• Title/Summary/Keyword: Human Response Model

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Genetic Variations in the HIF1A Gene Modulate Response to Adjuvant Chemotherapy after Surgery in Patients with Colorectal Cancer

  • Zhang, Yi;Wang, Peng;Zhou, Xing-Chun;Bao, Guo-Qiang;Lyu, Zhuo-Ming;Liu, Xiao-Nan;Wan, Shao-Gui;He, Xian-Li;Huang, Qi-Chao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4637-4642
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    • 2014
  • Background: Hypoxia-inducible factor $1{\alpha}$ (HIF-$1{\alpha}$) plays an important role in regulating cell survival and angiogenesis, which are critical for tumor growth and metastasis. Genetic variations of HIF1A have been shown to influence the susceptibility to many kinds of human tumors. Increased expression of HIF-$1{\alpha}$ has also been demonstrated to be involved in tumor progression. However, the prognostic value of single nucleotide polymorphisms (SNPs) inthe HIF1A gene remains to be determined in most cancer types, including colorectal cancer (CRC). In this study, we sought to investigate the predictive role of HIF1A SNPs in prognosis of CRC patients and efficacy of chemotherapy. Materials and Methods: We genotyped two functional SNPs in HIF1A gene using the Sequenom iPLEX genotyping system and then assessed their associations with clinicopathological parameters and clinical outcomes of 697 CRC patients receiving radical surgery using Cox logistic regression model and Kaplan Meier curves. Results: Generally, no significant association was found between these 2 SNPs and clinical outcomes of CRC. In stratified analysis of subgroup without adjuvant chemotherapy, patients carrying CT/TT genotypes of rs2057482 exhibited a borderline significant association with better overall survival when compared with those carrying CC genotype [Hazard ratio (HR), 0.47; 95% confidence interval (95% CI): 0.29-0.76; P < 0.01]. Moreover, significant protective effects on CRC outcomes conferred by adjuvant chemotherapy were exclusively observed in patients carrying CC genotype of rs2057482 and in those carrying AC/CC genotype of rs2301113. Conclusions: Genetic variations in HIF1A gene may modulate the efficacy of adjuvant chemotherapy after surgery in CRC patients.

A Comparative Study on the Logic Structure of Myeongri Old Law and New Law (명리학 고법과 신법의 논리구조 비교연구)

  • Na, Hyeok-Jin;Jung, Kyeong-Hwa
    • Industry Promotion Research
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    • v.5 no.3
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    • pp.61-71
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    • 2020
  • The purpose of this paper is to reaffirm the logical framework of the saju analysis method by recreating the saju model of old-law to study and organize the theories of frame in old-law Myeongri, and then by organizing and comparing the logic structure of the saju analysis method of new-law and old-law. Some believe that Myeongri Theory first appeared in the world in the Warring States Period when they were active with Gwigokja and Naknokja as origin, while others believe that it was origin that "Okjokyeong" was written by Kwak-Bak of Eastern Jin after a while. Since then, Myeongri Theory, which had been organized by Won-Cheongang and Yi-Heojung, has undergone a major transformation since reaching the Song Dynasty Seo-Japyeong. Based on this point, the Myeongri Theory of the previous generation is called the Old-law, and the subsequent theory is called the New-law. The changes in the logic structure of the old-law and the new-law leave a big difference and disconnect between those. But comparative studies have confirmed that the philosophy and logic structure due to natural laws that have not changed much such as the symbolic system of nature called Yinyang & five elements and Cheongan-jiji, the idea of a heavenly response projected in the Three Wonders of heaven, earth and human, and the concept of generation and time in the position of year-month-day-time.

Optimum Enzyme Mixture of Cellulase, Hemicellulase, and Xylanase for Production of Water-Soluble Carbohydrates from Rice Straw (볏짚 유래 수용성 탄수화물 생산에 있어 cellulase, hemicellulase 및 xylanase 최적혼합조건)

  • Cho, Sang-Buem;Lee, Sang-Suk;Kim, Chang-Hyun;Ryu, Kyeong-Seon;Park, Hee-Jun;Myong, Hyun;Choi, Nag-Jin
    • Journal of Life Science
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    • v.22 no.1
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    • pp.74-79
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    • 2012
  • This study was conducted to investigate the production of water-soluble carbohydrates (WSCs) by treatment of different amounts of rice straw with cellulase, hemicellulase, and xylanase. Treatment of high amounts of rice straw (100 g/l) with cellulase and hemicellulase resulted in similar production of WSCs. Reducing the amount of rice straw to 50 g/l decreased the production of WSCs by hemicellulase but had no effect on WSC production by cellulase. The interaction among rice straw amounts, and hemicellulase and xylanase activities was investigated using a Box Behnken design and a response surface model. An interaction was found only between hemicellulase and xylanase. An enzyme mixture consisting of 0.55 mg/ml of hemicellulase and 0.65 mg/ml of xylanase generated the highest amounts of WSCs, regardless of the amount of rice straw provided. Therefore, the activity of cellulase was higher than that of either hemicellulose or xylanase for WSC production from rice straw. The interaction observed for hemicellulase and xylanase indicates that a combined enzyme treatment could improve the production of WSCs from rice straw.

