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Ligand‐activated interaction of PPARδ with c‐Myc governs the tumorigenicity of breast cancer
Ham, Sun Ah,Kim, Eunsu,Yoo, Taesik,Lee, Won Jin,Youn, Ju Ho,Choi, Mi‐,Jung,Han, Sung Gu,Lee, Chi‐,Ho,Paek, Kyung Shin,Hwang, Jung Seok,Seo, Han Geuk Alan R. Liss, Inc 2018 International journal of cancer Vol.143 No.11
<P>Peroxisome proliferator‐activated receptor (PPAR) δ is a promising therapeutic target in metabolic and inflammatory disorders. However, its role in oncogenesis is controversial, and its therapeutic potential remains to be determined. In our study, we show that ligand‐activated PPARδ forms a complex with the proto‐oncogene product c‐Myc. The interaction of PPARδ with c‐Myc affected the transcriptional activity of c‐Myc and the expression of its target genes. The PPARδ‐dependent regulation of c‐Myc activity was associated with decreased tumorigenicity in breast cancer cells. Administration of the PPARδ ligand GW501516 inhibited tumor growth in xenograft model mice bearing MDA‐MB‐231 cells stably expressing wild‐type PPARδ, but not those expressing dominant‐negative PPARδ, by interfering with c‐Myc function through protein–protein interaction. Our results indicating that PPARδ forms an antitumorigenic complex with c‐Myc in the presence of ligand suggest a potential role of PPARδ in breast cancer development.</P>
Ham, Sung-Il,Song, Eun-Ha,Yang, San-Duk,Thong, Chin-Ting,Rhie, Arang,Galbadrakh, Bulgan,Lee, Kyung-Eun,Park, Hyun-Seok,Lee, San-Ho Korea Genome Organization 2009 Genomics & informatics Vol.7 No.3
The characteristics of metabolic pathways make them particularly amenable to layered graph drawing methods. This paper presents a visual Java-based tool for drawing and annotating biological pathways in two- and a-half dimensions (2.5D) as an alternative to three-dimensional (3D) visualizations. Such visualization allows user to display different groups of clustered nodes, in different parallel planes, and to see a detailed view of a group of objects in focus and its place in the context of the whole system. This tool is an extended version of J2dPathway.
γ-Aminobutyric Acid Metabolism in Plant under Environment Stressses
Ham Tae-ho,Chu Sang-ho,Han Sang Jun,Ryu Su-Noh 韓國作物學會 2012 한국작물학회지 Vol.57 No.2
~gamma -Aminobutyric acid (GABA) is a non-protein amino acid that is widely distributed in plant and animal kingdom. GABA is found in tissues of the central nervous system (CNS) in animals. GABA functions as a the major inhibitory neurotransmitter in the CNS by acting through the GABA receptors. Clinical studies have revealed the relationship between an increased intake of GABA or analogues with several health benefits, including lowering of blood pressure in mildly hypertensive animals and humans. Furthermore, GABA would also has an inhibitory effect on cancer cell proliferation, stimulates cancer cell apoptosis and plays a role in alcohol-associated diseases and schizophrenia. In plants, interest in the GABA emerged mainly from experimental observations that GABA is largely and rapidly produced in large amounts in response to biotic and abiotic stresses. In this study, we speculated the properties and metabolism of GABA in plant and functions in relation to the responses to environmental stresses.
Methoxsalen supplementation attenuates bone loss and inflammatory response in ovariectomized mice
Ham, Ju Ri,Choi, Ra-Yeong,Yee, Sung-Tae,Hwang, Yun-Ho,Kim, Myung-Joo,Lee, Mi-Kyung Elsevier 2017 Chemico-biological interactions Vol.278 No.-
<P><B>Abstract</B></P> <P>Methoxsalen (MTS) is a natural bioactive compound found in a variety of plants that has many known biofunctions; however, its effects on osteoporosis and related mechanisms are not clear. This study examined whether MTS exhibited preventive effects against postmenopausal osteoporosis. Female C3H/HeN mice were divided into four groups: Sham, ovariectomy (OVX), OVX with MTS (0.02% in diet), and OVX with estradiol (0.03 μg/day, s.c). After 6 weeks, MTS supplementation significantly increased femur bone mineral density and bone surface along with bone surface/total volume. MTS significantly elevated the levels of serum formation markers (estradiol, osteocalcin and bone-alkaline phosphatase) such as estradiol in OVX mice. Tartrate resistant acid phosphatase staining revealed that MTS suppressed osteoclast numbers and formation in femur tissues compared with the OVX group. Supplementation of MTS slightly up-regulated osteoblastogenesis-related genes (<I>Runx-2</I>, <I>osterix</I>, <I>osteocalcin</I>, and <I>Alp</I>) expression, whereas it significantly down-regulated inflammatory genes (<I>Nfκb</I> and <I>Il6</I>) expression in femur tissue compared with the OVX group. These results indicate that MTS supplementation effectively prevented OVX-induced osteoporosis via enhancement of bone formation and suppression of inflammatory response in OVX mice. Our study provides valid scientific information regarding the development and application of MTS as a food ingredient, a food supplement or an alternative agent for preventing postmenopausal osteoporosis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Methoxsalen improves bone mineral density in ovariectomized mice. </LI> <LI> Methoxsalen increased serum bone-ALP, osteocalcin and estradiol levels. </LI> <LI> Methoxsalen down-regulated <I>Il6</I> and <I>Nfκb</I> gene expression in femur. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Enhancement of potency and stability of human extracellular superoxide dismutase
