• Journal of Haehwa Medicine
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• v.21 no.1
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• pp.11-21
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• 2012

New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients. The purpose of this study is to develop novel immune suppressants for PTDM using of action mechanism of them. The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to ${\beta}$-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of ${\beta}$-cells to therapeutical levels of tacrolimus (FK506) or cyclosporin A(CsA). The immunosuppressive drug cyclosporine(CsA) is a potent agent widely used after organ transplantations and various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity. The renal or vascular toxicity is influenced by the degree of the endothelial damage. FK506(tacrolimus) is a widely used immunosuppressive agent in the treatment of various medical conditions, including autoimmune disease, bone marrow and organ transplantations. We found some interesting clusters and confirmed the feasibility of cDNA microarray in the study of Immunosuppressant. In this study, we investigated gene expression patterns induced by Immunosuppressant in RIN-m5F of rat insulinoma cell line. Gene expressions evaluated using cDNA microarry in two clusters were increased or decreased. this study provides comprehensive comparison of the patterns of gene expression changes induced by CsA and FK506 in ${\beta}$-cells. This study could establish that the mode of action mechanism by which currently used insulin inhibitors inducing PTDM could be elucidated at least in part, which raises the possibility that novel immune suppressive PTDM can be developed. The molecular biological study on PTDM will also contribute the progress in diabetes research field as well as in that of PTDM.

• Molecular & Cellular Toxicology
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• v.1 no.4
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• pp.230-236
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• 2005

Formaldehyde is a common environmental contaminant found in tobacco smoke, paint, garments, diesel and exhaust, and medical and industrial products. Formaldehyde has been considered to be potentially carcinogenic, making it a subject of major environmental concern. However, only a little information on the mechanism of immunological sensitization and asthma by this compound has been known. So, we performed with Jurkat cell line, a human T lymphocyte, to assess the induction of DNA damage and to identify the DEGs related to immune response or toxicity by formaldehyde. In this study, we investigated the induction of DNA single strand breaks by formaldehyde using single cell gel electrophoresis assay (comet assay). And we compared gene expression between control and formaldehyde treatment to identify genes that are specifically or predominantly expressed by employing annealing control primer (ACP)-based $GeneFishing^{TM}$ method. The cytotoxicity ($IC_{30}$) of formaldehyde was determined above the 0.65 mM in Jurkat cell in 48 h treatment. Based on the $IC_{30}$ value from cytotoxicity test, we performed the comet assay in this concentration. From these results, 0.65 mM of formaldehyde was not revealed significant DNA damages in the absence of S-9 metabolic activation system. And the one differentially expressed gene (DEG) of formaldehyde was identified to zinc finger protein 292 using $GeneFishing^{TM}$ method. Through further investigation, we will identify more meaningful and useful DEGs on formaldehyde, and then can get the information on the associated mechanism and pathway with immune response or other toxicity by formaldehyde exposure.

• Fisheries and Aquatic Sciences
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• v.9 no.1
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• pp.14-21
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• 2006

The aim of this study was to investigate in vivo toxicity and effects of two phthalate esters (PEs), di-n-butylphthalate (DBP) and di-2-ethylhexyl phthalate (DEHP), on the immune system of the bagrid catfish, Pseudobagrus fulvidraco. Groups of experimental fish were subjected to daily intraperitoneal injections of 300 or 1000 mg $kg^{-1}$ of DBP or DEHP for 3 days, and the cellularity and functional activity of phagocytes were measured in the spleen and pronephros (head kidney). The number of spleen leukocyte cells increased significantly (p<0.05) in response to low and high doses of DEHP and DBP, respectively; however, the cellularity of the pronephros was more susceptible to higher dose of DEHP than DBP. Nonspecific immunity, as determined by the phagocytic index (PI) and phagocytic capacity (PC), was significantly depressed by DEHP at 1000 $1000mg\;kg^{-1}\;day^{-1}$ in the pronephros at 3 days after injection. Furthermore, significantly (p<0.05) increased levels of serum glutamic oxaloacetate transaminase (GOT) and glutamic pyruvate transaminase (GPT) indicated marked hepatic dysfunction in immunosuppressed fish. Treated fish showed a significant reduction in total serum protein but no significant alteration in lysozyme activity. These results demonstrate the sensitivity of the fish immune response for predicting PE-induced immunotoxicity.

