• Journal of Microbiology and Biotechnology
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• 제16권10호
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• pp.1605-1612
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• 2006

Interleukin (IL)-18, a member of the family of IL-l cytokine, is one of the principal inducers of $interferon-{\gamma}(IFN-{\gamma})$ in T lymphocytes and natural killer cells. The objective of the present study was to evaluate the effect of IL-18 on the expression of chemokine IP-10 (CXCL-10) mRNA in mouse peritoneal macrophages. IL-18 had very weak direct effect or synergistic effect with IL-12 on the expression of IP-10 mRNA in C57BL/6 mouse peritoneal macrophages. However, IL-18 pretreatment was found to playa cooperative role in the expression of lipopolysaccharide (LPS)-induced IP-10 mRNA. For the expression of LPS-induced IP-10 mRNA, the synergistic effect was detected after 16 h of IL-18 pretreatment prior to LPS stimulation. The expression level of CD14 in cells stimulated with LPS was not changed by IL-18 pretreatment, and the level of $IFN-{\gamma}$ production during IL-18 pretreatment plus LPS stimulation was barely discernible ($0.36{\pm}0.31pg/ml$). Namely, the synergistic effect of IL-18 pretreatment was not related to a change of LPS receptor, CD14 expression, and the production of $IFN-{\gamma}$ by the interaction between IL-18 and LPS. The synergistic effect of IL-18 pretreatment on the expression of LPS-induced IP-10 was related to not NF-kB but AP-1 activation, and associated with the extracellular signal-regulated kinase (ERK) pathway, one of the mitogen-activated protein kinase signaling pathways. These results provide useful information that may elucidate the mechanisms underlying the effect of IL-18 on the expression of IP-10 mRNA.

• Genomics & Informatics
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• 제20권3호
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• pp.32.1-32.15
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• 2022

Malaria is a life-threatening disease, and Africa is still one of the most affected endemic regions despite years of policy to limit infection and transmission rates. Further, studies into the variable efficacy of the vaccine are needed to provide a better understanding of protective immunity. Thus, the current study is designed to delineate the effect of each dose of vaccine on the transcriptional profiles of subjects to determine its efficacy and understand the molecular mechanisms underlying the protection this vaccine provides. Here, we used gene expression profiles of pre and post-vaccination patients after various doses of RTS,S based on samples collected from the Gene Expression Omnibus datasets. Subsequently, differential gene expression analysis using edgeR revealed the significantly (false discovery rate < 0.005) 158 downregulated and 61 upregulated genes between control vs. controlled human malaria infection samples. Further, enrichment analysis of significant genes delineated the involvement of CCL8, CXCL10, CXCL11, XCR1, CSF3, IFNB1, IFNE, IL12B, IL22, IL6, IL27, etc., genes which found to be upregulated after earlier doses but downregulated after the 3rd dose in cytokine-chemokine pathways. Notably, we identified 13 cytokine genes whose expression significantly varied during three doses. Eventually, these findings give insight into the dual role of cytokine responses in malaria pathogenesis. The variations in their expression patterns after various doses of vaccination are linked to the protection as it decreases the severe inflammatory effects in malaria patients. This study will be helpful in designing a better vaccine against malaria and understanding the functions of cytokine response as well.

• BMB Reports
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• 제48권4호
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• pp.234-237
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• 2015

Aptamers, composed of single-stranded DNA or RNA oligonucleotides that interact with target molecules through a specific three-dimensional structure, are selected from pools of combinatorial oligonucleotide libraries. With their high specificity and affinity for target proteins, ease of synthesis and modification, and low immunogenicity and toxicity, aptamers are considered to be attractive molecules for development as anticancer therapeutics. Two aptamers - one targeting nucleolin and a second targeting CXCL12 - are currently undergoing clinical trials for treating cancer patients, and many more are under study. In this mini-review, we present the current clinical status of aptamers and aptamer-based cancer therapeutics. We also discuss advantages, limitations, and prospects for aptamers as cancer therapeutics. [BMB Reports 2015; 48(4): 234-237]

