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Bioinformatic analyses reveal the prognostic significance and potential role of ankyrin 3 (ANK3) in kidney renal clear cell carcinoma

  • Keerakarn Somsuan;Siripat Aluksanasuwan
    • Genomics & Informatics
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    • v.21 no.2
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    • pp.22.1-22.15
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    • 2023
  • Kidney renal clear cell carcinoma (KIRC) is one of the most aggressive cancer type of the urinary system. Metastatic KIRC patients have poor prognosis and limited therapeutic options. Ankyrin 3 (ANK3) is a scaffold protein that plays important roles in maintaining physiological function of the kidney and its alteration is implicated in many cancers. In this study, we investigated differential expression of ANK3 in KIRC using GEPIA2, UALCAN, and HPA databases. Survival analysis was performed by GEPIA2, Kaplan-Meier plotter, and OS-kirc databases. Genetic alterations of ANK3 in KIRC were assessed using cBioPortal database. Interaction network and functional enrichment analyses of ANK3-correlated genes in KIRC were performed using GeneMANIA and Shiny GO, respectively. Finally, the TIMER2.0 database was used to assess correlation between ANK3 expression and immune infiltration in KIRC. We found that ANK3 expression was significantly decreased in KIRC compared to normal tissues. The KIRC patients with low ANK3 expression had poorer survival outcomes than those with high ANK3 expression. ANK3 mutations were found in 2.4% of KIRC patients and were frequently co-mutated with several genes with a prognostic significance. ANK3-correlated genes were significantly enriched in various biological processes, mainly involved in peroxisome proliferator-activated receptor (PPAR) signaling pathway, in which positive correlations of ANK3 with PPARA and PPARG expressions were confirmed. Expression of ANK3 in KIRC was significantly correlated with infiltration level of B cell, CD8+ T cell, macrophage, and neutrophil. These findings suggested that ANK3 could serve as a prognostic biomarker and promising therapeutic target for KIRC.

DA-6034 ameliorates hepatic steatosis and inflammation in high fat diet-induced obese mice

  • Hong Min Kim;Mi-Hye Kwon;Eun Soo Lee;Kyung Bong Ha;Choon Hee Chung
    • Journal of Yeungnam Medical Science
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    • v.41 no.2
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    • pp.103-112
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    • 2024
  • Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation. Methods: Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW 264.7 cells. Results: DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8+ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages. Conclusion: Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.

Twenty-year Experience of Mitral Valve Replacement with the St. Jude Medical Mechanical Valve Prosthesis (St. Jude 기계 판막을 이용한 승모판막 치환술의 20년 장기성적)

  • Seo Yeon-Ho;Kim Kong-Soo;Jo Jung-Ku
    • Journal of Chest Surgery
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    • v.39 no.7 s.264
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    • pp.527-533
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    • 2006
  • Background: A retrospective study was conducted to analyze the results of St. Jude Medical mitral valve replacement at the Chonbuk National University Hospital since the initial implant in May 1984. Material and Method: Between May of 1984 and December of 1996, 95 patients underwent MVR with the St. Jude Medical mechanical valve prosthesis at Department of Medical Science of Chonbuk National University Hospital and follow-up ended in May of 2004. Result: Age ranged from 19 to 69 years. Follow-up (mean${\pm}$standard deviation) averaged $10.6{\pm}4.2\;year$. Thirty-day operative mortality was 4.2% (4/95). Nine late deaths have occurred and actuarial survival was $90.5{\pm}3.0%,\;87.9{\pm}3.4%\;and\;83.2{\pm}4.6%$ at 5, 10 and 20 years, respectively. Probability of freedom from valve-rotated death was $95.5{\pm}2.1%,\;94.3{\pm}2.4%\;and\;91.0{\pm}3.9%$ at 5, 10 and 20 years, respectively. Seven patients have sustained thromboembolic events (1,05%/patient-year). Fifteen patients had anticoagulation related hemorrhage (3.56%/patient-year). There was no structural valve deterioration. Probability of freedom from all complications was $82.0{\pm}3.9%,\;71.3{\pm}4.8%\;and\;42.4{\pm}10.5%$ at 5, 10 and 20 years, respectively. Conclusion: We confirm the effective and excellent durability of the St. Jude Medical prosthesis in the mitral position with a low event rate at long-term follow-up. It also demonstrates the commonly encountered practical difficulty of adjusting the anti-coagulation protocol in patients with prosthetic mitral valves.