( Sung Hwan Kim ),( Hae Young Kim ),( Jung Ho Kim ),( Jung Hye Choi ),( Won Kook Ham ),( Yoon Jae Jeon ),( Hara Kang ),( Tae Yoon Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.2
Cells express several antioxidant enzymes to scavenge reactive oxygen species (ROS) responsible for oxidative damages and various human diseases. Therefore, antioxidant enzymes are considered biomedicine candidates. Among them, extracellular superoxide dismutase (SOD3) had showed prominent efficacy against asthma and inflammation. Despite its advantages as a biomedicine, the difficulty in obtaining large quantity of active recombinant human SOD3 (rhSOD3) has limited its clinical applications. We found that a significant fraction of overexpressed rhSOD3 was composed of the inactive apo-enzyme and its potency against inflammation depended on the rate of metal incorporation. Also, purified rhSOD3 was unstable and lost its activity very quickly. Here, we suggest an ideal preparative method to express, purify, and store highly active rhSOD3. The enzymatic activity of rhSOD3 was maximized by incorporating metal ions into rhSOD3 after purification. Also, albumin or polyethylene glycol prevented rapid inactivation or degradation of rhSOD3 during preparative procedures and long-term storage. [BMB Reports 2015; 48(2): 91-96]
Ham, Mira,Choe, Sung Sik,Shin, Kyung Cheul,Choi, Goun,Kim, Ji-Won,Noh, Jung-Ran,Kim, Yong-Hoon,Ryu, Je-won,Yoon, Kun-Ho,Lee, Chul-Ho,Kim, Jae Bum American Diabetes Association 2016 Diabetes Vol.65 No.9
<P>Glucose-6-phosphate dehydrogenase (G6PD), a rate limiting enzyme of the pentose phosphate pathway, plays important roles in redox regulation and de novo lipogenesis. It was recently demonstrated that aberrant upregulation of G6PD in obese adipose tissue mediates insulin resistance as a result of imbalanced energy metabolism and oxidative stress. It remains elusive, however, whether inhibition of G6PD in vivo may relieve obesity-induced insulin resistance. In this study we showed that a hematopoietic G6PD defect alleviates insulin resistance in obesity, accompanied by reduced adipose tissue inflammation. Compared with wild-type littermates, G6PD-deficient mutant (G6PD(mut)) mice were glucose tolerant upon high-fat-diet (HFD) feeding. Intriguingly, the expression of NADPH oxidase genes to produce reactive oxygen species was alleviated, whereas that of antioxidant genes was enhanced in the adipose tissue of HFD-fed G6PD(mut) mice. In diet-induced obesity (DIO), the adipose tissue of G6PDmut mice decreased the expression of inflammatory cytokines, accompanied by downregulated proinflammatory macrophages. Accordingly, macrophages from G6PD(mut) mice greatly suppressed Iipopolysaccharide-induced proinflammatory signaling cascades, leading to enhanced insulin sensitivity in adipocytes and hepatocytes. Furthermore, adoptive transfer of G6PD(mut) bone marrow to wild-type mice attenuated adipose tissue inflammation and improved glucose tolerance in DIO. Collectively, these data suggest that inhibition of macrophage G6PD would ameliorate insulin resistance in obesity through suppression of proinflammatory responses.</P>
Ham, Won Sik,Park, Sung Yul,Rha, Koon Ho,Kim, Won Tae,Choi, Young Deuk Mary Ann Liebert 2009 Journal of Laparoendoscopic & Advanced Surgical Te Vol.19 No.3
<P>OBJECTIVES: The aim of this study was to compare the outcomes of robotic prostatectomy (RP) in patients with clinically localized or locally advanced prostate cancer (PC). PATIENTS AND METHODS: Between July 2005 and February 2008, we performed RP in 357 patients by using the da Vinci robot system and a transperitoneal approach. We defined locally advanced PC as cases with a clinical T-stage >/=T3a with any serum prostate-specific antigen (PSA) or Gleason score. Among the 321 men not treated with neoadjuvant hormonal therapy, 200 patients had clinically localized PC and 121 patients had locally advanced PC. We compared perioperative variables and early surgical outcomes between the two groups. RESULTS: Although advanced PC patients had significantly higher mean preoperative PSA levels, prostatectomy Gleason scores, and extracapsular extension rates, there were no significant differences in mean operation time, estimated blood loss, duration of bladder catheterization, hospital stay, or initiation of a regular postoperative diet between the two groups. Except for some early cases, a bilateral extended lymphadenectomy was performed without difficulty in both groups. Although both the frequency of lymph node invasion and the positive surgical margin rates were higher in the advanced PC patients, the positive surgical margin rate (48.8%) in the present study was similar to those of open radical retropubic prostatectomy in other studies. The overall complication rate did not differ between the two groups. Two intraoperative rectal injuries occurred in patients with locally advanced PC and were closed primarily without specific problems, except for 1 case. CONCLUSIONS: Our results suggest that RP may be performed safely on patients with locally advanced PC.</P>