• 대한견주관절학회:학술대회논문집
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• 대한견주관절학회 2005년도 제13차 춘계학술대회
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• pp.42-44
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• 2005

• BMB Reports
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• 제52권1호
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• pp.42-46
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• 2019

Cellular senescence, a process of cell proliferation arrest in response to various stressors, has been considered to be important factor in age-related disease. Identification of senescent cells in tissues is limited and the role of senescent cells is poorly understood. Recently however, several studies showed the characterization of senescent cells in various pathologic conditions and the role of senescent cells in disease progression is becoming important. Senescent cells are growth-arrested cells, however, the senescence associated secretory phenotype (SASP) of senescent cells could modify the tissues' microenvironment. Here, we discuss the progress and understanding of the role of senescent cells in tissues of pathologic conditions and discuss the development of new therapeutic paradigms, such as senescent cells-targeted therapy.

• BMB Reports
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• 제49권9호
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• pp.502-507
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• 2016

To examine the effect of TBMS1on breast cancer metastasis, and investigate the potential mechanism by which Tubeimoside-1 (TBMS1) inhibits the CXCR4 expression in breast cancer cells. The expression of CXCR4 in breast cancer cell lines was determined by immunoblotting and real-time PCR. The effect of TBMS1 on NF-κB binding activity was evaluated by EMSA assay and ChIP analysis. Cell proliferation and invasion were analyzed by MTT assay and transwell invasion assay, respectively. The effect of TBMS1 on breast cancer metastasis was further evaluated in a metastasis model of nude mice. TBMS1 suppressed the expression of CXCR4 through inhibition of NF-κB binding activity. TBMS1 inhibited CXCL12-induced invasion in breast cancer cells, while ectopic expression of CXCR4 abolished the inhibitive activity of TBMS1. TBMS1 suppressed breast cancer metastasis in the metastatic model of nude mice. TBMS1 suppressed the CXCR4-mediated metastasis of breast cancer by inhibiting NF-κB binding activity.

• Journal of Ginseng Research
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• 제47권1호
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• pp.81-88
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• 2023

Background: Air pollution has led to an increased exposure of all living organisms to fine dust. Therefore, research efforts are being made to devise preventive and therapeutic remedies against fine dust-induced chronic diseases. Methods: Research of the respiratory protective effects of KRG extract in a particulate matter (PM; aerodynamic diameter of <4 ㎛) plus diesel exhaust particle (DEP) (PM4+D)-induced airway inflammation model. Nitric oxide production, expression of pro-inflammatory mediators and cytokines, and IRAK-1, TAK-1, and MAPK pathways were examined in PM4-stimulated MH-S cells. BALB/c mice exposed to PM4+D mixture by intranasal tracheal injection three times a day for 12 days at 3 day intervals and KRGE were administered orally for 12 days. Histological of lung and trachea, and immune cell subtype analyses were performed. Expression of pro-inflammatory mediators and cytokines in bronchoalveolar lavage fluid (BALF) and lung were measured. Immunohistofluorescence staining for IRAK-1 localization in lung were also evaluated. Results: KRGE inhibited the production of nitric oxide, the expression of pro-inflammatory mediators and cytokines, and expression and phosphorylation of all downstream factors of NF-κB, including IRAK-1 and MAPK/AP1 pathway in PM4-stimulated MH-S cells. KRGE suppressed inflammatory cell infiltration and number of immune cells, histopathologic damage, and inflammatory symptoms in the BALF and lungs induced by PM4+D; these included increased alveolar wall thickness, accumulation of collagen fibers, and TNF-α, MIP2, CXCL-1, IL-1α, and IL-17 cytokine release. Moreover, PM4 participates induce alveolar macrophage death and interleukin-1α release by associating with IRAK-1 localization was also potently inhibited by KRGE in the lungs of PM4+D-induced airway inflammation model. KRGE suppresses airway inflammatory responses, including granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines via inhibition of IRAK-1 and MAPK pathway. Conclusion: Our results indicate the potential of KRGE to serve as an effective therapeutic agent against airway inflammation and respiratory diseases.

