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Mun, Se Hwan,Kim, Jie Wan,Nah, Seong Su,Ko, Na Young,Lee, Jun Ho,Kim, Ju Dong,Kim, Do Kyun,Kim, Hyuk Soon,Choi, Ji Da,Kim, Soo Hyun,Lee, Chang Keun,Park, Seung Hwa,Kim, Bo Kyung,Kim, Hyung Sik,Kim, Yo Wiley Subscription Services, Inc., A Wiley Company 2009 Vol.60 No.3
<B>Objective</B><P>Interleukin-32 (IL-32) is a recently discovered cytokine that appears to play a critical role in human rheumatoid arthritis (RA). It is highly expressed in synovium and fibroblast-like synoviocytes (FLS) from RA patients, but not in patients with osteoarthritis (OA). This study was undertaken to assess IL-32 levels in RA synovial fluid (SF) and to investigate the secretion and regulation of IL-32 in RA FLS.</P><B>Methods</B><P>FLS and SF were obtained from the joints of RA patients. The secretion and expression of IL-32 and activation of signaling molecules were examined by enzyme-linked immunosorbent assay, immunoblotting, immunoprecipitation, reverse transcriptase–polymerase chain reaction, and small interfering RNA (siRNA) transfection.</P><B>Results</B><P>IL-32 levels were high in RA SF compared with OA SF. Furthermore, RA FLS expressed and secreted IL-32 when stimulated with tumor necrosis factor α (TNFα). TNFα-induced expression of IL-32 was significantly suppressed, in a dose-dependent manner, by inhibitors of Syk, protein kinase Cδ (PKCδ), and JNK and by knockdown of these kinases and c-Jun with siRNA. We also observed that PKCδ mediated the activation of JNK and c-Jun, and experiments using specific inhibitors and siRNA demonstrated that Syk was the upstream kinase for the activation of PKCδ.</P><B>Conclusion</B><P>The present findings suggest that IL-32 may be a newly identified prognostic biomarker in RA, thereby adding valuable knowledge to the understanding of this disease. The results also demonstrate that the production of IL-32 in RA FLS is regulated by Syk/PKCδ-mediated signaling events.</P>
Interleukin-33 stimulates formation of functional osteoclasts from human CD14(+) monocytes.
Mun, Se Hwan,Ko, Na Young,Kim, Hyuk Soon,Kim, Jie Wan,Kim, Do Kyun,Kim, A-Ram,Lee, Seung Hyun,Kim, Yong-Gil,Lee, Chang Keun,Lee, Seoung Hoon,Kim, Bo Kyung,Beaven, Michael A,Kim, Young Mi,Choi, Wahn So Birkhäuser ; Springer 2010 Cellular and molecular life sciences Vol.67 No.22
<P>Interleukin (IL)-33 is a recently described pro-inflammatory cytokine. Here we demonstrate IL-33 as a regulator of functional osteoclasts (OCs) from human CD14(+) monocytes. IL-33 stimulates formation of tartrate-resistant acid phosphatase (TRAP)(+) multinuclear OCs from monocytes. This action was suppressed by anti-ST2 antibody, suggesting that IL-33 acts through its receptor ST2, but not by the receptor activator of NF-κB ligand (RANKL) decoy, osteoprotegerin, or anti-RANKL antibody. IL-33 stimulated activating phosphorylations of signaling molecules in monocytes that are critical for OC development. These included Syk, phospholipase Cγ2, Gab2, MAP kinases, TAK-1, and NF-κB. IL-33 also enhanced expression of OC differentiation factors including TNF-α receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells cytoplasmic 1, c-Fos, c-Src, cathepsin K, and calcitonin receptor. IL-33 eventually induced bone resorption. This study suggests that the osteoclastogenic property of IL-33 is mediated through TRAF6 as well as the immunoreceptor tyrosine-based activation motif-dependent Syk/PLCγ pathway in human CD14(+) monocytes.</P>
박지은(Jie-Eun Park),이성학(Sung-Hak Lee),최재묵(Jae-Mook Choi),김일환(Il-Hwan Kim),김덕열(Deog-Yeor Kim),노현정(Hyun-Jung Noh),김택로(Taekrho Kim),김영훈(Young-Hoon Kim),임지웅(Lim Jee Woong),김진환(Jin-Wan Kim),장준환(Jun-Hwan Chan 한국독성학회 2004 Toxicological Research Vol.20 No.2
To evaluate the genotoxicity of CJ-11555, an anti-cirrhotic agent, the reverse mutation test, chromosomal aberration test and in vivo micronucleus test in rats were performed. In the reverse mutation test, the treatment of CJ-11555 at doses of 33.3, 100, 333, 1000, 3330 and 5000 mg/plate with and without S9 did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli ( E. coli) WP2 uvrA. In chromosomal aberration test, CJ-11555 did not induce structural a chromosomal aberration in Chinese hamster ovary (CHO) cells with and without metabolic activation at all doses. In micronucleus test, CJ-11555 did not induce any statistically significant increases in micronucleated polychromatic erythrocyte (MNPCE) at doses of 500, 1000, and<br/> 2000 mg/kg. These results suggest that CJ-11555 might not have a mutagenic potential under the conditions in this study.