A Comparative Study on the Immunizing and Anti-cancer Effect of the Root and the Aerial Part of Peucedanum Japonicum Thunb (갯기름나물의 근(根)과 경엽(莖葉)의 면역 및 항암 활성 비교연구)

  • Cho, Yong-Ho
    • Korean Journal of Korean Medical Institute of Dermatology and Aesthetics
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    • v.1 no.1
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    • pp.127-144
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    • 2005
  • This study compared the activity of the aerial part of P. japonicum with its root in order to examine the possibility of the medicinal use of the aerial part, which has not been used as medicine, in substitute for the root that has traditionally been used as medicine. For this purpose, the author measured the proliferation of Human $CD4^-$ T cells, which are related to immunity, the differentiation of HL-60 cells, and the contents of IL-6, IgE and $TNF-{\alpha}$ and compared their anti-cancer effect on Hep3B and A549 cells. The results of this study are as follows: 1. As for Human $CD4^-$ T cells, $1.0\;g/{\ell}$ methanol extract from the aerial part promoted the proliferation of the cells 1.8 times higher while $1.0\;g/{\ell}$ methanol extract from the root did by 1.76 times higher compared to the control group. 2. As for HL-60 cells, methanol extract and water extract from the aerial part showed differentiation 1.14 times higher and 1.12 times higher respectively while methanol extract and water extract from the root did 1.14 times higher and 1.07 times higher compared to tile control group. 3. Cell density was highest on Day 4 of culture in all samples, Methanol extracts from the aerial part and the root showed activities of $7.9{\times}10^3\;cells/m{\ell}$ and $7.5{\times}10^3\;cells/m{\ell}$ respectively, and water extracts from the aerial part and the root did activities of $5.3{\times}10^3\;cells/m{\ell}$ and $6.1{\times}10^3\;cells/m{\ell}$. 4. The secretion of IL-6 was highest on Day 4 of culture. Methanol extracts from the aerial part and the root showed secretions of $6.7{\times}10^{-3}\;pg/cells/m{\ell}$ and $7.2{\times}10^{-3}\;pg/cells/m{\ell}$ respectively, and water extracts from the aerial part and the root did secretions of as high as $7.0{\times}10^{-3}\;pg/cells/m{\ell}$ and $6.0{\times}10^{-3}\;pg/cells/m{\ell}$. 5. As for the production of IgE, water extract from the root effectively inhibited the product at $1,000\;{\mu}g/m{\ell}$, methanol extract from the root at $10\;{\mu}g/m{\ell}$ and $100\;{\mu}g/m{\ell}$, water extract from the aerial at $1,000\;{\mu}g/m{\ell}$, and methanol extract from the aerial part at $1,000\;{\mu}g/m{\ell}$. 6. According to the result of measuring the content of $TNF-{\alpha}$, methanol extracts from the root and the aerial part showed inhibition effect at $10\;{\mu}g/m{\ell}$, $100\;{\mu}g/m{\ell}$ and $1,000\;{\mu}g/m{\ell}$. 7. As for liver cancer cell Hep3B, $1.0\;g/{\ell}$ methanol extracts from the root and the aerial part showed inhibition effects of 78% and 70% respectively, and $1.0\;g/{\ell}$ water extracts from the root and the aerial part did inhibition effects of 56% and 59%. 8. As for lung cancer cell A549, $1.0\;g/{\ell}$ methanol extracts from the root and the aerial part showed inhibition effects of 75% and 70% respectively, and $1.0\;g/{\ell}$ water extracts from the root and the aerial part did inhibition effects of 48% and 45%. The results of this study presented above show that the aerial part of P. japonicum has immunizing and anti-cancer effects as high as its root, which has commonly been used as medicine. There should be more in-depth research on the aerial part of P. japonicum in the future.

