Characterization and anti-tumor activity of saponin-rich fractions of South Korean sea cucumbers (Apostichopus japonicus)

Yu-Lin Dai,Eun-A Kim,Hao-Ming Luo,Yun-Fei Jiang,Jae-Young Oh,Soo-Jin Heo,You-Jin Jeon 제주대학교 해양과학연구소 2020 해양과환경연구소 연구논문집 Vol.44 No.-

In this study, the saponin-rich fractions of five individual (two Red and three Black) sea cucumbers (Apostichopus japonicus) in South Korea were investigated for their antiproliferative effect against HL-60, B16F10, MCF-7, and Hep3B tumor cell lines. The red sea cucumber saponin-rich fraction (SSC) from Jeju Island (JRe) decreased the growth of HL-60 with an IC50 value of 23.55 ± 3.40 lg/mL, which represented the strongest anticancer activity among the extracts. Further, SSC downregulated B-cell lymphoma extra-large (Bcl-xL), while upregulating, to different degrees, Bcl-2-associated X protein (Bax), caspase-9, caspase-3, PARP cleavage, and apoptotic bodies in cancer cells. Evidence for SSC inducing apoptosis via the mitochondria-mediated pathway was found. The contents of SSCs were determined using ultra high-performance liquid chromatography coupled with a quadrupole orbitrap mass spectrometry to comparatively evaluate the regional influence. In West Sea, the total SSC content of A. japonicus was 15.5 mg/g, representing the highest content, while A. japonicus in the South Sea yielded the lowest content at 8 mg/g. The major saponin constituent in SSC was identified as Holotoxin A1, which may the anti-tumor compound in A. japonicus.

한국인 좌심실 비대증 환자들에서 파브리병 선별검사의 의의

박형두,조성윤,이수연,전은석,박승우,이상훈,이상철,최진오,박성지,장성아,김형관,기창석,김종원,진동규,Park, Hyeong-Du,Jo, Seong-Yun,Lee, Su-Yeon,Jeon, Eun-Seok,Park, Seung-U,Lee, Sang-Hun,Lee, Sang-Cheol,Choe, Jin-O,Park, Seong-Ji,Jang, Seong-A,K 대한유전성대사질환학회 2014 대한유전성대사질환학회지 Vol.14 No.2

목적: 파브리병(Fabry disease)은 alpha-galactosidase A의 결핍으로 인하여 리소좀에 globotriaosylceramide(Gb3)가 축적되어 여러 장기에 이상을 일으키는 질병이다. 본 연구에서는 파브리병의 만성 합병증 중 심장 질환을 주로 보이는 환자들, 그 중에서도 좌심실 비대증을 보이는 한국인 환자들을 대상으로 파브리병의 빈도를 알아보고자 하였다. 방법: 좌심실비대증을 진단받은 환자 257명을 연구대상으로 선정하였고, 남성이 172명(평균 56세, 범위 30-81세), 여성이 84명(평균 66세, 범위 45-85세)이었다. 파브리병 선별을 위하여 고성능액체크로마토그래피-탠덤질량분석기를 이용하여 소변 Gb3 농도를 측정하였다. 확진은 형광분석법에 의한 말초혈액의 alpha-galactosidase A 활성도와 염기서열분석법에 의한 GLA 유전자 돌연변이 유무를 검사하여 이루어졌다. 결과: 소변 Gb3 검사에서 cutoff (25 ug/mmoL creatinine)를 초과하는 환자는 4명이었지만, 최종적으로 추가 검사를 통해 진단된 파브리병 환자는 여성 환자 한 명이었다(1/257명, 0.4%). 확진된 환자는 54.3 ug/mmoL creatinine의 Gb3 농도와 15.5 nmole/hr/mg protein (참고범위, $55.2{\pm}12.7nmole/hr/mg$ protein)의 alpha-galactosidase A 활성도를 보였다. GLA 유전자에서는 c.796G>A (p.D266N) 돌연변이가 이형접합체로 관찰되었다. 추가로 시행한 가족검사에서 환자의 딸은 아직 파브리병의 증상을 보이지 않았지만, 엄마와 같은 GLA 돌연변이(c.796G>A)를 가지고 있었으며, alpha-galactosidaseA 활성도는 42.5 nmole/hr/mg protein, 소변 Gb3 농도는 25.5 ug/mmoL creatinine을 나타냈다. 결론: 한국인 좌심실 비대증을 가진 환자들에서 파브리병의 유병율은 0.4%였다. 유병율이 낮아 보임에도 불구하고, 파브리병 진단 전 환자와 가족 구성원을 발견할 수 있는 장점 덕분에 선별검사의 의의가 있는 것으로 사료된다. Objectives: Fabry disease (FD) is a lysosomal storage disease caused by the inappropriate accumulation of globotriaosylceramide (Gb3) in tissues due to a deficiency in the enzyme ${\alpha}$-galactosidase A. Hypertrophic cardiomyopathy is one of the chronic complications of FD. We tried to evaluate the prevalence of Fabry disease in the Korean patients with left ventricular hypertrophy (LVH). Methods: A total of 257 patients with LVH were recruited and they were 172 males (mean 56 years, range 30-81 years) and 84 females (mean 66 years, range 45-85 years). Urinary Gb3 was used to screen FD by high performance liquid chromatography-tandem mass spectrometry. Confirmatory tests were done by alpha-galactosidaseA activity using fluorometric assay and by GLA mutation analysis using sequencing. Results: Four patients were screening positive by urinary Gb3 analysis (cutoff, 25 ug/mmol creatinine). But, one female patient was diagnosed with FD confirmed by enzyme analysis in leukocytes as well as by genetic analysis (1/257 patients, 0.4%). She showed 54.3 ug/mmoL creatinine of Gb3 and 15.5 nmole/hr/mg protein (reference range, $55.2{\pm}12.7nmole/hr/mg$ protein) of alphagalactosidase A activity. And she had a heterozygous GLA mutation of c.796G>A (p.D266N). Her daughter was found to be a carrier for FD confirmed by GLA mutation analysis. Asymptomatic carrier showed 25.5ug/mmol creatinine of Gb3 and 42.5 nmole/hr/mg protein (reference range, $55.2{\pm}12.7nmole/hr/mg$ protein) of alpha-galactosidase A activity. Conclusions: The prevalence of FD in Koran patients with LVH was detected as 0.4%. Although the prevalence seems to be low, screening studies are of great importance for detecting hidden cases as well as for identifying other effected family members.