• 생명과학회지
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• 제19권8호
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• pp.1067-1072
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• 2009

성체흰쥐의 경우 항암제인 싸이클로포스파마이드(CY)처리로 퇴축된 가슴샘은 2주 후에 정상조직으로 재생된다. 가슴샘 발생과정에서 이미 알려진 SDF-1 신호전달의 중요성과는 달리 성체의 가슴샘 재생과정에서 그 역할에 관해서는 알려진 바 전혀 없다. 본 연구의 목적은 발생중인 가슴샘에서 발현이 증가된다고 이미 알려져 있는 SDF-1이 성체의 가슴샘재생과정에서 어떤 발현 양상을 보이는지를 조사하는 것이다. 본 연구에서는 사이클로포스파마이(cyclophosphamide: CY)를 투여하여 가슴샘의 급성 퇴축을 유발시킨 후, 가슴샘 재생과정동안 SDF-1의 발현 특성을 면역조직화학, 이중면역염색 형광법, 역전사 중합효소 연쇄반응법을 이용하여 조사하였다. 그 결과, SDF-1은 가슴샘의 급성 퇴축 이후 7일째 되는 시기에 mRNA와 단백질의 양이 급격히 증가하였으며, 이중면역염색 형광법을 통해 큰포식 세포와 위치적 분포가 일치함을 확인하였다. 따라서, 본 연구 결과들을 통해 SDF-1은 가슴샘의 급성 퇴축 초기 과정에서 나타나는 손상된 세포를 처리하는 큰포식 세포의 기능 조절에 관여할 것으로 생각된다.

• Clinical and Experimental Reproductive Medicine
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• 제50권1호
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• pp.44-52
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• 2023

Objective: The DNA integrity of spermatozoa that attach to fallopian tube (FT) cells is higher than spermatozoa that do not attach. FT epithelial cells can distinguish normal and abnormal sperm chromatin. This study investigated the effects of sperm with a high-DNA fragmentation index (DFI) from men with unexplained repeated implantation failure (RIF) on the Toll-like receptor (TLR) signaling pathway in human FT cells in vitro. Methods: Ten men with a RIF history and high-DFI and 10 healthy donors with low-DFI comprised the high-DFI (>30%) and control (<30%) groups, respectively. After fresh semen preparation, sperm were co-cultured with a human FT epithelial cell line (OE-E6/E7) for 24 hours. RNA was extracted from the cell line and the human innate and adaptive immune responses were tested using an RT2 profiler polymerase chain reaction (PCR) array. Results: The PCR array data showed significantly higher TLR-1, TLR-2, TLR-3, TLR-6, interleukin 1α (IL-1α), IL-1β, IL-6, IL-12, interferon α (IFN-α), IFN-β, tumor necrosis factor α (TNF-α), CXCL8, GM-CSF, G-CSF, CD14, ELK1, IRAK1, IRAK2, IRAK4, IRF1, IRF3, LY96, MAP2K3, MAP2K4, MAP3K7, MAP4K4, MAPK8, MAPK8IP3, MYD88, NFKB1, NFKB2, REL, TIRAP, and TRAF6 expression in the high-DFI group than in the control group. These factors are all involved in the TLR-MyD88 signaling pathway. Conclusion: The MyD88-dependent pathway through TLR-1, TLR-2, and TLR-6 activation may be one of the main inflammatory pathways activated by high-DFI sperm from men with RIF. Following activation of this pathway, epithelial cells produce inflammatory cytokines, resulting in neutrophil infiltration, activation, phagocytosis, neutrophil extracellular trap formation, and apoptosis.