• Title/Summary/Keyword: integrative analysis

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Mechanisms of Resorcinol Antagonism of Benzo[a]pyrene-Induced Damage to Human Keratinocytes

  • Lee, Seung Eun;Kwon, Kitae;Oh, Sae Woong;Park, Se Jung;Yu, Eunbi;Kim, Hyeyoun;Yang, Seyoung;Park, Jung Yoen;Chung, Woo-Jae;Cho, Jae Youl;Lee, Jongsung
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.227-233
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    • 2021
  • Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and ubiquitous environmental toxin with known harmful effects to human health. Abnormal phenotypes of keratinocytes are closely associated with their exposure to B[a]P. Resorcinol is a component of argan oil with reported anticancer activities, but its mechanism of action and potential effect on B[a]P damage to the skin is unknown. In this study, we investigated the effects of resorcinol on B[a]P-induced abnormal keratinocyte biology and its mechanisms of action in human epidermal keratinocyte cell line HaCaT. Resorcinol suppressed aryl hydrocarbon receptor (AhR) activity as evidenced by the inhibition of B[a]P-induced xenobiotic response element (XRE)-reporter activation and cytochrome P450 1A1 (CYP1A1) expression. In addition, resorcinol attenuated B[a]P-induced nuclear translocation of AhR, and production of ROS and pro-inflammatory cytokines. We also found that resorcinol increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activity. Antioxidant response element (ARE)-reporter activity and expression of ARE-dependent genes NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase-1 (HO-1) were increased by resorcinol. Consistently, resorcinol treatment induced nuclear localization of Nrf2 as seen by Western analysis. Knockdown of Nrf2 attenuated the resorcinol effects on ARE signaling, but knockdown of AhR did not affect resorcinol activation of Nrf2. This suggests that activation of antioxidant activity by resorcinol is not mediated by AhR. These results indicate that resorcinol is protective against effects of B[a]P exposure. The mechanism of action of resorcinol is inhibition of AhR and activation of Nrf2-mediated antioxidant signaling. Our findings suggest that resorcinol may have potential as a protective agent against B[a]P-containing pollutants.

Production and characterization of lentivirus vector-based SARS-CoV-2 pseudoviruses with dual reporters: Evaluation of anti-SARS-CoV-2 viral effect of Korean Red Ginseng

  • Jeonghui Moon;Younghun Jung;Seokoh Moon;Jaehyeon Hwang;Soomin Kim;Mi Soo Kim;Jeong Hyeon Yoon;Kyeongwon Kim;Youngseo Park;Jae Youl Cho;Dae-Hyuk Kweon
    • Journal of Ginseng Research
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    • v.47 no.1
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    • pp.123-132
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    • 2023
  • Background: Pseudotyped virus systems that incorporate viral proteins have been widely employed for the rapid determination of the effectiveness and neutralizing activity of drug and vaccine candidates in biosafety level 2 facilities. We report an efficient method for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus with dual luciferase and fluorescent protein reporters. Moreover, using the established method, we also aimed to investigate whether Korean Red Ginseng (KRG), a valuable Korean herbal medicine, can attenuate infectivity of the pseudotyped virus. Methods: A pseudovirus of SARS-CoV-2 (SARS-2pv) was constructed and efficiently produced using lentivirus vector systems available in the public domain by the introduction of critical mutations in the cytoplasmic tail of the spike protein. KRG extract was dose-dependently treated to Calu-3 cells during SARS2-pv treatment to evaluate the protective activity against SARS-CoV-2. Results: The use of Calu-3 cells or the expression of angiotensin-converting enzyme 2 (ACE2) in HEK293T cells enabled SARS-2pv infection of host cells. Coexpression of transmembrane protease serine subtype 2 (TMPRSS2), which is the activator of spike protein, with ACE2 dramatically elevated luciferase activity, confirming the importance of the TMPRSS2-mediated pathway during SARS-CoV-2 entry. Our pseudovirus assay also revealed that KRG elicited resistance to SARS-CoV-2 infection in lung cells, suggesting its beneficial health effect. Conclusion: The method demonstrated the production of SARS-2pv for the analysis of vaccine or drug candidates. When KRG was assessed by the method, it protected host cells from coronavirus infection. Further studies will be followed for demonstrating this potential benefit.