Relationship between Radiation Induced Activation of DNA Repair Genes and Radiation Induced Apoptosis in Human Cell Line A431 (인체세포주 A431에서 방사선 조사 후 DNA수선 유전자 발현과 세포고사와의 관계에 관한 연구)

  • Bom, Hee-Seung;Min, Jung-Jun;Choi, Keun-Hee;Kim, Kyung-Keun
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.2
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    • pp.144-153
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    • 2000
  • Purpose: The purpose of this study was to evaluate the relationship between radiation-induced activation of DNA repair genes and radiation induced apoptosis in A431 cell line. Materials and Methods: Five and 25 Gys of gamma radiation were given to A431 cells by a Cs-137 cell irradiator. Apoptosis was evaluated by flow cytometry using annexin V-fluorescein isothiocyanate and propidium iodide staining. The expression of DNA repair genes was evaluated by both Northern and Western blot analyses. Results: The number of apoptotic cells increased with the increased radiation dose. It increased most significantly at 12 hours after irradiation. Expression of p53, p21, and hRAD50 reached the highest level at 12 hours after 5 Gy irradiation. In response to 25 Gy irradiation, hRAD50 and p21 were expressed maximally at 12 hours, but p53 and GADD45 genes showed the highest expression level after 12 hours. Conclusion: Induction of apoptosis and DNA repair by ionizing radiation were closely correlated. The peak time of inducing apoptosis and DNA repair was 12 hours in this study model. hRAD50, a recently discovered DNA repair gene, was also associated with radiation-induced apoptosis.

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Protective Effect of Wheat Bran Extract against β-Amyloid-induced Cell Death and Memory Impairment (베타아밀로이드로 유도된 신경세포 사멸과 기억력 손상에 대한 밀기울추출물의 보호효과)

  • Lee, Chan;Park, Gyu-Hwan;Lee, Jong-Won;Jang, Jung-Hee
    • The Korea Journal of Herbology
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    • v.30 no.1
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    • pp.67-75
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    • 2015
  • Objectives : The aim of this study is to examine the neuroprotective effect of wheat bran extract (WBE) against ${\beta}$-amyloid ($A{\beta}$)-induced apoptotic cell death in SH-SY5Y human neuroblastoma cells and memory impairment in triple transgenic animal model's of Alzheimer's disease (3xTg AD mice). Methods : In SH-SY5Y cells, MTT assay and TUNEL staining were conducted to evaluate the protective effect of WBE against $A{\beta}_{25-35}$-induced neurotoxicity and apoptosis. Alterations in mitochondrial transmembrane potential (MMP), expression of proapoptotic Bax and antiapoptotic Bcl-2 proteins, cleavage of PARP, and brain-derived neurotrophic factor (BDNF) levels were analyzed to elucidate the neuroprotective mechanism of WBE. To further investigate the memory enhancing effect of WBE, Morris water maze test was performed in 3xTg AD mice. Results : In SH-SY5Y cells, WBE protected against $A{\beta}_{25-35}$-caused cytotoxicity and apoptosis as shown by the restoration of cell viability in MTT assay and inhibition of DNA fragmentation in TUNEL staining. $A{\beta}_{25-35}$-induced apoptotic signals such as dissipation of MMP, decreased Bcl-2/Bax ratio, and cleavage of PARP were suppressed by WBE. Moreover, WBE up-regulated the protein levels of BDNF, which seemed to be mediated by activation of cAMP response element-binding protein (CREB). In 3xTg AD mice, oral administration of WBE attenuated learning and memory deficit as verified by reduced mean escape latency in water maze test. Conclusions : WBE protects neuronal cells from $A{\beta}_{25-35}$-induced apoptotic cell death and restores learning and memory impairments in 3xTg AD mice. These findings suggest that WBE exhibit neuroprotective potential for the management of AD.

