• Title/Summary/Keyword: Cell complex

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Clinical efficacy and mechanism of probiotics in allergic diseases

  • Kim, Ha-Jung;Kim, Hyung Young;Lee, So-Yeon;Seo, Ju-Hee;Lee, Eun;Hong, Soo-Jong
    • Clinical and Experimental Pediatrics
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    • v.56 no.9
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    • pp.369-376
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    • 2013
  • A complex interplay between genetic and environmental factors partially contributes to the development of allergic diseases by affecting development during prenatal and early life. To explain the dramatic increase in the prevalence of allergic diseases, the hygiene hypothesis proposed that early exposure to infection prevented allergic diseases. The hygiene hypothesis has changed to the microbial hypothesis, in which exposure to microbes is closely linked to the development of the early immune system and allergic diseases. The intestinal flora may contribute to allergic disease through its substantial effect on mucosal immunity. Based on findings that exposure to microbial flora early in life can change the Th1/Th2 balance, thus favoring a Th1 cell response, probiotics may be beneficial in preventing allergic diseases. However, evidence from clinical and basic research to prove the efficacy of probiotics in preventing allergy is lacking. To date, studies have yielded inconsistent findings on the usefulness of probiotics in allergic diseases. It is difficult to demonstrate an exact effect of probiotics on asthma, allergic rhinitis, and food allergy because of study limitations, such as different first supplementation period, duration, different strains, short follow-up period, and host factors. However, many studies have demonstrated a significant clinical improvement in atopic dermatitis with the use of probiotics. An accurate understanding of the development of human immunity, intestinal barrier function, intestinal microbiota, and systemic immunity is required to comprehend the effects of probiotics on allergic diseases.

NSAID Activated Gene (NAG-1), a Modulator of Tumorigenesis

  • Eling, Thomas E.;Baek, Seung-Joon;Shim, Min-sub;Lee, Chang-Ho
    • BMB Reports
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    • v.39 no.6
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    • pp.649-655
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    • 2006
  • The NSAID activated gene (NAG-1), a member of the TGF-$\beta$ superfamily, is involved in tumor progression and development. The over-expression of NAG-1 in cancer cells results in growth arrest and increase in apoptosis, suggesting that NAG-1 has anti-tumorigenic activity. This conclusion is further supported by results of experiments with transgenic mice that ubiquitously express human NAG-1. These transgenic mice are resistant to the development of intestinal tumors following treatment with azoxymethane or by introduction of a mutant APC gene. In contrast, other data suggest a pro-tumorigenic role for NAG-1, for example, high expression of NAG-1 is frequently observed in tumors. NAG-1 may be like other members of the TGF-$\beta$ superfamily, acting as a tumor suppressor in the early stages, but acting pro-tumorigenic at the later stages of tumor progression. The expression of NAG-1 can be increased by treatment with drugs and chemicals documented to prevent tumor formation and development. Most notable is the increase in NAG-1 expression by the inhibitors of cyclooxygenases that prevent human colorectal cancer development. The regulation of NAG-1 is complex, but these agents act through either p53 or EGR-1 related pathways. In addition, an increase in NAG-1 is observed in inhibition of the AKT/GSK-$3{\beta}$ pathway, suggesting NAG-1 alters cell survival. Thus, NAG-1 expression is regulated by tumor suppressor pathways and appears to modulate tumor progression.