Inhibitory Effects of Flavonoids from Lespedeza cuneata on Aldose Reductase

  • Quilantang, Norman;Lee, Ju Sung;Yun, Young-Sok;Limbo, Carlo;Yoo, Sang Woo;Lee, Seong;Lee, Sanghyun
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.04a
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    • pp.62-62
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    • 2018
  • Inhibition of aldose reductase (AR) has been shown to prevent the onset and progression of many diabetic complications wherein several AR inhibitors were isolated from plants abundant in polyphenolic compounds. Lespedeza cuneata (Fabaceae), a perennial plant indigenous in East Asian countries, is shown to be abundant in these polyphenolic substances such as flavonoids and tannins. However, there are no studies to date regarding its effects on AR. In this study, the inhibitory activity of the methanol extract and stepwise polarity fractions of Lespedeza cuneata on AR was investigated. The bioactive compounds purified from L. cuneata by repeated column chromatography were also tested for AR inhibition. Results show that the ethyl acetate and n-butanol fractions of L. cuneata exhibited potent inhibition against AR with $IC_{50}$ values of 0.57 and $0.49{\mu}g/mL$, respectively. Further analysis led to the isolation of acacetin (1), afzelin (2), astragalin (3), kaempferol (4), and scutellarein 7-O-glucoside (5). The AR inhibitory effects these five compounds were also determined in which compounds 2, 3, and 5 showed potent AR inhibitory effects with $IC_{50}$ values of 2.20, 1.91, and $12.87{\mu}M$, respectively. Quantitative analysis of astragalin (3) by HPLC-UV was also performed in the leaves and roots of L. cuneata (0.626 and 0.671 mg/g, respectively). This study reports that the flavonoids isolated from L. cuneata show promising AR inhibitory activities which can be further developed as natural therapies for treating and managing diabetic complications.

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The Effect of Success Factors on SCM Performance in Fashion Industry Stream (패션산업 스트림에 따라 SCM 성공요인이 SCM 성과에 미치는 영향연구)

  • Choi, Jin-Hyeok;Shin, Sang-Moo
    • Journal of Fashion Business
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    • v.16 no.2
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    • pp.12-26
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    • 2012
  • Fashion industry characteristically goes through many steps to manufacture and to retail apparel products. Complex inter-industry channels with many intermediaries in fashion industry provoked many problems regarding recognizing customer's need, delivering time, flexibility, and inventory control. Therefore, the purposes of this study were to investigate the differences between apparel manufacturing and distribution process in SCM success factors and performances, and to investigate how SCM success factors affect on performances. Questionnaire was developed and distributed to apparel industry. The returned 116 questionnaires were analyzed by Cronbach's alpha for internal validity, factor analysis, t-test, and regression analysis with SPSS14.0. The results of this study were as follows: There was significant difference of SCM success factors between apparel manufacturing and distribution regarding process standardization and integration. There were significant differences of SCM performances such as reaction for customer, flexible management, cost minimization, and maximized asset utilization which distribution was higher than apparel manufacturing process. In apparel manufacturing, SC strategic relation, and integrative management influenced upon reaction for customer of SCM performances. SC integrative management influenced upon cost minimization. SC integrative management influenced upon maximized asset utilization. In distribution, SC strategic relation, and activated support for SCM influenced upon reaction for customer of SCM performances. SCM specialization, credible relationship among supply chains, activated support for SCM, and SC integrative management influenced upon cost minimization. SCM specialization, credible relationship among supply chains, and SC integrative management influenced upon maximized asset utilization.

Deciphering the Role of Tyrosine Sulfation in Xanthomonas oryzae pv. oryzae Using Shotgun Proteomic Analysis

  • Park, Hye-Jee;Park, Chang-Jin;Bae, Nahee;Han, Sang-Wook
    • The Plant Pathology Journal
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    • v.32 no.3
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    • pp.266-272
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    • 2016
  • A bacterial tyrosine sulfotransferase, RaxST, is required for activation of rice XA21-mediated immunity, and it catalyzes sulfation of tyrosine residues of Omp1X and RaxX in Xanthomonas oryzae pv. oryzae, a causal agent of bacterial blight in rice. Although RaxST is biochemically well-characterized, biological functions of tyrosine sulfation have not been fully elucidated. We compared protein expression patterns between the wildtype and a raxST knockout mutant using shotgun proteomic analysis. Forty nine proteins displayed a more than 1.5-fold difference in their expression between the wildtype and the mutant strains. Clusters of orthologous groups analysis revealed that proteins involved in cell motility were most abundant, and phenotypic observation also showed that the twitching motility of the mutant was dramatically changed. These results indicate that tyrosine sulfation by RaxST is essential for Xoo movement, and they provide new insights into the biological roles of RaxST in cellular processes.