In-depth Review of IPCC 5th Assessment Report (IPCC 제5차 과학평가보고서 고찰)

  • Park, Il-Soo;Woon, Yu;Chung, Kyung-Won;Lee, Gangwoong;Owen, Jeffrey S.;Kwon, Won-Tae;Yun, Won-Tae
    • Journal of Korean Society for Atmospheric Environment
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    • v.30 no.2
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    • pp.188-200
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    • 2014
  • The IPCC 5th Assessment Report (Climate Change 2013: The Physical Science Basis) was accepted at the 36th Session of the IPCC on 26 September 2013 in Stockholm, Sweden. It consists of the full scientific and technical assessment undertaken by Working Group I. This comprehensive assessment of the physical aspects of climate change puts a focus on those elements that are relevant to understand past, document current, and project future of climate change. The assessment builds on the IPCC Fourth Assessment Report and the recent Special Report on Managing the Risk of Extreme Events and Disasters to Advance Climate Change Adaptation. The assessment covers the current knowledge of various processes within, and interactions among, climate system components, which determine the sensitivity and response of the system to changes in forcing, and they quantify the link between the changes in atmospheric constituents, and hence radiative forcing, and the consequent detection and attribution of climate change. Projections of changes in all climate system components are based on model simulations forced by a new set of scenarios. The report also provides a comprehensive assessment of past and future sea level change in a dedicated chapter. The primary purpose of this Technical Summary is to provide the link between the complete assessment of the multiple lines of independent evidence presented in the main report and the highly condensed summary prepared as Policy makers Summary. The Technical Summary thus serves as a starting point for those readers who seek the full information on more specific topics covered by this assessment. Warming of the climate system is unequivocal, and since the 1950s, many of the observed changes are unprecedented over decades to millennia. The atmosphere and ocean have warmed, the amounts of snow and ice have diminished, sea level has risen, and the concentrations of greenhouse gases have increased. Total radiative forcing is positive, and has led to an uptake of energy by the climate system. The largest contribution to total radiative forcing is caused by the increase in the atmospheric concentration of $CO_2$ since 1750. Human influence on the climate system is clear. This is evident from the increasing greenhouse gas concentrations in the atmosphere, positive radiative forcing, observed warming, and understanding of the climate system. Continued emissions of greenhouse gases will cause further warming and changes in all components of the climate system. Limiting climate change will require substantial and sustained reductions of greenhouse gas emissions. The in-depth review for past, present and future of climate change is carried out on the basis of the IPCC 5th Assessment Report.

Impact on Inflammation and Recovery of Skin Barrier by Nordihydroguaiaretic Acid as a Protease-Activated Receptor 2 Antagonist

  • Kim, Hyo-Young;Goo, Jung-Hyun;Joo, Yeon-Ah;Lee, Ha-Yoen;Lee, Se-Mi;Oh, Chang-Taek;Ahn, Soo-Mi;Kim, Nam-Hoon;Hwang, Jae-Sung
    • Biomolecules & Therapeutics
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    • v.20 no.5
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    • pp.463-469
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    • 2012
  • Atopic dermatitis is a chronic, inflammatory disease of the skin with increased transepidermal water loss. Both an abnormal inflammatory response and a defective skin barrier are known to be involved in the pathogenesis of atopic dermatitis. Protease activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$. PAR2 is expressed in suprabasal layers of the epidermis and regulates inflammatory responses and barrier homeostasis. In this study, we show that nordihydroguaiaretic acid (NDGA) inhibits the PAR2-mediated signal pathway and plays a role in skin barrier recovery in atopic dermatitis. Specifically, NDGA reduces the mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes by down-regulating inflammatory mediators, such as interleukin-8, thymus and activation-regulated chemokine and intercellular cell adhesion molecule-1 in HaCaT keratinocytes. Also, NDGA decreases the protein expression of involucrin, a differentiation maker of keratinocyte, in both HaCaT keratinocytes and normal human epidermal keratinocytes. We examined NDGA-recovered skin barrier in atopic dermatitis by using an oxazolone-induced atopic dermatitis model in hairless mice. Topical application of NDGA produced an increase in transepidermal water loss recovery and a decrease in serum IgE level, without weight loss. Accordingly, we suggest that NDGA acts as a PAR2 antagonist and may be a possible therapeutic agent for atopic dermatitis.