• Journal of the Korean Institute of Intelligent Systems
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• v.12 no.5
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• pp.411-416
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• 2002

Recently, the trial and success of malicious cyber attacks has been increased rapidly with spreading of Internet and the activation of a internet shopping mall and the supply of an online internet, so it is expected to make a problem more and more. Currently, the general security system based on Internet couldn't cope with the attack properly, if ever, other regular systems have depended on common softwares to cope with the attack. In this paper, we propose the positive selection mechanism and negative selection mechanism of T-cell, which is the biological distributed autonomous system, to develop the self/non-self recognition algorithm, the anomalous behavior detection algorithm, and AIS (Artificial Immune System) that is easy to be concrete on the artificial system. The proposed algorithm can cope with new intrusion as well as existing one to intrusion detection system in the network environment.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.383-389
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• 2011

Background: EY-6 is one of the newly synthesized indoledione derivatives to induce tumor cell-specific cell death. In this study, we investigated the mechanism of immunological death induced by EY-6 at mouse colon cancer cell as well as at the normal immune cell represented by dendritic cell. Methods: C57BL/6 mouse syngeneic colon cancer cell MC38 was treated with EY-6, and analyzed by MTT for viability test, flow cytometry for confirming surface expressing molecules and ELISA for detection of cytokine secretion. Normal myeloid-dendritic cell (DC) was ex vivo cultured from bone marrow hematopoietic stem cells of C57BL/6 mice with GM-CSF and IL-4 to analyze the DC uptake of dead tumor cells and to observe the effect of EY-6 on the normal DC. Results: EY-6 killed the MC38 tumor cells in a dose dependent manner (25, 50 and $100{\mu}M$) with carleticulin induction. And EY-6 induced the secretion of IFN-${\gamma}$ but not of TNF-${\alpha}$ from the MC38 tumor cells. EY-6 did not kill the ex-vivo cultured DCs at the dose killing tumor cells and did slightly but not significantly induced the DC maturation. The OVA-specific cross-presentation ability of DC was not induced by chemical treatment (both MHC II and MHC I-restricted antigen presentation). Conclusion: Data indicate that the EY-6 induced tumor cell specific and immunological cell death by modulation of tumor cell phenotype and cytokine secretion favoring induction of specific immunity eliminating tumor cells.

• The Plant Pathology Journal
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• v.36 no.3
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• pp.255-266
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• 2020

Plant immune responses can be triggered by chemicals, microbes, pathogens, insects, or abiotic stresses. In particular, induced systemic resistance (ISR) refers to the activation of the immune system due to a plant's interaction with beneficial microorganisms. The phenolic compound, 2,4-diacetylphloroglucinol (DAPG), which is produced by beneficial Pseudomonas spp., acts as an ISR elicitor, yet DAPG's mechanism in ISR remains unclear. In this study, transgenic Arabidopsis thaliana plants overexpressing the DAPG hydrolase gene (phlG) were generated to investigate the functioning of DAPG in ISR. DAPG was applied onto 3-week-old A. thaliana Col-0 and these primed plants showed resistance to the pathogens Botrytis cinerea and Pseudomonas syringae pv. tomato DC3000. However, in the phlG transgenic A. thaliana, the ISR was not triggered against these pathogens. The DAPG-mediated ISR phenotype was impaired in transgenic A. thaliana plants overexpressing phlG, thus showing similar disease severity when compared to untreated control plants. Furthermore, the DAPG-treated A. thaliana Col-0 showed an increase in their gene expression levels of PDF1.2 and WRKY70 but this failed to occur in the phlG transgenic lines. Collectively, these experimental results indicate that jasmonic acid/ethylene signal-based defense system is effectively disabled in phlG transgenic A. thaliana lines.

• The Korean Journal of Pain
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• v.34 no.4
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• pp.463-470
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• 2021

