• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.2
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• pp.113-119
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• 2019

During tumor progression various immunosuppressive cells are recruited to a tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are particularly abundant in TME. Based on their function, macrophages are categorized into two phenotypes: tumoricidal M1 and tumor-supportive M2. Generally, TAMs closely resemble M2-macrophages and lead to tumor growth. However, their phenotype can be changed by immune activator from M2 to M1 and thus promote tumor immunotherapy. Ginseng extracts are well known for its anti-tumor and anti-inflammatory effects from numerous reported studies. However, the mechanism of their effects is still not clear. Recently, some studies suggested that ginseng extracts induced immune activation as well as anti-tumor activities by a repolarization of activated macrophage from M2 phenotype to M1 phenotype. But, further verification about the mechanism as to how ginseng extracts can stimulate the immune response is still needed. In this study, we investigated whether ginseng extracts can alter the phenotype from M2 macrophages to M1 macrophages in mice by using a radiolabeled liposome. And we also evaluated the potential of radiolabeled liposome as a nuclear imaging agent to monitor the transition of phenotype of TAMs. In conclusion, the ginseng extracts seem to change the phenotype of macrophages from M2 to M1 like as lipopolysaccharide (LPS) in mice.

• Journal of Pharmacopuncture
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• v.22 no.4
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• pp.253-259
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• 2019

Objectives: It is reported that tumor-associated macrophages (TAMs) contribute to cancer progression by promoting tumor growth and metastasis. The purpose of this study is to investigate the effect of different fractions of Adenophora triphylla var. japonica (AT) on the polarization of macrophages into the M2 phenotype, a major phenotype of TAMs. Methods: We isolated hexane, ethyl acetate, and butanol fractions from crude ethanol extract of AT. The cytotoxicity of AT in RAW264.7 cells was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RAW264.7 cells were polarized into the M2 phenotype by treatment with interleukin (IL)-4 and IL-13. The expression of M2 macrophage marker genes was detected by reverse transcription polymerase chain reaction (RT-PCR). The phosphorylation level of signal transducer and activator of transcription 6 (STAT6) was investigated by western blot analysis. The migration of Lewis lung carcinoma (LLC) cells was examined by transwell migration assay using conditioned media (CM) collected from RAW264.7 cells as a chemoattractant. Results: Among various fractions of AT, the ethyl acetate fraction of AT (EAT) showed the most significant suppressive effect on the mRNA expression of M2 macrophage markers, including arginase-1, interleukin (IL)-10 and mannose receptor C type 1 (MRC-1), up-regulated by treatment of IL-4 and IL-13. In addition, EAT suppressed the phosphorylation of STAT6, a critical regulator of IL-4 and IL-13-induced M2 macrophage polarization. Finally, the increased migration of Lewis lung carcinoma (LLC) cells by CM from M2-polarized RAW264.7 cells was reduced by CM from RAW264.7 cells co-treated with EAT and M2 polarization inducers. Conclusion: We demonstrated that EAT attenuated cancer cell migration through suppression of macrophage polarization toward the M2 phenotype. Additional preclinical or clinical researches are needed to evaluate its regulatory effects on macrophage polarization and anti-cancer activities.

• Journal of Microbiology and Biotechnology
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• v.1 no.3
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• pp.169-175
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• 1991

Pediococcus acidilactici strain M produced a bacteriocin which was proteinaceous, heat stable, and exhibited antimicrobial activity against lactic acid bacteria, variety of food spoilage and pathogenic bacteria. The antimicrobial activity was not caused by $H_2$$O_2$ and organic acid, and was remained between pHs of 4.0 to 9. Molecular weight of crude bacteriocin was approximately 2, 500. Phenotypic assignment after plasmid cruing experiment demonstrated that a 53.7 kilobase (kb) plasmid, designated as pSUC53, was responsible for the sucrose fermentation phenotype ($Suc^+$) and a 11.1 kb plasmid, designated as pBAC11, was associated with bacteriocin production phenotype ($Bac^+$). Neither of the two plasmids were linked to antibiotic resistance.

• Journal of Microbiology
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• v.39 no.3
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• pp.236-239
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• 2001

Group A Streptococcus strain ST4529 is a provisional new ems type which has been recently reported in Malaysia (Jomal, et al. 1999. Energ. Infect . Dis. 5,10-14). This strain was found to be opacity factor (OF) negative with a Tl phenotype. Usually, OF negative strains with T1 phenotypes are associated with acute rheumatic fever. However, strain ST4529 was isolated from the blood of a patient with septicemia. Comparison of the deduced amino acid sequence of the mature hypervariable N-terminus of ST4529 showed only 43% identity with that of M5, the closest matched OF negative strain with a T1 phenotype. Thus, ST4529 most probably encodes a new serospecifically unique M protein which is associated with septicemia rather than pharyngitis infections. The strains with these phenotypes are very important because their sequences should be considered for developing any anti-streptococcal vaccines.

