk HPV genotypes (12.0%). Among the 258 HPV-infected women, single infection was 175, double infection 66, triple infection 12, quadruple infection 4, quintuple infection 1, respectively. Our finding suggests that the introduction and development of effective HPV vaccines should consider the current status of HPV genotypic infection in South Korean women.
This study analyzed whether human chorionic gonadotropin (hCG) induces ER stress via the IRE/XBP1 pathway in mouse Leydig tumor (mLTC-1) cells. In a previous study, we demonstrated that the unfolding protein response (UPR) plays an important role in the expression of steroidogenic enzymes by modulating the ATF6 pathway, as well as ER stress-mediated apoptosis in hCG-stimulated Leydig cells. Although UPR signaling has been reported to regulate the IRE1/XBP1 pathway, it is not known whether hCG-induced ER stress in Leydig cells can activate the pathway. To investigate the activation of the IRE1/XBP1 pathway in mLTC-1 cells after hCG treatment, we performed a Western blot analysis to detect the phospho-IRE1 protein and an RT-PCR analysis to validate splicing of XBP1 mRNA. We used ER stress-activated indicator (ERAI) constructs for monitoring the activity of IRE1 and then analyzed by fluorescence microscopy and flow cytometry. The expression levels of the phospho-IRE1 protein markedly increased in response to the hCG treatment. In the mLTC-1 cells transfected with an F-XBP1-venus/F-$XBP1{\Delta}DBD$-venus construct, the hCG treatment led to the appearance of green fluorescent cells and detectable fluorescence in the nucleus and cytosol, respectively. In addition, splicing of XBP1 mRNA significantly increased after the hCG treatment. Taken together, these results indicate that hCG-induced ER stress leads to activation of the IRE1/XBP pathway in Leydig cells.
Choi, Hye Jin;Han, Young Sun;Park, Doo Hyun;Oh, Bo Young;Hur, Myung Je;Jo, Nam-Gyu;Kim, Young Hee;Kim, Jong-Guk
Journal of Life Science
/
v.24
no.10
/
pp.1110-1117
/
2014
Tidal flats are continuously contaminated by human activities. This study assessed the bioremediation efficiency of tidal flat soil using microcosm reactors and microorganisms originating from the tidal area. We screened 135 bacterial strains that produce extracellular enzymes from the tidal area located in the North port of Incheon bay. Two bacterial strains (Pseudoalteromonas sp. and IC35 Halothiobacillus neapolitanus IC_S22) were selected and used in the microcosm reactors, which were specially designed to functionally mimic the ecological conditions of the tidal flats. Pseudoalteromonas sp. IC35 was selected based on its relatively high activity of the enzymes amylase, cellulose, lipase, and protease. Halothiobacillus neapolitanus IC_S22 was selected for oxidation of sulfur. The M1 and M2 microcosm reactors were operated by continuous feeding of seawater under the same conditions, but M2 was first inoculated with Pseudoalteromonas sp. IC35 before the seawater feeding. The initial COD in both the M1 and M2 microcosm reactors was 320 mg/l. The final COD was 21 mg/l (M1) and 7 mg/l (M2). The M3 and M4 microcosm reactors were operated by continuous feeding of seawater under the same conditions, but M4 was first inoculated with H. neapolitanus IC_S22. The initial sulfate concentration in both the M3 and M4 microcosm reactors was 660 mg/l, and the maximum sulfate concentration was 1,360 mg/l (M3) and 1,600 mg/l (M4).
Chungkookjang has several functional properties, such as fibrinolytic activity, anticancer effects, and antioxidant effects. However, children do not like Chungkookjang because of its foul odor. A mixed culture of Bacillus subtilis MC31 and Lactobacillus sakei 383 was used to improve the production of GABA in Chungkookjang and its flavor. Most of the foul odor of Chungkookjang was removed. The slime content and viscosity of Chungkookjang fermented in the mixed culture were similar to those of commercial Chungkookjang when B. subtilis MC31 and Lactobacillus sakei 383 were inoculated in a 1:1 ratio. The maximum GABA content was obtained when Chungkookjang was fermented with B. subtilis MC31 and L. sakei 383, which was fermented at $37^{\circ}C$ for 72 hr. During the period of fermentation, the viable cell number of B. subtilis MC31 reached a peak (log 9.13 CFU/g) at six days, and L. sakei 383 reached a peak (log 6.78 CFU/g) at two days. The moisture, crude ash, crude protein, crude fat, and crude fiber contents were 61.71%, 2.05%, 17.54%, 8.36%, and 1.95%, respectively. The amino-type nitrogen content of Chungkookjang fermented by B. subtilis MC31 and L. sakei 383 was less than Chungkookjang fermented by B. subtilis MC31 alone. The ammonia-type nitrogen and reducing sugar content of the Chungkookjang fermented by B. subtilis MC31 and L. sakei 383 were higher than that of steamed soybean. The glutamic acid and GABA content detected with an amino acid analyzer were 1.40 mg/g and 0.47 mg/g, respectively. These results suggest that fermentation with B. subtilis MC31 and L. sakei 383 in a 1:1 ratio removes more of the foul odor and increases the GABA content compared with single fermentation.