An Integrative Method of FTA and FMEA for Software Security Analysis of a Smart Phone (스마트 폰의 소프트웨어 보안성 분석을 위한 FTA와 FMEA의 통합적 방법)

  • Kim, Myong-Hee;Toyib, Wildan;Park, Man-Gon
    • KIPS Transactions on Computer and Communication Systems
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    • v.2 no.12
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    • pp.541-552
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    • 2013
  • Recently software security of the smart phone is an important issue in the field of information science and technology due to fast propagation of smart technology in our life. The smart phone as the security critical systems which are utilizing in terminal systems of the banking, ubiquitous home management, airline passengers screening, and so on are related to the risk of costs, risk of loss, risk of availability, and risk by usage. For the security issues, software hazard analysis of smart phone is the key approaching method by use of observed failures. In this paper, we propose an efficient integrative framework for software security analysis of the smart phone using Fault Tree Analysis (FTA) and Failure Mode Effect Analysis (FMEA) to gain a convergence security and reliability analysis technique on hand handle devices. And we discuss about that if a failure mode effect analysis performs simpler, not only for improving security but also reducing failure effects on this smart device, the proposed integrative framework is a key solution.

Spirituality: Concept Analysis (영성(Spirituality) 개념 분석)

  • O, Bok-Ja;Gang, Gyeong-A
    • Journal of Korean Academy of Nursing
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    • v.30 no.5
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    • pp.1145-1155
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    • 2000
  • The purpose of this study is to explore the concept spirituality and to gain understanding of nursing intervention that may improve spiritual well-being. The concept analysis framework developed by Walker and Avant (1995) was used to clarify the concept. In the study, 'Harmonious interconnectedness', 'Transcendence', 'Integrative Energy' and 'Purpose and Meaning in Life' emerged as the critical attributes of spirituality. The first attribute, 'harmonious Inter- connectedness', has three categories including intrapersonal, (self), interpersonal (others/ nature) and transpersonal (the Supreme Being). The second attribute, 'Transcendence', is defined as the ability to extend one's own self beyond the limits of usual experiences and to achieve new perspectives. This attribute is demonstrated by 'coping with situations', to 'self-healing', and 'transformation'. The third attribute of spirituality is 'Integrative Energy', which integrates all dimensions and acts as a creative and dynamic force that keeps a person growing and changing. 'Integrative Energy is also defined as an inner resource that gives a sense of empowerment. Therefore the highly spiritual person demonstrate 'inner peace', 'growing', 'inner strength,' and 'well-being'. The fourth attribute 'Purpose and Meaning in Life' represents a sense of connectedness with one's inner values and with a greater purpose in life. It is demonstrated by 'hope' and 'a powerful life'. In this study, the antecedents of the spirituality represented as 'spirit' and its potential enablers were 'Introspection/reflection', 'Interconnectedness with all living things', and an 'Awareness of a Higher-Power'. The consequences of this concept may be described as 'physical, psychosocial, and spiritual well-being'. Empirical referents of this are 'purposeful life' 'self-worth' 'hope' 'love' 'service' 'forgiveness' 'trust/belief' 'inner peace' 'self-actualization' 'religious practices' 'transformation' 'inner strength' and 'coping'. In conclusion, spirituality can be defined based on these critical attributes. Spirituality is a dynamic, integrative energy based on a feeling of harmonious interconnection with self, others and a higher power. Through it, one is enabled to transcend and to live with meaning and purpose in life.