Genetic signature of strong recent positive selection at interleukin-32 gene in goat

  • Asif, Akhtar Rasool;Qadri, Sumayyah;Ijaz, Nabeel;Javed, Ruheena;Ansari, Abdur Rahman;Awais, Muhammd;Younus, Muhammad;Riaz, Hasan;Du, Xiaoyong
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.7
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    • pp.912-919
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    • 2017
  • Objective: Identification of the candidate genes that play key roles in phenotypic variations can provide new information about evolution and positive selection. Interleukin (IL)-32 is involved in many biological processes, however, its role for the immune response against various diseases in mammals is poorly understood. Therefore, the current investigation was performed for the better understanding of the molecular evolution and the positive selection of single nucleotide polymorphisms in IL-32 gene. Methods: By using fixation index ($F_{ST}$) based method, IL-32 (9375) gene was found to be outlier and under significant positive selection with the provisional combined allocation of mean heterozygosity and $F_{ST}$. Using nucleotide sequences of 11 mammalian species from National Center for Biotechnology Information database, the evolutionary selection of IL-32 gene was determined using Maximum likelihood model method, through four models (M1a, M2a, M7, and M8) in Codeml program of phylogenetic analysis by maximum liklihood. Results: IL-32 is detected under positive selection using the $F_{ST}$ simulations method. The phylogenetic tree revealed that goat IL-32 was in close resemblance with sheep IL-32. The coding nucleotide sequences were compared among 11 species and it was found that the goat IL-32 gene shared identity with sheep (96.54%), bison (91.97%), camel (58.39%), cat (56.59%), buffalo (56.50%), human (56.13%), dog (50.97%), horse (54.04%), and rabbit (53.41%) respectively. Conclusion: This study provides evidence for IL-32 gene as under significant positive selection in goat.

The activation of NLRP3 inflammasome potentiates the immunomodulatory abilities of mesenchymal stem cells in a murine colitis model

  • Ahn, Ji-Su;Seo, Yoojin;Oh, Su-Jeong;Yang, Ji Won;Shin, Ye Young;Lee, Byung-Chul;Kang, Kyung-Sun;Sung, Eui-Suk;Lee, Byung-Joo;Mohammadpour, Hemn;Hur, Jin;Shin, Tae-Hoon;Kim, Hyung-Sik
    • BMB Reports
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    • v.53 no.6
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    • pp.329-334
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    • 2020
  • Inflammasomes are cytosolic, multiprotein complexes that act at the frontline of the immune responses by recognizing pathogen- or danger-associated molecular patterns or abnormal host molecules. Mesenchymal stem cells (MSCs) have been reported to possess multipotency to differentiate into various cell types and immunoregulatory effects. In this study, we investigated the expression and functional regulation of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome in human umbilical cord blood-derived MSCs (hUCB-MSCs). hUCB-MSCs expressed inflammasome components that are necessary for its complex assembly. Interestingly, NLRP3 inflammasome activation suppressed the differentiation of hUCB-MSCs into osteoblasts, which was restored when the expression of adaptor proteins for inflammasome assembly was inhibited. Moreover, the suppressive effects of MSCs on T cell responses and the macrophage activation were augmented in response to NLRP3 activation. In vivo studies using colitic mice revealed that the protective abilities of hUCB-MSCs increased after NLRP3 stimulation. In conclusion, our findings suggest that the NLRP3 inflammasome components are expressed in hUCB-MSCs and its activation can regulate the differentiation capability and the immunomodulatory effects of hUCB-MSCs.

Development of an aequorin-based assay for the screening of corticotropin-releasing factor receptor antagonists (CRF1 길항제 스크리닝을 위한 에쿼린 기반 세포실험 개발연구)

  • Noh, Hyojin;Lee, Sunghou
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.11
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    • pp.7575-7581
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    • 2015
  • Corticotropin-releasing factor(CRF), one of the stress driven neuropeptides, was widely proposed to influence hair loss and re-growth. For the development of receptor antagonists, the screening system based on intracellular calcium signal process was developed and optimized. The aequorin parental cells were transfected with CRF1 receptor and alpha 16 promiscuous G protein cDNA to establish HEK293a16/hCRF1, a stable cell line for the human CRF1 receptor. In HEK293a16/hCRF1 cells, the range of sauvagine dose response was 12-fold higher($EC_{50}:15.21{\pm}1.83nM$) than in the transiently expressed cells, hence essential conditions for the antagonist screening experiments such as the robust signals and high solvent tolerance were secured. The standard antagonists for the CRF1 receptor, antalarmin and CP154526, resulted $IC_{50}$ values of $414.1{\pm}5.5$ and $290.7{\pm}1.9nM$, respectively. Similar results were presented with frozen HEK293a16/hCRF1 cells. Finally, our HEK293a16/hCRF1 cells with the aequorin based cellular functional assay can be a model system for the development of functional cosmetics and modulators that can have a clinical efficacy on hair re-growth.