Intestinal Nematodes from Small Mammals Captured near the Demilitarized Zone, Gyeonggi Province, Republic of Korea

Deok-Gyu Kim,Jae-Hwan Park,Jae-Lip Kim,Bong-Kwang Jung,Sarah Jiyoun Jeon,Hyemi Lim,Mi Youn Lee,Eun-Hee Shin,Terry A. Klein,Heung-Chul Kim,Sung-Tae Chong,Jin-Won Song,Luck-Ju Baek,Jong-Yil Chai 대한기생충학열대의학회 2015 The Korean Journal of Parasitology Vol.53 No.1

A total of 1,708 small mammals (1,617 rodents and 91 soricomorphs), including Apodemus agrarius (n = 1,400), Microtus fortis (167), Crocidura lasiura (91), Mus musculus (32), Myodes (= Eothenomys) regulus (9), Micromys minutus (6), and Tscherskia (= Cricetulus) triton (3), were live-trapped at US/Republic of Korea (ROK) military training sites near the demilitarized zone (DMZ) of Paju, Pocheon, and Yeoncheon, Gyeonggi Province from December 2004 to December 2009. Small mammals were examined for their intestinal nematodes by necropsy. A total of 1,617 rodents (100%) and 91 (100%) soricomorphs were infected with at least 1 nematode species, including Nippostrongylus brasiliensis, Heligmosomoides polygyrus, Syphacia obvelata, Heterakis spumosa, Protospirura muris, Capillaria spp., Trichuris muris, Rictularia affinis, and an unidentified species. N. brasiliensis was the most common species infecting small mammals (1,060; 62.1%) followed by H. polygyrus (617; 36.1%), S. obvelata (370; 21.7%), H. spumosa (314; 18.4%), P. muris (123; 7.2%), and Capillaria spp. (59; 3.5%). Low infection rates (0.1-0.8%) were observed for T. muris, R. affinis, and an unidentified species. The number of recovered worms was highest for N. brasiliensis (21,623 worms; mean 20.4 worms/infected specimen) followed by S. obvelata (9,235; 25.0 worms), H. polygyrus (4,122; 6.7 worms), and H. spumosa (1,160; 3.7 worms). A. agrarius demonstrated the highest prevalence for N. brasiliensis (70.9%), followed by M. minutus (50.0%), T. triton (33.3%), M. fortis (28.1%), M. musculus (15.6%), C. lasiura (13.2%), and M. regulus (0%). This is the first report of nematode infections in small mammals captured near the DMZ in ROK.