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Reliability of microarray analysis for studying periodontitis: low consistency in 2 periodontitis cohort data sets from different platforms and an integrative meta-analysis

  • Jeon, Yoon-Seon;Shivakumar, Manu;Kim, Dokyoon;Kim, Chang-Sung;Lee, Jung-Seok
    • Journal of Periodontal and Implant Science
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    • v.51 no.1
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    • pp.18-29
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    • 2021
  • Purpose: The aim of this study was to compare the characteristic expression patterns of advanced periodontitis in 2 cohort data sets analyzed using different microarray platforms, and to identify differentially expressed genes (DEGs) through a meta-analysis of both data sets. Methods: Twenty-two patients for cohort 1 and 40 patients for cohort 2 were recruited with the same inclusion criteria. The 2 cohort groups were analyzed using different platforms: Illumina and Agilent. A meta-analysis was performed to increase reliability by removing statistical differences between platforms. An integrative meta-analysis based on an empirical Bayesian methodology (ComBat) was conducted. DEGs for the integrated data sets were identified using the limma package to adjust for age, sex, and platform and compared with the results for cohorts 1 and 2. Clustering and pathway analyses were also performed. Results: This study detected 557 and 246 DEGs in cohorts 1 and 2, respectively, with 146 and 42 significantly enriched gene ontology (GO) terms. Overlapping between cohorts 1 and 2 was present in 59 DEGs and 18 GO terms. However, only 6 genes from the top 30 enriched DEGs overlapped, and there were no overlapping GO terms in the top 30 enriched pathways. The integrative meta-analysis detected 34 DEGs, of which 10 overlapped in all the integrated data sets of cohorts 1 and 2. Conclusions: The characteristic expression pattern differed between periodontitis and the healthy periodontium, but the consistency between the data sets from different cohorts and metadata was too low to suggest specific biomarkers for identifying periodontitis.

A possible mechanism to the antidepressant-like effects of 20 (S)-protopanaxadiol based on its target protein 14-3-3 ζ

  • Chen, Lin;Li, Ruimei;Chen, Feiyan;Zhang, Hantao;Zhu, Zhu;Xu, Shuyi;Cheng, Yao;Zhao, Yunan
    • Journal of Ginseng Research
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    • v.46 no.5
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    • pp.666-674
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    • 2022
  • Background: Ginsenosides and their metabolites have antidepressant-like effects, but the underlying mechanisms remain unclear. We previously identified 14-3-3 ζ as one of the target proteins of 20 (S)-protopanaxadiol (PPD), a fully deglycosylated ginsenoside metabolite. Methods: Corticosterone (CORT) was administered repeatedly to induce the depression model, and PPD was given concurrently. The tail suspension test (TST) and the forced swimming test (FST) were used for behavioral evaluation. All mice were sacrificed. Golgi-cox staining, GSK 3β activity assay, and Western blot analysis were performed. In vitro, the kinetic binding analysis with the Biolayer Interferometry (BLI) was used to determine the molecular interactions. Results: TST and FST both revealed that PPD reversed CORT-induced behavioral deficits. PPD also ameliorated the CORT-induced expression alterations of hippocampal Ser9 phosphorylated glycogen synthase kinase 3β (p-Ser9 GSK 3β), Ser133 phosphorylated cAMP response element-binding protein (p-Ser133 CREB), and brain-derived neurotrophic factor (BDNF). Moreover, PPD attenuated the CORT-induced increase in GSK 3β activity and decrease in dendritic spine density in the hippocampus. In vitro, 14-3-3 ζ protein specifically bound to p-Ser9 GSK 3β polypeptide. PPD promoted the binding and subsequently decreased GSK 3β activity. Conclusion: These findings demonstrated the antidepressant-like effects of PPD on the CORT-induced mouse depression model and indicated a possible target-based mechanism. The combination of PPD with the 14-3-3 ζ protein may promote the binding of 14-3-3 ζ to p-GSK 3β (Ser9) and enhance the inhibition of Ser9 phosphorylation on GSK 3β kinase activity, thereby activating the plasticity-related CREBeBDNF signaling pathway.

Tumor hypoxia and reoxygenation: the yin and yang for radiotherapy

  • Hong, Beom-Ju;Kim, Jeongwoo;Jeong, Hoibin;Bok, Seoyeon;Kim, Young-Eun;Ahn, G-One
    • Radiation Oncology Journal
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    • v.34 no.4
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    • pp.239-249
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    • 2016
  • Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of 'reoxygenation' phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because 'reoxygenation' is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn't it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy.