• 제목/요약/키워드: critical pathway

Search Result 430, Processing Time 0.024 seconds

Iron chelating agent, deferoxamine, induced apoptosis in Saos-2 osteosarcoma cancer cells (Saos-2 골육종 세포에서 iron chelating agent, deferoxamine에 의한 apoptosis 유도)

  • Park, Eun Hye;Lee, Hyo Jung;Lee, Soo Yeon;Kim, Sun Young;Yi, Ho Keun;Lee, Dae Yeol;Hwang, Pyoung Han
    • Clinical and Experimental Pediatrics
    • /
    • v.52 no.2
    • /
    • pp.213-219
    • /
    • 2009
  • Purpose:Iron is a critical nutritional element that is essential for a variety of important biological processes, including cell growth and differentiation, electron transfer reactions, and oxygen transport, activation, and detoxification. Iron is also required for neoplastic cell growth due to its catalytic effects on the formation of hydroxyl radicals, suppression of host defense cell activities, and promotion of cancer cell multiplication. Chronic transfusion-dependent patients receiving chemotherapy may have iron overload, which requires iron-chelating therapy. We performed this study to demonstrate whether the iron chelating agent deferoxamine induces apoptosis in Saos-2 osteosarcoma cells, and to investigate the underlying apoptotic mechanism. Methods:To analyze the apoptotic effects of an iron chelator, cultured Saos-2 cells were treated with deferoxamine. We analyzed cell survival by trypan blue and crystal violet analysis, apoptosis by nuclear condensation, DNA fragmentation, and cell cycle analysis, and the expression of apoptotic related proteins by Western immunoblot analysis. Results:Deferoxamine inhibited the growth of Saos-2 cell in a time- and dose-dependent manner. The major mechanism for growth inhibition with the deferoxamine treatment was by the induction of apoptosis, which was supported by nuclear staining, DNA fragmentation analysis, and flow cytometric analysis. Furthermore, bcl-2 expression decreased, while bax, caspase-3, caspase-9, and PARP expression increased in Saos-2 cells treated with deferoxamine. Conclusion:These results demonstrated that the iron chelating agent deferoxamine induced growth inhibition and mitochondrial-dependent apoptosis in osteosarcoma Saos-2 cells, suggesting that iron chelating agents used in controlling neoplastic cell fate can be potentially developed as an adjuvant agent enhancing the anti-tumor effect for the treatment of osteosarcoma.

The Characteristics Asian Dust Observed in Japan Deflecting the Korean Peninsula (2010. 5. 22.-5. 25.) (한반도를 돌아 일본에서 관측된 황사의 특징 (2010년 5월 22일-5월 25일))

  • Ahn, Bo-Young;Chun, Young-Sin
    • Journal of the Korean earth science society
    • /
    • v.32 no.4
    • /
    • pp.388-401
    • /
    • 2011
  • Asian dust was observed a total of 66 times in the springtime during the period from 2002 to 2010, with 26 cases in March, 23 cases in April and 17 cases in May. This study investigates a Asian dust episode that occurred during the period from 22 to 25 May 2010, based on synoptic weather patterns, wind vector at 850 hPa, relative humidity at 1000 hPa, Jet streams and wind vector at 300 hPa, PM10 concentration in Korea and satellite imagery. In this case, Asian dust originated on 22 May along the rear of a developing low pressure system in Mongolia. The Asian dust was then transported southeastward and bypassed the Korea peninsula from 23 to 24 May, before reaching Japan on 25 May. Jet streams on 24 May bypassed the Korean peninsula and induced the development of a surface low pressure centered over the peninsula. The resulting air flow was critical to the trajectory of the Asian dust, which likewise bypassed the Korean peninsula. 72-hour backward trajectory data reveal that the Shandong Peninsula and the East China Sea were the points of origin for the air flows that swept through the Japanese sites where Asian dust was observable to the naked eay. The Asian dust pathway is ascertained by horizontal distribution of the Asian dust of RGB imagery from MODIS satellites which captured the Asian dust moving over the Shandong Peninsula, the East China Sea, and northwest of the Kyushu region in Japan. Since the synoptic pattern and the transport way of the Asian dust case are far from typical ones, which Asian dust forecasting technique has long been based on, this study can be good example of exceptional Asian dust pattern and it will be used for more accurate Asian dust forecasting.

Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells

  • Xiong, Wei;Jiang, Yong-Xin;Ai, Yi-Qin;Liu, Shan;Wu, Xing-Rao;Cui, Jian-Guo;Qin, Ji-Yong;Liu, Yan;Xia, Yao-Xiong;Ju, Yun-He;He, Wen-Jie;Wang, Yong;Li, Yun-Fen;Hou, Yu;Wang, Li;Li, Wen-Hui
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.8
    • /
    • pp.3395-3402
    • /
    • 2015
  • Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

PGE2 Mediated INF-γ Gene Methylation Through cAMP Signaling Pathway in Human Jurkat T Cells (인간의 Jurkat T세포에서 프로스타글란딘 PGE2) (PGE2)의 cAMP 경로를 통한 인터페론 감마(INF--γ ) 유전자의 methylation)

  • Jeon, Byung-Hun;Ju, Sung-Min;Jeong, Jae-Sung;Kim, Myung-Wan;Yun, Young-Gab;Park, Hyun;Chung Hun-taeg;Han, Dong-Min;Kim, Won-Sin
    • Journal of Life Science
    • /
    • v.14 no.4
    • /
    • pp.670-675
    • /
    • 2004
  • We have examined the effects of S-nitroso-N-acetylpenicillamine (SNAP), prostaglandin $E_2$ (PG $E_2$) and dibutric cyclic AMP (dbcAMP) on the methylation of interferon- ${\gamma}$ (IFN- ${\gamma}$ ) gene in human Jurkat T cells. The CpG dinucleotide which is critical for promoter function of IFN- ${\gamma}$ gene was methylated by treatment with SNAP, PG $E_2$ and dbcAMP, respectively. The DNA methylation induced by PG $E_2$ was suppressed by the addition of 2',5'-dideoxyadenosine (DDA), an inhibitor of adenylyl cyclase, but the suppression was not observed in SNAP treated cells. The NO production was not enhanced in PG $E_2$ or dbcAMP treated cells. The methylation induced by PG $E_2$ and dbcAMP was not suppressed by the addition of $N^{G}$-methyl-L-arginine (L-NMMA), NO synthase inhibitor. In conclusion, the inhibition of INF- ${\gamma}$ gene expression by PG $E_2$ was associated with the methylation of INF- ${\gamma}$ gene by elevation of intracellular cAMP in human Jurkat T cells. However, the methylation induced by PG $E_2$ might not be mediated through the NO production.rough the NO production.

Neuroprotective effects of Extract of Broccoli, Cultivated in Desalinated Magma Seawater, on neuron-like SH-SY5Y cells (제주도 탈염 용암해수 재배로 제조한 브로콜리 추출물의 신경 세포 보호 효과)

  • Rhee, Jin Seol;Jang, Youn Bi;Choi, Ge Sun;Choung, Jai Jun;Kang, Seung Woo
    • Journal of the Korean Applied Science and Technology
    • /
    • v.37 no.3
    • /
    • pp.448-462
    • /
    • 2020
  • Dietary nutrition is a critical lifestyle factor that can reduce the risk of future cognitive impairments caused by dementia. Accumulating evidence suggests that dietary supplementation with Sulforaphane may help the prevention of cognitive impairments and dementia. Thus, Sulforaphane-enriched broccoli extract would hold promise to improve cognitive impairments of dementia patients. Here, we have used broccoli extracts, prepared from broccoli cultivated in Magma Seawater, to test if the broccoli extracts can be dietary supplement to improve cognitive impairments. Magma Seawater originated from Jeju Island, Korea is unique in terms of containing high concentrations of usable minerals (Zinc, Vanadium and Germanium etc.). Broccoli, grown in Magma Seawater, would contain Sulforaphane and the extra amount of usable minerals. The chemical compositions of the broccoli extracts were analyzed using LC-Q-orbitrap to detect Sulforaphane and Glucoraphanin. Analysis method based on HPLC was developed for measurement of sulforaphane levels in the broccoli extracts. We have tested if the broccoli extracts have anti-apoptotic and anti-inflammatory effects on neuron-like SH-SY5Y cells. In addition, we examined if the broccoli extracts are able to upregulate expression of synaptic plasticity-associated proteins (BDNF and phospho-CREB) and to inhibit acetylcholine esterase (AchE) activity. We have shown that the broccoli extracts inhibited the apoptotic pathway and inflammatory responses. Finally, we present evidence showing that AchE activity was inhibited by the broccoli extracts, but expression of BDNF and phospho-CREB was upregulated. Taken together, these findings suggest that the broccoli extracts from Magma Seawater-grown broccoli would be a good source of dietary nutrition to improve cognitive impairments in the future.