Background: Although neuropathic pain is a severe and common pain, its pathophysiology has not been elucidated yet. Studies in recent years have focused on the immune system's role in the pathogenesis of neuropathic pain. The aim of this study was to investigate the role of immunological mechanisms in neuropathic pain and the effect of pregabalin by measuring immunological marker levels in peripheral blood before and after pregabalin treatment in postherpetic neuralgia (PHN) patients with neuropathic pain. Methods: Forty patients diagnosed with PHN were included in the study. CD4, T follicular cells (Tfh: CD4⁺CXCR5⁺PD1⁺), Th17 (CD4⁺CCR6⁺ and CD4⁺IL17A⁺), regulatory T cells (Treg: CD4⁺ CD25⁺foxp3⁺), Th1 (CD4⁺ CXCR3⁺ and CD4⁺ IFN-γ⁺) and Th2 (CD4⁺ IL-4⁺) cell ratios were measured in peripheral blood samples before treatment and after 3 months of treatment. Results: When immunological marker and inflammation parameter levels were compared before and after treatment, the helper T cell ratio (CD3⁺, CD4⁺) was 30.28 ± 12.27% before treatment and 34.93 ± 11.70% after treatment, so there was a statistically significant increase (P = 0.028). Th17 was 4.75 ± 5.02% before treatment and 5.80 ± 3.13% after treatment, and there was a statistically significant increase (P = 0.036). Conclusions: Immunological mechanisms play an essential role in the pathogenesis of neuropathic pain, immunologically based treatment approach will be the critical point of treatment.

• BMB Reports
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• v.52 no.1
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• pp.56-63
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• 2019

Aging is a complex and progressive process characterized by physiological and functional decline with time that increases susceptibility to diseases. Aged-related functional change is accompanied by a low-grade, unresolved chronic inflammation as a major underlying mechanism. In order to explain aging in the context of chronic inflammation, a new integrative concept on age-related chronic inflammation is necessary that encompasses much broader and wider characteristics of cells, tissues, organs, systems, and interactions between immune and non-immune cells, metabolic and non-metabolic organs. We have previously proposed a novel concept of senescent (seno)-inflammation and provided its frameworks. This review summarizes senoinflammation concept and additionally elaborates modulation of senoinflammation by calorie restriction (CR). Based on aging and CR studies and systems-biological analysis of Omics big data, we observed that senescence associated secretory phenotype (SASP) primarily composed of cytokines and chemokines was notably upregulated during aging whereas CR suppressed them. This result further strengthens the novel concept of senoinflammation in aging process. Collectively, such evidence of senoinflammation and modulatory role of CR provide insights into aging mechanism and potential interventions, thereby promoting healthy longevity.

• IMMUNE NETWORK
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• v.2 no.4
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• pp.183-188
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• 2002

Gradual attrition of telomere to a critical short length elicits successive cellular response of cellular senescence and crisis. Cancer cells evade this process by maintaining functional telomeres via one of two known mechanisms of telomere maintenance. The first and most frequent mechanism involves reactivation of enzyme activity of telomerase, a ribonucleoprotein complex mainly via transcriptional up-regulation of TERT, a catalytic subunit of telomerase complex. The second mechanism utilizes telomerase-independent way termed ALT (for Alternative Lengthening of Telomere), which possibly involves recombination pathways. Thus master key for cellular immortalization is supposed to possess adequate telomere reserves. Indeed, telomerase can alone induce the immortalization under culture on feeder cell layers without generally known inactivation mechanism of tumor suppressor genes. Including this phenomena, this review will focus on telomerase and telomere-associated proteins, thereby implication of these proteins for cellular immortalization processes.

• IMMUNE NETWORK
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• v.21 no.5
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• pp.36.1-36.16
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• 2021

Peroxiredoxins (Prxs) are ubiquitously expressed peroxidases that reduce hydrogen peroxide or alkyl peroxide production in cells. Prxs are released from cells in response to various stress conditions, and they function as damage-associated molecular pattern molecules. However, the secretory mechanism of Prxs and their roles have not been elucidated. Thus, we aimed to determine whether inflammasome activation is a secretory mechanism of Prxs and subsequently identify the effect of the secreted Prxs on activation of the classical complement pathway. Using J774A.1, a murine macrophage cell line, we demonstrated that NLRP3 inflammasome activation induces Prx1, Prx2, Prx5, and Prx6 secretion in a caspase-1 dependent manner. Using HEK293T cells with a transfection system, we revealed that the release of Prx1 and Prx2 relies on gasdermin-D (GSDMD)-mediated secretion. Next, we confirmed the binding of both Prx1 and Prx2 to C1q; however, only Prx2 could induce the C1q-mediated classical complement pathway activation. Collectively, our results suggest that inflammasome activation is a secretory mechanism of Prxs and that GSDMD is a mediator of their secretion. Moreover, secreted Prx1 and Prx2 bind with C1q, but only Prx2 mediates the classical complement pathway activation.