Hwang, In Sik;Koh, Eun Kyoung;Kim, Ji Eun;Lee, Young Ju;Kwak, Moon Hwa;Go, Jun;Sung, Ji Eun;Song, Sung Hwa;Hwang, Dae Youn
Journal of Life Science
/
v.24
no.5
/
pp.467-475
/
2014
Sea buckthorn (Hippophae rhamnoides L.) is a well-known and rich source of biologically active compounds, such as flavonoids, carotenoids, steroids, vitamins, tannins, and oleic acid. The effects of sea buckthorn fruit extract (SBFE) on ultraviolet (UV)-induced cell death was investigated in SK-MEL-2 cells cotreated with UV and a low concentration (LoC), medium concentration (MeC), or high concentration (HiC) of SBFE. Cell viability gradually decreased in accordance with an increase in the UV dose. The cell viability of the UV+SBFE cotreated cells increased significantly compared to that of UV+vehicle-treated cells during the application of an appropriate UV radiation dose (400 mJ). In addition, the number of 4',6-diamidino-2-phenylindole (DAPI), propidium iodine (PI)-, and annexin V-stained apoptotic cells was higher in the UV+vehicle-treated cells than in the UV untreated cells. The decrease of apoptotic cell numbers varied in each treated group, but it was most significant in the SBFE-treated group. The number of PI-stained cells dramatically decreased in accordance with the concentration of SBFE, and the maximum decrease was detected in the UV+HiC-treated group. In addition, Bax expression increased and Bcl-2 expression decreased in the SBFE-treated group compared with the UV-only treated group. The level of caspase-3 remained constant in all the groups. These results suggest that SBFE may contribute to a recovery from UV-induced cell death through the regulation of apoptotic protein expression and that it may have potential therapeutic utility in ameliorating UV-induced skin ageing.
Kang, Shin Ae;Chun, Sung Sik;Kang, Shin Kwon;Chung, Young Chul;Cheon, Eun Woo;Cho, Sang Uk;Jung, Kyung Hwa;Ahn, Soon Cheol;Yu, Hak Sun
Journal of Life Science
/
v.24
no.5
/
pp.567-572
/
2014
Extracts of Platycodon grandiflorum have been reported to show anti-inflammatory, antioxidant, anti-metastatic, and hepato-protective effects. This study was designed to evaluate T-cell activation and M1/M2 differential macrophage activation by extracts of P. grandiflorum or P. grandiflorum containing various medicinal herbs. Using real-time RT-PCR, we analyzed expression levels of c-fos, and CD40L (T-cell activation markers) in splenocytes and iNOS, Ym1, and ARG1 in RAW 246.7 cells after treatment of CC (hot water extract of P. grandiflorum), MAEK (hot water extract of P. grandiflorum [82%] and six different plants), and HWAL (hot water extract of P. grandiflorum [7%] and eight different plants. The results showed that MAEK significantly elevated the expression of T-cell activation markers of splenocytes, with the c-fos gene activated more than 10-fold and the CD40L gene activated more than 6-fold. Although CD40L was significantly increased by CC and HWAL, the increase was only about 2-fold. In addition, CC and HWAL did not significantly activate the expression of the c-fos gene. On the other hand, CC elevated the M1 activation marker iNOS, and HWAL elevated the M2 activation marker Ym1 and ARG1 gene expression. In conclusion, MAEK could be used as an immune stimulant because of its ability to activate T cells (elicited c-fos and CD40L gene expression), whereas HWAL could serve as an anti-inflammatory agent because of its differential activation of M2 macrophages.
Kim, Hee Yeon;Kim, Hye Jin;Hwang, Ji Sun;Lee, Won Jun
Journal of Life Science
/
v.24
no.11
/
pp.1180-1186
/
2014
Autophagy, the lysosomal degradation pathway, is an intracellular recycling system that is necessary for the metabolic benefits of exercise and for producing lasting beneficial effects of exercise in various diseases. However, the most recent studies have only examined the effect of a single bout of exercise or resistance exercise on autophagic responses. To determine the differential effects of acute and chronic exercise on the expression of autophagy-related genes in D. melanogaster, white-eyed mutant D. melanogaster were assigned randomly to four groups: control, acute exercise, 2 hr chronic exercise, and 3 hr chronic exercise. The flies were exercised using a mechanized platform known as the Power Tower. Our results revealed that a single bout of exercise resulted in increased mRNA levels of the Atg8a gene (~20%, p<0.05). However, Atg1 and Atg6 mRNA expression were not induced by acute exercise. Transcript levels of Atg6 (~29%, p<0.05) related to the nucleation of autophagosomes were significantly induced by 2 hr of chronic exercise. However, this chronic exercise was not enough to increase Atg1 and Atg8a mRNA expression. On the other hand, 3 hr of exercise for 7 days significantly increased Atg1, Atg6, and Atg8a gene expression-about 57%, 37%, and 71%, respectively (p<0.05). These results suggest that a single bout of exercise is not enough to induce full activation of selected autophagy-related genes in D. melanogaster. Our results demonstrated that chronic regular exercise induced autophagy-related gene expression, suggesting that chronic regular exercise training might be required to activate autophagic responses important for producing beneficial effects of exercise in various diseases.
This study was attempted to investigate antioxidant activities of water and ethanol extract from Rosa multiflora (RM) by in vitro assays measuring 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, 2,2'-azino-di-2-ethyl-benzthiazoline sulphonate (ABTS) radical scavenging activity, reducing power activity, nitric oxide (NO) radical scavenging activity, total phenol and total flavonoid content. The water and ethanol extracts from RM scavenged the DPPH radical and ABTS radical in a dose-dependent manner at the concentration range from 10 to $500{\mu}g/ml$. The DPPH radical scavenging activity of water extract was higher than that of ethanol extract. $IC_{50}$ of DPPH radical scavenging activity of water and ethanol extract were $79.73{\mu}g/ml$ and $145.85{\mu}g/ml$. The reducing power activity of water extract was higher than that of ethanol extract. The nitric oxide (NO) radical scavenging activity of the RM extract was similar to their DPPH radical scavenging activity. $IC_{50}$ of ABTs radical scavenging activity of water and ethanol extract was $79.82{\mu}g/ml$ and $159.03{\mu}g/ml$. The reducing power activity of water extract (0.775) was higher than that of ethanol extract (0.568). Total phenolic content of water extract (140.74 mg/g) was higher than that of the ethanol extracts (37.83 mg/g). Total flavonoid content of water extract (45.31 mg/g) was higher than that of the ethanol extracts (42.68 mg/g). This results suggest that water extract of RM may be useful as potential antioxidant sources.
Wang, Ziyu;Li, Mei;Li, Ke;Son, Beung Gu;Kang, Jum Soon;Park, Young Hoon;Lee, Yong Jae;Kim, Sun Tae;Jung, Jae-Chul;Lee, Young Guen;Choi, Young Whan
Journal of Life Science
/
v.27
no.1
/
pp.57-66
/
2017
Traditional Korean fermented herbal plants are potential sources of new food that promote health, but they are still produced by yeast, fungi or bacteria fermentation. In the present work, mushroom (Paecilomyces tenuipes and Cordyceps militaris) fungal dongchunghacho were used to fermented Glycyrrhiza uralensis Fischer (licorice) or mixed with pupa. The pupa were tested as solid substrates for the production of corcycepin, liquiritin, and liquiritigenin. The fermented substrates were analyzed the content of cordycepin, liquiritin, liquiritigenin, and glycirrhizin productivity and inhibitory activity of NO. The cordycepin content of 70% EtOH extract from the fermented mixture of licorice and 50% pupa with C. militaris increased maximum at 33 times. Pupa was very excellent for the production of cordycepin. The liquiritin content was decreased in all the assays inoculated with P. tenuipes and C. militaris dongchunghachos. The liquiritigenin content was higher when fermented with P. tenuipes than C. militaris. The addition of pupa significantly reduced the liquiritin content and glycyrrhizin production. As a result, the liquiritigenin content increased in fermented P. tenuipes and C. militaris, and liquiritin and glycyrrhizin decreased. The inhibition of NO production in the different ethanolic extracts fermented with licorice and pupa was also significantly increased and higher than that of a nonfermented extract in higher polar solvent extracts. The contents of cordycepin and biological active compounds were altered in accordance with the concentration of pupa and fungi. This study provides basic data for use in developing dongchunghacho fungi as a functional food resource.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.