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The Effect of the Hydrogen Bond Network in the $S_1$-pocket on Catalytic Activity of Serine Protease, Achromobacter Protease I (API)

  • Lim, Seong-Il;Byun, Myung-Woo;Choi, Cheong
    • Journal of Microbiology and Biotechnology
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    • v.8 no.2
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    • pp.158-164
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    • 1998
  • Crystal structural analyses of the API-TLCK complex revealed that the ${\epsilon}$-amino group (NZ) of the lysyl part of TLCK forms hydrogen bonds with OD1 of $Asp^225$ which is a substrate specificity determinant of API, OG of $Ser^214$, O of $Ser^214$, OG1 of $Thr^189$, and O of $Thr^189$ l89/. The ${\beta}$-carboxyl oxygen of $Asp^225$ forms hydrogen bonds with the NE1 of $Trp^182$. From these observations, it is thought that besides $Asp^225$, $Thr^189$, $Ser^214$, and $Trp^182$ may also contribute to the steric specificity for lysine and high proteolytic activity of API. The side-chain hydroxyl groups of $Thr^189$ and $Ser^214$ were removed to elucidate the role of these hydrogen bonds in the $S_1$-pocket. The $k_{cat}$/$K_m$ of T189V, S214A, and T189V.S214A were decreased to 1/4, 1/3, and 1/46, respectively, of the value for native API. The decreased activities were mainly due to the increase of $K_m$. The CD and fluoroscence spectra of the three mutants were similar to those of wild-type API. With regards to the kinetic parameters ($K_i\;and\;k_2$) of mutants for the reaction involving TLCK and DFP, $k_2$decreased by increase of $K_1$ only. These results suggest that the decreased catalytic activity of these mutants is caused by the partial loss of the hydrogen bond network in the $S_1$-pocket. On the other hand, the similarity of enzymatic properties between W182F and the native enzyme suggests that the hydrogen bond between OD2 of $Asp^225$ and NE1 of $Trp^182$ is not directly related to the reaction of $Asp^225$ with the substrate.

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A Study on the Sewage Sludge and Casting Charateristic Variation During the Continus Vermicomposting (지렁이 퇴비화장치 연속운영시 하수슬러지 침출액 및 분변토 특성변화에 관한 연구)

  • Lee, Chang-Ho;Kim, Jong-Oh
    • Journal of the Korea Organic Resources Recycling Association
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    • v.11 no.3
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    • pp.35-41
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    • 2003
  • The on-site sewage sludge vermicomposting equipment was designed and evaluated on the batch and continuous tests. The vermicomposting equipment was designed to consider the mechanization as well as automation. Especially, the automatic controls of water content and temperature and the mechanization of the sludge feeding and cast separating were the important factors. In terms of changes in chemical characteristics when the equipments for experiments are operated continuously, the ORP, EC, $NH_3-N$ and $NO_3-N$ were found to be higher before and after treatment. In addition, it was found that changes in properties were low. Furthermore, the $NO_3-N$ concentration of the humus produced after treatment was found to be higher than the $NH_3-N$ concentration showing that it was appropriate based on the recycling criteria.

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Characteristics of Water Quality in Upper Stream Watershed of Dongjin River (동진강 상류하천 유역의 수질특성)

  • Son, Jae-Gwon;Park, Jong-Min;Choi, Jin-Kyu;Song, Jae-Do
    • Journal of Korean Society of Rural Planning
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    • v.9 no.2 s.19
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    • pp.19-28
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    • 2003
  • It is the purpose of this study to investigate the change of stream water quality in upper stream of Dongjin river, and to give the basic information for the conservation of water quality. Water samples were taken periodically at 9 sampling sites during 8 months from March to October in 2002. The results of this study were as follows : 1. The water temperature and pH of stream water were ranged $9.0{\sim}29.4^{\circ}C,\;6.48{\sim}9.33$, respectively. The COD values of stream water was ranged from 0.60 to 19.06. The contents of T-N and T-P mainly affected by the livestock wastes, and agricultural activity were $1.88{\sim}6.74\;mg/L$, ND(not deleted)${\sim}0.50\;mg/L$, respectively. 2. The SS, DO and BOD values of stream water were ranged $0.4mg/L{\sim}274.0mg/L$, $0.5{\sim}6.0\;mg/L$, and $7.3{\sim}13.7\;mg/L$ respectively. 3. The cation is one of the important components in analysis of stream water quality. The contents of analysis, $Ca^{++},\;Mg^{++},\;Na^+$ and $K^+$ were ranged $1.96{\sim}11.08\;mg/L$, $1.21{\sim}6.16\;mg/L$, $3.38{\sim}18.44\;mg/L$, $1.12{\sim}7.96\;mg/L$, respectively. SAR was ranged $0.31{\sim}1.63$ below 2.0. The contents of cation showed in the order $Na^{++}>Ca^{++}>K^+>Mg^+$. 4. The contents of heavy metal Zn, Cu, and Pb were $ND{\sim}0.071\;mg/L$, $ND{\sim}0.012\;mg/L$, and $ND{\sim}0.043\;mg/L$, respectively. Cd was not detected in all samples. 5. As a result of these researches showed water quality in upper stream watershed of Dongjin river more affected by livestock wastes and living sewage than agricultural activity.