Lee, Jie-Eun,Kim, Kyoung Min,Kim, Lee-Kyung,Kim, Kyong Young,Oh, Tae Jung,Moon, Jae Hoon,Choi, Sung Hee,Lim, Soo,Kim, Sang Wan,Shin, Chan Soo,Jang, Hak Chul Elsevier 2017 Bone Vol.105 No.-
<P><B>Abstract</B></P> <P>Trabecular bone score (TBS) is a parameter of bone quality that has been shown to be related to vertebral fractures. This study aimed to analyze the difference in discriminatory power of TBS for vertebral fractures according to the bone mineral density (BMD) T-score. Areal BMD at the lumbar spine (LS, L1–L4), femur neck (FN) and total hip were assessed using dual x-ray absorptiometry (Discovery W, Hologic, Bedford, MA) in 929 women aged 50years or older. TBS was analyzed using iNsight software (Med-Imaps, Pessac, France). Vertebral fractures were identified on lateral X-ray films of the thoracic and lumbar spine using a semi-quantitative method. The study subjects consisted of 158 subjects (17.0%) with normal BMD, 461 (49.6%) with osteopenia and 310 (33.4%) with osteoporosis. The incident vertebral fractures were observed in 92 (9.9%) subjects, including 59 fractures in osteoporosis, 29 fractures in osteopenia, and only 4 fractures in normal BMD. We stratified study subjects into two groups according to their BMD T-scores, osteoporosis or osteopenia/normal BMD. The logistic regression model showed that LS BMD values per each 1 standard deviation (SD) decrease were significantly associated with increased risk of vertebral fracture in both osteoporosis and osteopenia/normal BMD group with stronger association in osteoporosis group. However, a TBS value that was lower by 1SD was significantly associated with vertebral fracture risk only in the osteopenia/normal BMD group. The TBS use in addition to FN BMD and age also showed significantly better discriminatory power for vertebral fracture only in the osteopenia/normal BMD group, but not osteoporosis group. In conclusion, TBS is significantly associated with vertebral fractures in subjects with osteopenia/normal BMD levels. Additional assessment of bone microarchitecture using TBS is better able to identify women at risk of fracture, in particular, those with relatively higher BMD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TBS and BMD showed a significant positive correlation and the association becomes stronger as BMD increases. </LI> <LI> TBS could identify women at risk of fracture, in particular, those having relatively higher BMD-osteopenia or normal BMD. </LI> <LI> TBS did not show a significant association with risk of vertebral fractures in subjects having osteoporotic BMD levels. </LI> </UL> </P>
박지은(Jie-Eun Park),이성학(Sung-Hak Lee),최재묵(Jae-Mook Choi),김일환(Il-Hwan Kim),김덕열(Deog-Yeor Kim),노현정(Hyun-Jung Noh),김택로(Taekrho Kim),김영훈(Young-Hoon Kim),임지웅(Lim Jee Woong),김진완(Jin-Wan Kim),장준환(Jun-Hwan Chan 한국독성학회 2004 Toxicological Research Vol.20 No.1
To evaluate the genotoxicity of CJ-11555, an anti-cirrhotic agent, the reverse mutation test, chromosomal aberration test and in vivo micronucleus test in rats were performed. In the reverse mutation test, the treatment of CJ-11555 at doses of 33.3, 100, 333, 1000, 3330 and 5000 mg/plate with and without S9 did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli ( E. coli) WP2 uvrA. In chromosomal aberration test, CJ-11555 did not induce structural a chromosomal aberration in Chinese hamster ovary (CHO) cells with and without metabolic activation at all doses. In micronucleus test, CJ-11555 did not induce any statistically significant increases in micronucleated polychromatic erythrocyte (MNPCE) at doses of 500, 1000, and 2000 mg/kg. These results suggest that CJ-11555 might not have a mutagenic potential under the conditions in this study.