Adjuvant effect of liposome-encapsulated natural phosphodiester CpG-DNA

  • Kim, Dong-Bum;Kwon, Sang-Hoon;Ahn, Chi-Seok;Lee, Young-Hee;Choi, Soo-Young;Park, Jin-Seu;Kwon, Hyeok-Yil;Kwon, Hyung-Joo
    • BMB Reports
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    • v.44 no.11
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    • pp.758-763
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    • 2011
  • Immunostimulatory CpG-DNA targeting TLR9 is one of the most extensively evaluated vaccine adjuvants. Previously, we found that a particular form of natural phosphodiester bond CpG-DNA (PO-ODN) encapsulated in a phosphatidyl-${\beta}$-oleoyl-${\gamma}$-palmitoyl ethanolamine (DOPE) : cholesterol hemisuccinate (CHEMS) (1 : 1 ratio) complex (Lipoplex(O)) is a potent adjuvant. Complexes containing peptide and Lipoplex(O) are extremely useful for B cell epitope screening and antibody production without carriers. Here, we showed that IL-12 production was increased in bone marrow derived dendritic cells in a CpG sequence-dependent manner when PO-ODN was encapsulated in Lipoplex(O), DOTAP or lipofectamine. However, the effects of Lipoplex(O) surpassed those of PO-ODN encapsulated in DOTAP or lipofectamine and also other various forms of liposome-encapsulated CpG-DNA in terms of potency for protein antigen-specific IgG production and Th1- associated IgG2a production. Therefore, Lipoplex(O) may have a unique potent immunoadjuvant activity which can be useful for various applications involving protein antigens as well as peptides.

PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model

  • Hwang, Hyun Sook;Park, In Young;Kim, Dae Won;Choi, Soo Young;Jung, Young Ok;Kim, Hyun Ah
    • BMB Reports
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    • v.48 no.7
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    • pp.407-412
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    • 2015
  • The 12 kDa FK506-binding protein (FK506BP12), an immunosuppressor, modulates T cell activation via calcineurin inhibition. In this study, we investigated the ability of PEP-1-FK506BP12, consisting of FK506BP12 fused to the protein transduction domain PEP-1 peptide, to suppress catabolic responses in primary human chondrocytes and in a mouse carrageenan-induced paw arthritis model. Western blotting and immunofluorescence analysis showed that PEP-1-FK506BP12 efficiently penetrated chondrocytes and cartilage explants. In interleukin-1β (IL-1β)-treated chondrocytes, PEP-1-FK506BP12 significantly suppressed the expression of catabolic enzymes, including matrix metalloproteinases (MMPs)-1, -3, and -13 in addition to cyclooxygenase-2, at both the mRNA and protein levels, whereas FK506BP12 alone did not. In addition, PEP-1-FK506BP12 decreased IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) complex (p38, JNK, and ERK) and the inhibitor kappa B alpha. In the mouse model of carrageenan-induced paw arthritis, PEP-1-FK506BP12 suppressed both carrageenan-induced MMP-13 production and paw inflammation. PEP-1-FK506BP12 may have therapeutic potential in the alleviation of OA progression. [BMB Reports 2015; 48(7): 407-412]

Regulation of HIF-1α stability by lysine methylation

  • Baek, Sung Hee;Kim, Keun Il
    • BMB Reports
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    • v.49 no.5
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    • pp.245-246
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    • 2016
  • The level and activity of critical regulatory proteins in cells are tightly controlled by several tiers of post-translational modifications. HIF-1α is maintained at low levels under normoxia conditions by the collaboration between PHD proteins and the VHL-containing E3 ubiquitin ligase complex. We recently identified a new physiologically relevant mechanism that regulates HIF-1α stability in the nucleus in response to cellular oxygen levels. This mechanism is based on the collaboration between the SET7/9 methyltransferase and the LSD1 demethylase. SET7/9 adds a methyl group to HIF-1α, which triggers degradation of the protein by the ubiquitin-proteasome system, whereas LSD1 removes the methyl group, leading to stabilization of HIF-1α under hypoxia conditions. In cells from knock-in mice with a mutation preventing HIF-1α methylation (Hif1αKA/KA), HIF-1α levels were increased in both normoxic and hypoxic conditions. Hif1αKA/KA knock-in mice displayed increased hematological parameters, such as red blood cell count and hemoglobin concentration. They also displayed pathological phenotypes; retinal and tumor-associated angiogenesis as well as tumor growth were increased in Hif1αKA/KA knock-in mice. Certain human cancer cells exhibit mutations that cause defects in HIF-1α methylation. In summary, this newly identified methylation-based regulation of HIF-1α stability constitutes another layer of regulation that is independent of previously identified mechanisms.