The expression patterns of RANKL and OPG in murine tooth eruption (치아발육시기에서의 RANKL 및 OPG의 발현 양상)

  • Hwang, Kyung-Mun;Kim, Eun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun;Kim, Hyun-Jung
    • Journal of the korean academy of Pediatric Dentistry
    • /
    • v.33 no.2
    • /
    • pp.290-303
    • /
    • 2006
  • Tooth eruption is a complex and tightly regulated process that involves cells of the tooth organ and the surrounding alveolus. Osteoclast precursors must be recruited into the dental follicle prior to the onset of eruption. This function of dental follicle may be regarded as the ability of bone remodeling characterized by the interaction of osteoclasts and osteoblasts. This is because tooth eruption is a localized event in which many of the genes required for eruption are expressed in the dental follicle. RANKL is a membrane-bound protein that is a member of the TNF ligand family. which is present on bone marrow stromal cells and osteoblasts, and induces osteoclast formation and activation from precursor cell. The biologic effect of RANKL is inhibited by OPG and, in bone, the relative ratio of RANKL and OPG modulates osteoclastogenesis. To evaluate the roles of RANKL and OPG in tooth eruption and the relations with the expression pattern of Runx2, in situ hybridization was performed with mandibles of mice at postnatal stage 1, 3, 5, 7, 9 and 11. mRNA of RANKL, OPG, and Runx2 are expressed in dental follicle and surrounding tissue from P1 to 11. To determine the sites of osteoclastic activity during tooth eruption, mandibles were dissected. Peak osteoclastic activity in alveolar bone along the occlusal and basal regions was observed from P5 to 9, with osteoclasts in these regions being large and strongly TRAP-positive The specific spatio-temporal expression patterns of RANKL, OPG, and Runx2 in our study suggest that tooth eruption could be progressed through the interactions of molecular signaling among dental follicle, dental organ and alveolar bone, furthermore it means that dental follicle is quite important in tooth eruption In addition, it indicates that these genes (RANKL, OPG, and Runx2) play critical roles in tooth eruption.

  • PDF

Mechanisms of Lipopolysaccharide-induced Lipopolysaccharide Tolerance in the Expression of TNF-$\alpha$ and IL-8 in Peripheral Blood Monocytes (말초 혈액 단핵구의 TNF-$\alpha$와 IL-8 발현에서 내독소에 대한 내성 기전에 관한 연구)