Yang Hyo-Joon,Kim Young-Il,Ahn Ji Yong,Choi Kee Don,Kim Sang Gyun,Jeon Seong Woo,Kim Jie-Hyun,Shin Sung Kwan,Lee Hyuk,Lee Wan-Sik,Kim Gwang Ha,Park Jae Myung,Shin Woon Geon,Choi Il Ju 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.4
Background/Aims: The eCura system, a scoring model for stratifying the lymph node metastasis risk after noncurative endoscopic resection for early gastric cancer (EGC), has been internally validated, primarily for differentiated-type EGC. We aimed to externally validate this model for undifferentiated-type EGC. Methods: This multicenter, retrospective cohort study included 634 patients who underwent additional surgery (radical surgery group, n=270) or were followed up without additional treatment (no additional treatment group, n=364) after noncurative endoscopic resection for undifferentiated- type EGC between 2005 and 2015. The lymph node metastasis and survival rates were compared according to the risk categories. Results: For the radical surgery group, the lymph node metastasis rates were 2.6%, 10.9%, and 14.8% for the low-, intermediate-, and high-risk eCura categories, respectively (p for trend=0.003). For the low-, intermediate-, and high-risk categories in the no additional treatment group, the overall survival (92.7%, 68.9%, and 80.0% at 5 years, respectively, p<0.001) and cancer-specific survival rates (99.7%, 94.7%, and 80.0% at 5 years, respectively, p<0.001) differed significantly. In the multivariate analysis, the hazard ratios (95% confidence interval) in the no additional treatment group relative to the radical surgery group were 3.18 (1.41 to 7.17; p=0.005) for overall mortality and 2.60 (0.46 to 14.66; p=0.280) for cancer-specific mortality in the intermediate-tohigh risk category. No such differences were noted in the low-risk category. Conclusions: The eCura system can be applied to undifferentiated-type EGC. Close follow-up without additional treatment might be considered for low-risk patients, while additional surgery is recommended for intermediate- and high-risk patients.
Lee, Jun Ho,Kim, Jie Wan,Ko, Na Young,Mun, Se Hwan,Kim, Do Kyun,Kim, Ju Dong,Won, Hyung Sik,Shin, Hwa Sup,Kim, Hyung Sik,Her, Erk,Kim, Young Mi,Choi, Wahn Soo The Society 2008 Experimental biology and medicine Vol.233 No.10
<P>Complementary and alternative medicines are considered as a promising direction for the development of anti-allergic therapies in oriental countries. We screened approximately 100 oriental herbal medicines for anti-allergic activity. Sophorae flos exhibited the most potent effect on degranulation in antigen-stimulated mast cells. We further investigated the effect of Sophorae flos on the IgE-mediated allergic response in vivo and its mechanism of action in mast cells. Sophorae flos exhibited a significant inhibitory effect on degranulation in antigen-stimulated mast cells with IC(50) values of approximately 31.6 microg/mL (RBL-2H3 mast cells) and approximately 47.8 microg/mL (bone marrow-derived mast cells). Sophorae flos also suppressed the expression and secretion of TNF-alpha and IL-4 in the cells and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. Sophorae flos inhibited the activating phosphorylation of Syk and LAT in mast cells. Further downstream, activating phosphorylation of Akt and the prototypic MAP kinases, namely, p38, ERK1/2, and JNK, were also inhibited. These results suggest that Sophorae flos inhibits the Src family kinase-dependent signaling cascades in mast cells and may thus exert anti-allergic activity.</P>
CJ-11555의 Sprague-Dawely 랫드를 이용한 단회 및 4주 반복경구투여 독성시험
김일환(Il-Hwan Kim),이성학(Sung-Hak Lee),최재묵(Jae-Mook Choi),박지은(Jie-Eun Park),김덕열(Deog-Yeor Kim),노현정(Hyun-Jung Noh),김택로(Taek-Rho Kim),이상호(Sang-Ho Lee),김영훈(Young-Hoon Kim),김진완(Jin-Wan Kim),장준환(Jun-Hwan Chang 한국독성학회 2004 Toxicological Research Vol.20 No.2
This study was to investigate single and repeated-dose toxicities of CJ-11555, an anticirrhotic agent, in Sprague-Dawley (SD) rats. In single-dose oral toxicity study, the test article were<br/> administered once by gavage to males and females at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and CJ-11555 treated group. Therefore, the approximate lethal dose of CJ-11555 was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test article was administered once daily by gavage to<br/> male and female rats at dose levels of 0, 10, 50 and 200 mg/kg/day for 4-weeks. In clinical signs, yellow-colored urine and yellow hair coat were observed in the 50 and 200 mg/kg male and female<br/> groups. In hematology, erythrocyte count and hemoglobin were significantly decreased in the 200mg/kg male and female groups. In serum biochemistry, total cholesterol was significantly increased and aspartate aminotransferase (AST) was significantly decreased in the 50 or 200 mg/kg male and female groups. In histopathological examinations, centrilobular hepatocellular hypertrophy in the liver, congestion and pigmentation in the spleen, hyaline droplets in the kidney were observed in the 50 and 200 mg/kg male and female groups. In toxicokinetic study, CJ-11555 was dose-dependent in systemic exposure and showed better absorption in female with minimum accumulation after multidosing. Based on these results, it was concluded that the 4-week repeated oral dose of CJ-11555<br/> resulted in the suppression of AST activity and centrilobular hepatocellular hypertrophy in both sexes at a dose level of 50 or 200 mg/kg/day. The target organ was estimated to be liver, spleen and male's kidney. The no-observed-adverse-effect level (NOAEL) for CJ-11555 in rats following gavage for at least 4-week is 10 mg/kg/day.