Tributyltin Induces Adipogenesis and Apoptosis of Rat Thymic Epithelial Cells (Tributyltin에 의한 흰쥐 흉선 내 상피세포의 지방세포 유도와 세포자연사 증가)

  • Lee, Hyo-Jin;Lee, A-Ra;Ahn, Bo-Ram;Jeon, Eun-Je;Jeong, Ye-Ji;Yang, Hyun-Won
    • Development and Reproduction
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    • v.15 no.4
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    • pp.373-383
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    • 2011
  • Tributyltin (TBT) is one of endocrine disrupters which are known as having similar function to sex steroid hormone inducing apoptosis in various tissues of rodents. Recently, it has been reported that TBT induces apoptosis in thymus causing the decreased thymic function, but little is known about the mechanism. To elucidate the mechanism, three-week-old SD female rats were orally administrated with TBT 1, 10, and 25 mg per body weight (kg) and sesame oil as a control for 7 days. On day 8, the thymi were obtained and weighed, and then the number of thymocytes was counted. We also performed H&E staining, TUNEL assay, and Annexin V flow cytometric analysis to examine the apoptosis rates and the structure in the thymus. Next, we investigated the adipogenesis and apoptosis-related mRNA expression levels in the thymi by real-time PCR. The thymic weight and the number of thymocytes were decreased by TBT in a dose-dependent manner. As a result of the H&E staining, the boundary between cortical and medullary area was blurred in the thymi of TBT treated rats compared to those of controls. In the results of TUNEL assay and Annexin V flow cytometric analysis, apoptosis rates in the thymus were increased after TBT treatment. The expression levels of thymic epithelial cell marker genes such as EVA, KGF, AIRE, and IL-7 were significantly decreased in the thymi of TBT treated rats, but $PPAR{\gamma}$, aP2, PEPCK, and CD36 were significantly increased. The expression of $TNF{\alpha}$ and TNFR1 as apoptosis-related genes also was significantly increased after TBT treatment. The present study demonstrates that TBT can increase the expression of adipogenesis and apoptosis-related genes leading to apoptosis in the thymus. These results suggest that the increased adipogenesis of thymus by TBT exposure might induce apoptosis in the thymus resulting in a loss in thymic immune function.

Biological Toxicity Assessment of Sediment at an Ocean Dumping Site in Korea (폐기물 배출해역 퇴적물의 생물학적 독성평가 연구)