남한 내 북한이탈주민들의 3년간 사회의식 변화 및 생활 만족도에 대한 추적연구

전우택,유시은,조영아,홍창형,엄진섭,서승원 大韓神經精神醫學會 2006 신경정신의학 Vol.45 No.3

Objectives : The aim of this study was to examine the change in attitudes and satisfaction level of North Korean defectors in South Korea over a 3 year period (2001-2004). Methods : In our first study in 2001, a total of 200 detectors were interviewed. In the follow up study after 3 years, 151 defectors were re-interviewed by an in-person interview. Results : The level of satisfaction to the governmental support policy to defectors decreased significantly. However, the general level of satisfaction increased slightly (from 3.52 to 3.56 ; 5-score scale). This shows that North Korean defectors are stably adapting to South Korean society. The level of satisfaction significantly correlated with the defectors' confusion of the different value systems, the defectors' understanding of the South Korean people, satisfaction with their physical and mental health, and the Prejudice of South Korean people to defectors. In terms of the attitudes, the type of schooling, the military service and the communist party membership in North Korea were not related to the change in attitude. However, there was a significant correlation with gender and age. Women showed a greater change in attitude compared to men. Older people had difficulty in understanding the South Korean people, but they showed little psychological affiliation to North Korea. Moreover, they showed a high level of satisfaction with the economic situation in South Korea and had an optimistic viewpoint for their future than younger people. Even though many defectors attended churches, religion was not associated with the level of satisfaction or their change in attitude. Conclusion : The factors that influence the level of satisfaction and attitudes of North Korean defectors have changed over 3 years. Therefore, the government, nongovernmental organizations (NGOs) associated with defectors and the churches need to be more sensitive to these changes and make plans to support the adaptation of defectors to South Korean society.

Inappropriate Gonadotropin Secretion in Polycystic Ovary Syndrome: The Relationship with Clinical, Hormonal and Metabolic Characteristics

( A Ra Shim ),( Yu Im Hwang ),( Kyung Jin Lim ),( Young Mi Choi ),( Young Eun Jeon ),( Seok Kyo Seo ),( Si Hyun Cho ),( Young Sik Choi ),( Byung Seok Lee ) 대한산부인과학회 2011 Obstetrics & Gynecology Science Vol.54 No.11

Objective To evaluate the clinical, hormonal and metabolic characteristics according to luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio in women with polycystic ovary syndrome (PCOS). Methods A total of 225 women with PCOS were included in this study. They were divided into two groups according to LH/FSH ratio; group A (LH/FSH < 2, n=160) and group B (LH/FSH > 2, n=65). We compared clinical, hormonal and metabolic characteristics including age at menarche, body mass index (BMI), blood pressures, ovarian volume, and serum androgen levels between the two groups. Serum glucose and insulin levels, fasting glucose/insulin ratio, homeostatic model assessment of insulin resistance (HOMA-IR), and lipid profi les were also compared between the two groups. Pearson correlation coeffi cients were used to evaluate correlation between the LH/FSH ratio and various parameters. Results Age of menarche in the group B was signifi cantly later than that in the group A. BMI, waist-hip ratio and blood pressures were signifi cantly lower in the group B compared to those of the group A. Ovarian volume and serum levels of LH, estradiol, total testosterone, sex-hormone binding globulin, 17-hydroxyprogesterone (OHP), and high density lipoprotein were signifi cantly higher in the group B. Postprandial 2 hours glucose, insulin and HOMA-IR were signifi cantly higher in the group A. After adjustment of BMI, the LH/FSH ratio was signifi cantly positively correlated with age at menarche, ovarian volume, total testosterone levels, and 17-OHP levels. Conclusion The inappropriate gonadotropin secretion may be negatively correlated with BMI, and positively with age of menarche and increased ovarian androgen production irrespective of BMI in women with PCOS. However, it may not be associated with metabolic characteristics.

Energy Transfer from Ethidium to Cationic Porphyrins Mediated by DNA and Synthetic Polynucleotides at Low Binding Densities

Jung, Jin-A,Jeon, Sun-Hee,Han, Sung-Wook,Lee, Gil-Jun,Bae, In-Ho,Kim, Seog-K. Korean Chemical Society 2011 Bulletin of the Korean Chemical Society Vol.32 No.8

The fluorescence of ethidium bound to DNA, poly[d(A-T)$_2$], and poly[d(G-C)$_2$] at a [ethidium]/[DNA] ratio of 0.005 was quenched by porphyrins when both ethidium and the porphyrins simultaneously bound to the same polynucleotide. The quenching was tested using the "inner sphere" and the "Forster resonance energy transfer" (FRET) models, with the latter found to contribute, at least in part, to the quenching. Meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (TMPyP) exhibited a higher quenching and FRET efficiency than cis-bis(N-methylpyridinium-4-yl)porphyrin (BMPyP) for all of the tested DNA and polynucleotides, demonstrating that energy transfer efficiency is affected by the number of positive charges of porphyrins.