• Journal of Life Science
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• v.30 no.2
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• pp.113-121
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• 2020

Macrophages are initiators for regulating a host's defenses to eliminate pathogens and trigger tissue repair. Macrophages are classified into two types: classically (M1) activated macrophages and alternatively (M2) activated macrophages. M1-phenotype macrophages directly or indirectly kill infectious organisms and tumor cells via pro-inflammatory responses, whereas M2-phenotype macrophages remodel wounded tissue through anti-inflammatory responses. In this paper, we investigated how Phellinus linteus hot water extract passed from Diaion HP-20 resin (PLEP) regulates polarization of M1-like or M2-like macrophages in human THP-1 cells. PLEP did not have cytotoxicity at a high concentration of 300 ㎍/ml. We observed morphological alteration of the THP-1 cells, which are stimulated by PLEP, LPS/INF-γ (M1 stimulators) or IL-4/IL13 (M2 stimulators). PLEP exposure induced morphology contiguous with LPS/INF-γ. qPCR was also performed to determine whether PLEP influences M1 or M2 polarization-related genes. M1-phenotype macrophage-specific genes, such as TNF-α, IL-1β, IL-6, IL-8, CXCL10 and CCR7, were enhanced by PLEP in a dose-dependent manner similar to LPS/INF-γ. Conversely, M2-phenotype-specific genes, such as MRC-1, DC-SIGN, CCL17 and CCL22, were suppressed by PLEP. PLEP also significantly up-regulated secretory inflammation cytokines related to M1 polarization of macrophages, including TNFα, IL-1β and IL-6, which was similar to the gene expression. Further, MAPK and NF-κB signaling were increased by treatment with PLEP, resulting in enhancement of cytokine secretion. PLEP might therefore be used as a promising booster of pro-inflammatory responses through M1 polarization of human THP-1 cells.

• Journal of Periodontal and Implant Science
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• v.29 no.3
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• pp.655-664
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• 1999

본 논문은 조기발병형 치주염에 이환된 환자의 immunoglobulin allotype markers(Gm)에 대한 연구를 한 것이다. 원래 이전의 논문에서 Porphyromonas gingivalis(Pg)에 대한 항체 역가를 측정하기위해 선택되었던 환자로 이는 subform I(distinctive localized juvenile periodontitis(LIP) pattern)으로부터 3명, subtype II(post-LJP pattern)으로부터 19명, subform III(localized but rapidly progressing pattern)으로부터 15명 그리고 subform Ⅳ(distinctive rapidly pregressing periodontitis(RPP)으로부터 24명을 추출하여 구성하였고, 각각 인종과 나이에 맞게 50명의 대조군을 구성했다. Gm type은 hemagglutination inhibition assay; b0b1b3b5, G3m(s), G3m(t)를 포함한 G1m(a), G1m(x), G1m(f), G2m(n), G3m(g), G3m(b)로 확인했었다. 관찰되어진 Gm haplotypes의 도수는 각각의 EOP subform에 따라 계산되었고 Gm phenotype은 각 환자에서 발견된 증가된 IgG subclass responses의 다양성에 따라 구분했다. 환자들 중에서 관찰된 9개의 Gm phenotype 은 4개의 Gm haplotype으로 나타났다. subform Ⅳ에서 관찰되어진 모든 4개의 Gm haplotype의 도수는 대조군과 유의성있는 차이가 났다. 특히 haplotype afnb(Gm(n))의 그것이 유의성있게 높았다. 더욱이 G2m(n)은 IgG4와 IgG1의 level뿐만 아니라 IgG2 level의 증가와 밀접한 관련이 있었다. Gm phenotype을 검사 할 때 IgG1+2와 IgG1+2+4모두에서 antibody level이 증가한 모든 환자가 일관되게 Gm phenotype agfnb나 axfnb를 가졌다. 결론적으로, IgG subclass response는 개인의 immunogenetic marker에 의해 조절되었고 genetic predisposition의 가능성은 EOP subform IV환자에서 관찰할 수 있었다. 더욱이 G2m(n)과 Gm phenotype agfnb나 axfnb 모두 IgG1+2 나 IgG1+2+4 antibody의 증가와 밀접한 관련이 있었다.