  • Seok, Hyeong Ju;Kim, Young Ryun;Kim, Tae Won;Hwang, Choul-Hee;Son, Min Ho;Choi, Ki-young;Kim, Chang-joon
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.28 no.1
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    • pp.1-9
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    • 2022
  • The effect of sediments in a waste dumping area on marine organisms was evaluated using sediment toxicity tests with a benthic amphipod (Monocorophium acherusicum) and bioluminescent bacterium (Vibrio fischeri) in accordance with the Korean Standard Method for Marine Wastes (KSMMW). Nine sites in the East Sea-Byeong, East Sea-Jeong, and Yellow Sea-Byeong areas were sampled from 2016 to 2019. The test results showed that the relative average survival rate (benthic amphipods) and relative luminescence inhibition rate (luminescent bacteria) were below 30%, which were judged to be "non-toxic." However, in the t-test, a total of 12 benthic amphipod samples (6, 1, 1, and 4 in 2016, 2017, 2018, and 2019, respectively) were significantly different (p<0.05) from the control samples. To identify the source of toxicity on benthic amphipods, a simple linear regression analysis was performed between the levels of eight heavy metals (Cr, As, Ni, Cd, Cu, Pb, Zn, and Hg) in sediments and the relative average survival rate. The results indicated that Cr had the highest contribution to the toxicity of benthic amphipods (p = 0.000, R2 = 0.355). In addition, Cr was detected at the highest concentration at the DB-85 station and exceeded the Marine Environment Standards every year. Although the sediments were determined as "not toxic" according to the ecotoxicity criteria of the KSMMW, the results of the statistical significance tests and toxicity identification evaluation indicated that the toxic effect was not acceptable. Therefore, revising the criteria for determining the toxic effect by deriving a reference value through quantitative risk assessment using species sensitivity distribution curves is necessary in the future.

Size Distributions of Trace Elements in Airborn Particulates Collected using Drum impactor at Gosan, Jeju Island : Measurements in Springtime 2002 (DRUM impactor를 이용한 대기 입자상 물질 중 원소성분의 입경분포 특성 : 제주도 고산지역의 2002년 봄철 (3.29-5.30) 측정 연구)

  • 한진석;문광주;류성윤;안준영;공부주;홍유덕;김영준
    • Journal of Korean Society for Atmospheric Environment
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    • v.20 no.4
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    • pp.555-569
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    • 2004
  • Size -segregated measurements of aerosol composition using 8-stage DRUM impactor are used to determine the transport of natural and anthropogenic aerosols at Gosan site from 29 March to 30 May in 2002. Separation of ambient aerosols by DRUM impactor offers many Advantages over other standard filtration techniques. Some of the most important advantages are the ability to segregate into details by particle tire, to better preserve chemical integrity since the air stream doesn't pars through the deposit, to collect samples as a function of time, and to have a wide variety of impaction surfaces available to match analytical needs. Although the transport of Yellow sand is a well-known phenomenon in springtime, the result of measurement shows that not only soil dust but also anthropogenic aerosols, including sulfur, enriched trace metals such as Pb, Ni, Zn. Cu, Cr, As, Se, Br, are transported to Gosan in springtime. This study combines the size- and time-resolved aerosol composition measurements with isentropic, backward air-mass trajectories in order to identify some potential source regions of anthropogenic aerosols. As a result, during the NYS period, the average concentration of PM$_{10}$ was 46$\mu\textrm{g}$/㎥, Si, Al. S, Fe, Cl, K, Ca were higher than 1,000 ng/㎥ and Ti was about 100 ng/㎥. The concentrations of Zn, Mn, Cu. Pb, Br, Rb, V, Cr, Ni. At, Se ranged between 1 and 70 ng/㎥. More than 50% typical soil elements, tuck as Al, Si, Fe, Cd. Ti, Cr, Cu, Br. were distributed in a coarse particle range(5.0-12${\mu}{\textrm}{m}$). In other hand, anthropogenic pollutants, luck as S, N, Vi, were mainly distributed in a fine particle range (0.09-0.56${\mu}{\textrm}{m}$). During the YS period, PM$_{10}$ increased about 8 times than NYS period, and main soil elements, such as Al, Si, S, K, V, Mn, Fe also doubled in coarse particle range (1.15-12${\mu}{\textrm}{m}$). But Zn, As, Pb, Cu and Se, which distributed in the time aerosols (0.09-0.56${\mu}{\textrm}{m}$), were on the same level with or decreased than NYS period. Finally. except the YS Period, coarse particles (2.5-12${\mu}{\textrm}{m}$) are inferred to be influenced by soil, coal combustion, waste incineration, ferrous and nonferrous sources through similar pathways with Yellow Sand. But fine particles have different sources, such as coal combustion, gasoline vehicle, biomass burning, oil or coal combustion, nonferrous and ferrous metal sources, which are transported from China, Korea peninsula and local sources.ces.