남한 내 북한이탈주민의 3년간 사회적응 추적 연구 : 2001년부터 2004년까지 생활과 교육을 중심으로 With prioty given to life of North Korea defectors from 2001 to 2004

유시은,전우택,조영아,홍창형,엄진섭 연세대학교 통일연구원 2005 통일연구 Vol.9 No.1

Purpose of this study : In 2001, this study that investigate actual conditions about adaptation degree of Korean social life of the North Korean defectors was carried out to 151 people that succeed in chases among 200 the North Korea defectors answer in study. Purpose of this study is as following. First, we wished to search change aspect of actual conditions about South Korea society adaptation of the North Korean defectors who take part in the first investigation for past 3 years. Second, we wished to search difference of adaptation aspect by populational and social element. Third, We wished to suggest things that can be beaconed to efficient support policy of government or private organization and successful South Korea social adaptation method which support the North Korean defectors on the basis of study finding about change of adaptation aspect of the North Korea defectors. Methods of Study : We designated 200 Panels to study and survey actual adaptation conditions of the North Korean defectors on South Korea society synthetically and for long-term. So, chasing about 151 people was possible in 2004. We are fertilized and supplement the questionnaire forming in 2001 and composed the new questionnaires to part of a life, mental state, Body and health. This study among them investigated a standard of living of the North Korean defectors. In this process, interviewer directly asked and recorded questions to reduce individual variation of people who receive interview. Study Results : Government's residence support policy about North Korean secession inhabitants was generally attained as effective and suitable for North Korean inhabitants' early South Korea settlement. Only, government need to discuss about North Korea secession inhabitants' residence support more variously for long-term. Second, education should be supported more actively and variously. Suitable point of education for their needs should make a effect of vocational training or education maximize. This is a very important part. Third, they need guidance and education that can receive more easily law support. Fourth, medical supports and health cares should be achieved continuously and systematically to them since they arrived in South Korea. To supports and studies North Korean secession inhabitants has the large significance to gain a foothold about reunification of North and south. Their South Korea society adaptation is becoming topic of conversation among South Korean. An atmosphere of unity is elated. And interest degrees about North Korean are actually rising as exchanges between South and North Korean is activated. Therefore, the adaptation study about North Korean secession inhabitants will have to be expanded in studies for South Korean, not to be limited in studies for North Korean.

Optimization of Agrobacterium tumefaciens-Mediated Transformation of Xylaria grammica EL000614, an Endolichenic Fungus Producing Grammicin

( Min-hye Jeong ),( Jung A. Kim ),( Seogchan Kang ),( Eu Ddeum Choi ),( Youngmin Kim ),( Yerim Lee ),( Mi Jin Jeon ),( Nan Hee Yu ),( Ae Ran Park ),( Jin-cheol Kim ),( Soonok Kim ),( Sook-young Park ) 한국균학회 2021 Mycobiology Vol.49 No.5

An endolichenic fungus Xylaria grammica EL000614 produces grammicin, a potent nematicidal pyrone derivative that can serve as a new control option for root-knot nematodes. We optimized an Agrobacterium tumefaciens-mediated transformation (ATMT) protocol for X. grammica to support genetic studies. Transformants were successfully generated after co-cultivation of homogenized young mycelia of X. grammica with A. tumefaciens strain AGL-1 carrying a binary vector that contains the bacterial hygromycin B phosphotransferase (hph) gene and the eGFP gene in T-DNA. The resulting transformants were mitotically stable, and PCR analysis showed the integratin of both genes in the genome of transformants. Expression of eGFP was confirmed via fluorescence microscopy. Southern analysis showed that 131 (78.9%) out of 166 transformants contained a single T-DNA insertion. Crucial factors for producing predominantly single T-DNA transformants include 48 h of co-cultivation, pretreatment of A. tumefaciens cells with acetosyringone before co-cultivation, and using freshly prepared mycelia. The established ATMT protocol offers an efficient tool for random insertional mutagenesis and gene transfer in studying the biology and ecology of X. grammica.