Development of Species-specific Primers for Rapid Detection of Phellinus linteus and P. baumii

  • Kim, Mun-Ok;Kim, Gi-Young;Nam, Byung-Hyouk;Jin, Cheng-Yun;Lee, Ki-Won;Park, Jae-Min;Lee, Sang-Joon;Lee, Jae-Dong
    • Mycobiology
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    • v.33 no.2
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    • pp.104-108
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    • 2005
  • Genus Phellinus taxonomically belongs to Aphyllophorales and some species of this genus have been used as a medicinal ingredients and Indian folk medicines. Especially, P. linteus and morphological-related species are well-known medicinal fungi that have various biological activities such as humoral and cell-mediated, anti-mutagenic, and anti-cancer activities. However, little is known about the rapid detection for complex Phellinus species. Therefore, this study was carried out to develop specific primers for the rapid detection of P. linteus and other related species. Designing the species-specific primers was done based on internal transcribed spacer sequence data. Each primer set detected specifically P. linteus (PL2/PL5R) and P. baumii (PB1/PB4R). These primer sets could be useful for the rapid detection of specific-species among unidentified Phellinus species. Moreover, restriction fragment length polymorphism analysis of the ITS region with HaeIII was also useful for clarifying the relationship between each 5 Phellinus species.

Effect of Interaction between Protocatechualdehyde Produced from Streptomyces lincolnensis M-20 and Copper Ions on Antioxidant and Pro-oxidant Activities (Streptomyces lincolnensis M-20 균주에서 생산된 Protocatechualdehyde와 구리 이온의 상호 작용이 항 산화 및 산화 촉진 활성에 미치는 영향)

  • Kim, Kyoung-Ja;Lee, Jae-Hun;Yang, Yong-Joon
    • Korean Journal of Microbiology
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    • v.50 no.1
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    • pp.22-26
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    • 2014
  • Protocatechualdehyde (PA) is phenolic compound having antioxidative and antitumor activities. PA was purified from supernatant of Streptomyces lincolnensis M-20. In the presence of copper ion, PA acted as pro-oxidant. The antioxidant activity was assessed with the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, and the pro-oxidant effect of PA on DNA damage as pBR322 plasmid DNA-cleaving agents in the presence of Cu(II) ions was investigated. The involvement of reactive oxygen species (ROS) in the DNA damage was confirmed by the inhibition of the DNA breakage by using glutathione (GSH), specific scavenger of ROS. When the increase in ROS reaches a certain level (the toxic threshold), it may trigger cell death. The formation of the PA/Cu(II) chelate complex was confirmed by reaction with ethylenediamine-tetraacetic acid (EDTA), a well-known chelating agent for metal ions, by using UV/Vis spectroscopic analysis.

Spatial Pattern of Copper Phosphate Precipitation Involves in Copper Accumulation and Resistance of Unsaturated Pseudomonas putida CZ1 Biofilm

  • Chen, Guangcun;Lin, Huirong;Chen, Xincai
    • Journal of Microbiology and Biotechnology
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    • v.26 no.12
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    • pp.2116-2126
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    • 2016
  • Bacterial biofilms are spatially structured communities that contain bacterial cells with a wide range of physiological states. The spatial distribution and speciation of copper in unsaturated Pseudomonas putida CZ1 biofilms that accumulated 147.0 mg copper per g dry weight were determined by transmission electron microscopy coupled with energy dispersive X-ray analysis, and micro-X-ray fluorescence microscopy coupled with micro-X-ray absorption near edge structure (micro-XANES) analysis. It was found that copper was mainly precipitated in a $75{\mu}m$ thick layer as copper phosphate in the middle of the biofilm, while there were two living cell layers in the air-biofilm and biofilm-medium interfaces, respectively, distinguished from the copper precipitation layer by two interfaces. The X-ray absorption fine structure analysis of biofilm revealed that species resembling $Cu_3(PO_4)_2$ predominated in biofilm, followed by Cu-Citrate- and Cu-Glutathione-like species. Further analysis by micro-XANES revealed that 94.4% of copper were $Cu_3(PO_4)_2$-like species in the layer next to the air interface, whereas the copper species of the layer next to the medium interface were composed by 75.4% $Cu_3(PO_4)_2$, 10.9% Cu-Citrate-like species, and 11.2% Cu-Glutathione-like species. Thereby, it was suggested that copper was initially acquired by cells in the biofilm-air interface as a citrate complex, and then transported out and bound by out membranes of cells, released from the copper-bound membranes, and finally precipitated with phosphate in the extracellular matrix of the biofilm. These results revealed a clear spatial pattern of copper precipitation in unsaturated biofilm, which was responsible for the high copper tolerance and accumulation of the biofilm.