  • Park, Gye-Young;Kim, Jae-Yeol;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
    • /
    • v.44 no.3
    • /
    • pp.601-610
    • /
    • 1997
  • Background : Monocytes/macrophages play a central role in determining the host response during Gram-negative infection through secretion of a variety of mediators after stimulation of LPS. Even though cytokine production has been shown to play an important role in host defense during sepsis, cytokine release may also lead to tissue injury. Thus, regulation of macrophage response to LPS is critical for host survival during Gram-negative sepsis. In animals exposed to nonlethal doses of endotoxin, a characteristic hyporesponsiveness to subsequent administration of endotoxin has been observed. This phenomenon was known as 'LPS tolerance'. However, little information is available regarding the underlying mechanism of LPS tolerance. Method : Peripheral blood monocyte(PBMC) was isolated from peripheral blood of normal volunteers by adhesion purification method. To evaluate the conditions to obtain LPS tolerance, preculture was carried out with LPS at 10ng/ml for 24 hours. For stimulation, culture plates were washed two times and were stimulated with LPS at $1{\mu}g/ml$ for 4, 6 and 26 hours. To assess the underlying mechanisms of LPS tolerance, autologous serum, PMA, anti-CD14 Ab, Indomethacin or $PGF_2$ were added to preculture solution respectively. Cytokine concentrations in culture supernatants were measured using ELISA for TNF-$\alpha$ and IL-8 and mRNA of TNF-$\alpha$ and IL-8 were determined by Northern blot analysis. Results : The exposure of PBMC to low dose of LPS suppressed the cytokine production and mRNA expression of TNF-$\alpha$, but not IL-8. Anti-CD14 Ab partially recovered production of TNF-$\alpha$ which was suppressed by preculture with low dose LPS. The preculture with PMA induces LPS tolerance, as preculture with low dose LPS. Conclusion : LPS tolerance to TNF-$\alpha$ is regulated pretranslationally and is influenced by protein kinase C pathway and CD14.

  • PDF

Responses of Soybean Yield to High Temperature Stress during Growing Season: A Case Study of the Korean Soybean (재배기간 동안 이상고온 발생에 따른 콩의 수량반응 탐색)

  • Chung, Uran;Cho, Hyeoun-Suk;Kim, Jun-Hwan;Sang, Wan-Gyu;Shin, Pyeong;Seo, Myung-Chul;Jung, Woo-Seuk
    • Korean Journal of Agricultural and Forest Meteorology
    • /
    • v.18 no.4
    • /
    • pp.188-198
    • /
    • 2016
  • In soybeans, responses of high temperature according to shift of sowing dates during the growing season was explored using the crop model, CROPGRO-soybean. In addition, it analyzed impact on change of sowing dates affects yield potential of soybean under future climate scenario (2041-2070). In Jeonju and Miryang during 1981-2010, if sowing at 15 or ten days ahead from 10 June, namely in shorten of the sowing day (i.e. when sown on 25 or 30 May), the yield potential reduced. However, the yield potential increased when sown 5 June. In the case of delay of sowing day (i.e. when sown on 15 or 20 June), reduction of yield potential in the average -5% was higher than increase in the average +2%. In particular, the relative changes for shorten of the sowing day or delay of the sowing day do not be shown in normal years which high temperatures did not abnormally occur during the growing season from 2003 to 2010 except when sown on 25 May. In abnormal years which high temperatures occurred during the critical period, especially R5 to R7, shorten of the sowing day affected to the increase of yield potential in Miryang, while the yield potential decreased in Jeonju except when sown on 5 June. However, delay of the sowing day influenced on the reduction of yield potential both in two sites. In future climate scenario of Representative Concentration Pathway (RCP) 8.5 during from 2041 to 2070, the increase and decrease of yield potential for shorten of the sowing day were +10/-9% for RCP 8.5 of Jeonju, and +14/-9% for RCP 8.5 of Miryang, respectively. Additionally, it showed +10/-17% for RCP 8.5 in Jeonju, and +10/-29% for RCP 8.5 in Miryang, respectively in the increase and decrease of yield potential for delay of the sowing day.

Expressions of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-2 with Changes of Interleukin-6 and Interleukin-18 in Atherosclerotic Lesions of Hypercholesterolemic Rabbits (고콜레스테롤혈증 가토의 죽상경화성 병변에서 Interleukin-6와 Interleukin-18의 변화 및 Matrix Metalloproteinase-9과 Tissue Inhibitor of Metalloproteinase-2의 발현)