• Journal of Microbiology
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• v.35 no.3
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• pp.228-233
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• 1997

The MTF1 gene of Saccharomyces cerevisiae encodes a 43 kDa MITOCHONDRIAL RNA polymerase specificity factor which recognizes mitochondrial promoters to initiate correct transcription. To better understand structure-function of the MTF1 gene as well as the transcription mechanism of mitochondrial RNA polymerase, two cold-sensitive alleles of the MTF1 mutation were isolated by plasmid shuffling method after PCR-based random mutagenesis of the MTF1 gene. The mutation sites were analyzed by nucleotide sequencing. These cs phenotype mtf1 mutants were respiration competent on the nonfermentible glycerol medium at the permissive temperature, but incompetent at 13.deg.C. The cs phenotype allele of the MTF1, yJH147, encoded an L146P replacement. The other cs allele, yJH148, contained K179E and K214M double replacements. Mutations in both alleles were in a region of Mtflp which is located between domains with amino acid sequence similarities to conserved regions 2 and 3 of bacterial s factors.

• Nutrition Research and Practice
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• v.10 no.6
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• pp.623-628
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• 2016

BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype. MATERIALS/METHODS: Male C57BL/6 mice were fed a regular diet (RD), high-fat diet (HFD), or HFD supplemented with quercetin (HF+Que, 0.5g/kg diet) for nine weeks. Inflammatory cytokines and macrophage markers were measured by ELISA and RT-PCR, respectively. HO-1 protein was measured by Western blotting. RESULTS: Quercetin supplementation decreased levels of inflammatory cytokines ($TNF{\alpha}$, IL-6) and increased that of the anti-inflammatory cytokine (IL-10) in the livers of HFD-fed mice. This was accompanied by upregulation of M2 macrophage marker genes (Arg-1, Mrc1) and downregulation of M1 macrophage marker genes ($TNF{\alpha}$, NOS2). In co-cultures of lipid-laden hepatocytes and macrophages, treatment with quercetin induced HO-1 in the macrophages, markedly suppressed expression of M1 macrophage marker genes, and reduced release of MCP-1. Moreover, these effects of quercetin were blunted by an HO-1 inhibitor and deficiency of nuclear factor E2-related factor 2 (Nrf2) in macrophages. CONCLUSIONS: Quercetin reduces obesity-induced hepatic inflammation by promoting macrophage phenotype switching. The beneficial effect of quercetin is associated with Nrf2-mediated HO-1 induction. Quercetin may be a useful dietary factor for protecting against obesity-induced steatohepatitis.

• International Journal of Molecular Medicine
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• v.43 no.5
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• pp.2177-2186
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• 2019

The epidemiological, animal and cell effects of plant metabolites suggest versatile health benefits of flavonoids. However, whether flavonoids affect the deleterious biological activity of oxygenated cholesterol molecules remains to be elucidated. The present study investigated the effects of 4'-O-methylalpinumisoflavone (mAI) isolated from Maclura tricuspidata (Cudrania tricuspidata) on the 27-hydroxycholesterol (27OHChol)-induced activation of monocytes/macrophages using human THP-1 cells. mAI dose-dependently impaired the expression of C-C motif chemokine ligand (CCL)2 chemokine and the migration of monocytic cells enhanced by 27OHChol. mAI downregulated the surface and cellular levels of CD14 and inhibited the release of soluble CD14. This isoflavone significantly weakened the lipopolysaccharide responses that were enhanced in the presence of 27OHChol, and inhibited the transcription and secretion of the active gene product of matrix metalloproteinase-9. mAI also suppressed the expression of C-C motif chemokine receptor 5 ligands, including CL3 and CCL4, and M1-phenotype markers induced by 27OHChol. Furthermore, mAI impaired phosphorylation of the nuclear factor-κB p65 subunit without affecting the phosphorylation of Akt. These results indicate that mAI inhibits the activation of monocytes/macrophages to the immunostimulatory phenotype in a milieu rich in 27OHChol, suggesting potential benefits of the flavonoid for the treatment of diseases in which the pathogenesis is linked to 27OHChol-induced inflammatory responses.

• BMB Reports
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• v.50 no.1
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• pp.31-36
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• 2017

High-dose caffeine uptake is a developmental stressor and causes food-avoidance behavior (aversion phenotype) in C. elegans, but its mode of action is largely unknown. In this study, we investigated the molecular basis of the caffeine-induced aversion behavior in C. elegans. We found that aversion phenotype induced by 30 mM caffeine was mediated by JNK/MAPK pathway, serotonergic and dopaminergic neuroendocrine signals. In this process, the dopaminergic signaling appears to be the major pathway because the reduced aversion behavior in cat-2 mutants and mutants of JNK/MAPK pathway genes was significantly recovered by pretreatment with dopamine. RNAi depletion of hsp-16.2, a cytosolic chaperone, and cyp-35A family reduced the aversion phenotype, which was further reduced in cat-2 mutants, suggesting that dopaminergic signal is indeed dominantly required for the caffeine-induced food aversion. Our findings suggest that aversion behavior is a defense mechanism for worms to survive under the high-dose caffeine conditions.