Numerical Modeling of Tide and Tidal Current in the Kangjin Bay, South Sea, Korea

  • Ro, Young-Jae;Jun, Woong-Sik;Jung, Kwang-Young;Eom, Hyun-Min
    • Ocean Science Journal
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    • v.42 no.3
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    • pp.153-163
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    • 2007
  • This study is based on a series of numerical modeling experiments to understand the tidal circulation in the Kangjin Bay (KB). The tidal circulation in the KB is mostly controlled by the inflow from two channels, Noryang and Daebang which introduce the open ocean water into the northern part of the KB with relatively strong tidal current, while in the southern part of the KB, shallowest region of the entire study area, weak tidal current prevails. The model prediction of the sea level agrees with observed records at skill scores exceeding 90 % in terms of the four major tidal constituents (M2, S2, K1, O1). However, the skill scores for the tidal current show relatively lower values of 87, 99, 59, 23 for the semi-major axes of the constituents, respectively. The tidal ellipse parameters in the KB are such that the semi-major axes of the ellipse for M2 range from 1.7 to 38.5 cm/s and those for S2 range from 0.5 to 14.4 cm/s. The orientations of the major-axes show parallel with the local isobath. The eccentricity values at various grid points of ellipses for M2 and S2 are very low with 0.2 and 0.06 on the average, respectively illustrating that the tidal current in the KB is strongly rectilinear. The magnitude of the tidal residual current speed in the KB is on the order of a few cm/s and its distribution pattern is very complex. One of the most prominent features is found to be the counter-clockwise eddy recirculation cell at the mouth of the Daebang Channel.

Canine nervous-tissue tumors with features of peripheral nerve sheath tumor: histopathological and immunohistochemical findings (말초신경초 종양의 특징을 지닌 개 신경종의 조직병리학적 및 면역조직화학적 진단)

  • Lee, Sun-Gue;Lee, Jae-Ha;Han, Jeong-Hee
    • Korean Journal of Veterinary Service
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    • v.41 no.1
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    • pp.57-61
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    • 2018
  • Canine peripheral nerve sheath tumors (PNSTs) are spindle cell tumors that arise from Schwann cells, perineural cells, fibroblasts or all of them. Based on the morphology and biologic behavior, PNSTs are divided into benign PNST (BPNST) and malignant PNST (MPNST) forms. The aim of this study is to diagnose the two cases of neoplastic tissue samples with features of PNSTs by the histopathology and immunohistochemistry. The study was performed using two specimens from small animal clinic. The first case, A was a mass, 3~4 cm in diameter, extruded from vaginal mucosa of 10-year-old spayed female mixed-breed dog. And the second case, B was a subcutaneous mass, 1.5 cm in diameter, which is originated from right hind leg of 9-year-old castrated male mixed-breed dog. Two cases were stained with hematoxylin and eosin (H&E) for histopathological examination. And also immunohistochemistry (IHC) was performed by the avidin-biotin peroxidase complex (ABC) method with antibodies specific for the following proteins: S-100 protein, smooth muscle actin (SMA) and epidermal growth factor receptor (EGFR). In results, Antoni B schwannoma pattern characterized by pleomorphic, round and fusiform polygonal cells was seen in A. In B, Antoni A pattern, densely packed spindle cells arranged in interlacing bundles was seen in addition to Antoni B pattern. In IHC, cytoplasms of neoplastic cells were diffusely labeled for S-100 expression in A and B. For SMA, both A and B show negative expression. And for EGFR, A shows negative expression but B shows partially positive expression in areas of Antoni B schwannoma pattern. The histopathologic features of two cases coupled with the S-100 immunoreactivity led to a diagnosis of PNST. For SMA, both A and B show negative expression. The diagnosis of A will be a BPNST with the negative result and B will be a MPNST with the positive result for EGFR.