  • 권영무;김성숙;장봉현
    • Journal of Chest Surgery
    • /
    • v.35 no.6
    • /
    • pp.407-419
    • /
    • 2002
  • Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by progressive accumulation of lipids, cells, and extracellular matrix. Matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases(TIMPS) contribute to vascular matrix remodeling in atherosclerosis, and some cytokines may play role in the synthesis or activation of MMPs or TIMPs. Material and Method: We produced experimental atherosclerotic plaques in 9 rabbits by atherogenic hypercholesterol diet for 12 weeks, and 10 other rabbits were used as control group with standard laboratory chow, At that time, 19 rabbits were sacrificed and aorta, coronary arteries and blood specimens were prepared. The expressions of MMP-9, TIMP-2 and interleukin(IL)-18, and the bioactivity of IL-6 were investigated with H&E stain, immunohistochemical stain, immunoblotting(Western blot analysis), and bioassay. Result: Serum cholesterol in the experimental group increased up to 1258$\pm$262 mg/dL(control group: 41$\pm$7 mg/dL). All experimental group showed well-developed atherosclerotic plaques in aorta and coronary artery. The expression of MMP-9 in aorta and coronary artery of the experimental group showed significant increase than that of the control group by immunohistochemistry. Among the experimental group, complicated lesions with intimal rupture or complete luminal occlusion, demonstrated stronger expression of MMP-9. Interestingly, there was no difference in expression of TIMP-2 between the experimental and the control group. These findings were confirmed by Western blot analysis. The bioassay revealed significant up-regulation of serum bioactivity of IL-6 in the experimental group(4819.60$\pm$2021.25 IU/$m\ell$) compared to that of IL-6 in the control group(27.20 $\pm$ 12.19 IU/$m\ell$). IL-18 was expressed in all atherosclerotic plaques, whereas little or no expression was detected in the control group. Conclusion: The increased MMP-9 expression along with the unchanged TIMP-2 expression seem to be contributory factors in extracellular matrix degradation in atherosclerosis. Focal overexpression of MMP-9 may promote plaque destabilization and cause complications of atherosclerotic plaques such as thrombosis with/without acute coronary syndrome. Elevation of IL-6 and IL-18 may be more than just markers of atherosclerosis but actual participants in lesion development. Identification of critical regulatory pathway is important to improve the understanding of the cellular and molecular basis of atherosclerosis and may open the way for novel therapeutic strategies.

Risk Assessment of As, Cd, Cu and Pb in Different Rice Varieties Grown on the Contaminated Paddy Soil (중금속 오염 논토양에서 재배된 벼 품종간 위해성평가 비교)

  • Kim, Won-Il;Kim, Jin-Kyoung;Yoo, Ji-Hyock;Paik, Min-Kyoung;Park, Sang-Won;Kwon, Oh-Kyung;Hong, Moo-Ki;Yang, Jay-E;Kim, Jeong-Gyu
    • Korean Journal of Soil Science and Fertilizer
    • /
    • v.42 no.1
    • /
    • pp.53-57
    • /
    • 2009
  • Heavy metal pollution may be one of the most serious challenges confront crop production and human health. Therefore, the selection of heavy metal tolerance cultivars which adapted to the contaminated fields will introduced a suitable solution for management this critical environmental risk. The objectives of this research is to assess human health risk using geochemical analyses and exposure assessment of heavy metals in rice cultivars. Risk for inhabitants in the closed mine area was comparatively assessed for As, Cd, Cu and Pb in 10 rice varieties as a major exposure pathway. The average daily dose (ADD) of each heavy metal was estimated by analyzing the exposure pathways to rice and soil. For the non-carcinogenic risk characterization, Hazard Quotient (HQ) and Hazard Index (HI) were calculated using toxicity indices provided by US-EPA IRIS. The different rice varieties revealed a wide range of HI values from 23.6 to 34.3, indicating that all rice varieties have a high potential toxic risk. The DA rice variety showed the lowest HI value while the TB rice variety the highest. The probabilities of cancer risk for As via rice consumption were varied with rice varieties ranging from 2.0E-03 to 3.5E-03 which exceeded the regulatory acceptable risk of 1 in 10,000 set by US-EPA. The DA rice variety also showed the lowest value while the TB rice variety gave the highest value. Our results indicate that risk assessment can be contribute to screen the pollution safe rice cultivars in paddy fields affected by the mining activity.