Beijing urban particulate matter-induced injury and inflammation in human lung epithelial cells and the protective effects of fucosterol from <i>Sargassum binderi</i> (Sonder ex J. Agardh)

Fernando, I.P. Shanura,Jayawardena, Thilina U.,Kim, Hyun-Soo,Lee, Won Woo,Vaas, A.P.J.P.,De Silva, H.I.C.,Abayaweera, G.S.,Nanayakkara, C.M.,Abeytunga, D.T.U.,Lee, Dae-Sung,Jeon, You-Jin Academic Press 2019 Environmental research Vol.172 No.-

<P><B>Abstract</B></P> <P>Particulate matter (PM) air pollution has gradually become a widespread problem in East Asia. PM may cause unfamiliar inflammatory responses, oxidative stress, and pulmonary tissue damage, and a comprehensive understanding of the underlying mechanisms is required in order to develop effective anti-inflammatory agents. In this study, fine dust collected from Beijing, China (CPM) (size < PM13 with majority < PM2.5) was evaluated for its oxidative stress- and inflammation-inducing effects, which cause cell damage, in A459 human lung epithelial cells. Oxidative stress was marked by an increase in intracellular ROS levels and the production of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO-1). Upon induction of oxidative stress, a marked increase was observed in the expression of key inflammatory mediators such as COX-2 and PGE<SUB>2</SUB> and the pro-inflammatory cytokines TNF-α and IL-6 via NF-kB and MAPK pathways. Cellular damage was marked by a reduction in viability, increased lactate dehydrogenase (LDH) release, formation of apoptotic and necrotic bodies, accumulation of sub-G1 phase cells, and DNA damage. Apoptosis was found to be mediated via the activation of caspases through the mitochondria-mediated pathway. Fucosterol, purified from the brown alga <I>Sargassum binderi</I> (Sonder ex J. Agardh) by bio-assay-guided fractionation and purification, exhibited potential therapeutic effects against CPM-induced detrimental effects. Further studies could focus on developing fucosterol, in forms such as steroidal inhalers, against PM-induced pulmonary tissue inflammation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Fine dust air pollution is a major reason of pulmonary complications in East Asia. </LI> <LI> Dust particles induce oxidative stress and inflammation damaging the lung epithelial cells. </LI> <LI> Fucosterol suppressed the dust induced cell damage by inhibiting oxidative stress and inflammation. </LI> <LI> Fucosterol may have beneficial effects in alleviating adverse respiratory effects of air pollution. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

High antiangiogenic and low anticoagulant efficacy of orally active low molecular weight heparin derivatives

Park, J.W.,Jeon, O.C.,Kim, S.K.,Al-Hilal, T.A.,Jin, S.J.,Moon, H.T.,Yang, V.C.,Kim, S.Y.,Byun, Y. Elsevier Science Publishers 2010 Journal of controlled release Vol.148 No.3

Heparin, an anticoagulant that is widely used clinically, is also known to bind to several kinds of proteins through electrostatic interactions because of its polyanionic character. These interactions are mediated by the physicochemical properties of heparin such as sequence composition, sulfation patterns, charge distribution, overall charge density, and molecular size. Although this electrostatic character mediates its binding to many proteins related with tumor progression, thereby providing its antiangiogenic property, the administration of heparin for treating cancer is limited in clinical applications due to several drawbacks, such as its low oral absorption, unsatisfactory therapeutic effects, and strong anticoagulant activity which induces hemorrhaging. Here, we evaluated novel, orally active, low molecular weight heparin (LMWH) derivatives (LHD) conjugated with deoxycholic acid (DOCA) that show reduced anticoagulant activity and enhanced antiangiogenic activity. The chemical conjugate of LMWH and DOCA was synthesized by conjugating the amine group of N-deoxycholylethylamine (EtDOCA) with the carboxylic groups of heparin at various DOCA conjugation ratios. The LMWH-DOCA conjugate series (LHD1, LHD1.5, LHD2, and LHD4) were further formulated with poloxamer 407 as a solubilizer for oral administration. An in vitro endothelial tubular formation and in vivo Matrigel plug assay were performed to verify the antiangiogenic potential of LHD. Finally, we evaluated tumor growth inhibition of oral LHD administration in a SCC7 model as well as in A549 human cancer cell lines in a mouse xenograft model. Increasing DOCA conjugation ratios showed decreased anticoagulant activity, eventually to zero. LHD could block angiogenesis in the tubular formation assay and the Matrigel plug assay. In particular, oral administration of LHD4, which has 4 molecules of DOCA per mole of LMWH, inhibited tumor growth in SCC7 mice model as well as A549 mice xenograft model. LHD4 was orally absorbable, showed minimal anticoagulant activity and inhibits tumor growth via antiangiogenesis. These findings demonstrate the therapeutic potential of LHD4 as a new oral anti-cancer drug.