• The Korean journal of internal medicine
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• 제33권6호
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• pp.1103-1110
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• 2018

Background/Aims: Several epidemiological studies have validated the association of interleukin gene polymorphisms with acute pancreatitis (AP) in different populations. However, there have been few studies in Asian ethnic groups. We aimed to investigate the relationships between inflammatory cytokine polymorphisms and AP as pilot research in a Korean ethnic group. Methods: Patients who had been diagnosed with AP were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. Single-nucleotide polymorphisms (SNPs) of the interleukin $1{\beta}$ (IL1B), interleukin 1 receptor antagonist (IL1RN), and tumor necrosis factor ${\alpha}$ (TNFA) genes of patients with AP were compared to those of normal controls. Results: Between January 2011 and January 2013, a total of 65 subjects were enrolled (40 patients with AP vs. 25 healthy controls). One intronic SNP (IL1RN -1129T>C, rs4251961) was significantly associated with the risk of AP (odds ratio, 0.304; 95% confidence interval, 0.095 to 0.967; p = 0.043). However, in our study, AP was not found to be associated with polymorphisms in the promoter regions of inflammatory cytokine genes, including IL1B (-118C>T, c47+242C>T, +3954C/T, and -598T>C) and TNFA (-1211T>C, -1043C>A, -1037C>T, -488G>A, and -418G>A). Conclusions: IL1RN -1129T>C (rs4251961) genotypes might be associated with a significant increase of AP risk in a Korean ethnic group.

• Journal of Microbiology and Biotechnology
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• 제33권7호
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• pp.864-874
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• 2023

Natural killer (NK) cell dysfunctions against hepatocellular carcinoma (HCC) in a hypoxic environment. Many solid tumors are present in a hypoxic condition, which changes the effector function of various immune cells. The transcription of hypoxic-inducible factors (HIFs) in cancer cells make it possible to adapt to their hypoxic environment and to escape the immune surveillance of NK cells. Recently, the correlation between the transcription of HIF-1α and pro-inflammatory cytokines has been reported. Interleukin (IL)-6 is higher in cancers with a highly invasive ability, and is closely related to the metastasis of cancers. This study showed that the expression of HIF-1α in HCC cells was associated with the presence of IL-6 in the environment of HCC-NK cells. Blocking of IL-6 by antibody in the HCC-NK interaction changed the production of several cytokines including TGF-β, IL-1, IL-18 and IL-21. Interestingly, in a co-culture of HIF-1α-expressed HCC cells and NK cells, blocking of IL-6 increased the production of IL-21 in their supernatants. In addition, the absence of IL-6 significantly enhanced the cytotoxic ability and the expression of the activating receptors (NKG2D, NKp44, and NKG2C) in NK cells to HIF-1α-expressed HCC cells. These effects might be made by the decreased expression of HIF-1α in HCC cells through the inhibited phosphorylation of STAT3. In conclusion, the absence of IL-6 in the interaction of HIF-1α-expressed HCC cells and NK cells could enhance the antitumor activity of NK cells to HCC cells.

• Journal of Microbiology and Biotechnology
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• 제33권10호
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• pp.1281-1291
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• 2023

Infectious diseases caused by drug-resistant Escherichia coli (E. coli) pose a critical concern for medical institutions as they can lead to high morbidity and mortality rates. In this study, amygdalin exhibited anti-inflammatory and antioxidant activities, as well as other potentials. However, whether it could influence the drug-resistant E. coli-infected cells remained unanswered. Amygdalin was therefore tested in a cellular model in which human macrophages were exposed to resistant E. coli. Apoptosis was measured by flow cytometry and the lactate dehydrogenase (LDH) assay. Western immunoblotting and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to quantify interleukin-18 (IL-18), interleukin-1β (IL-1β), and interleukin-6 (IL-6). The production of reactive oxygen species (ROS) in macrophages was detected by ROS kit. The expression of pan-apoptotic proteins in macrophages was measured by qRT-PCR and Western immunoblotting. Drug-Resistant E. coli inhibited cell viability and enhanced apoptosis in the cellular model. In cells treated with amygdalin, this compound can inhibit cell apoptosis and reduce the expression of pro - inflammatory cytokines such as IL-1β, IL-18 and IL-6. Additionally, it decreases the production of PANoptosis proteins, Furthermore, amygdalin lowered the levels of reactive oxygen species induced by drug-resistant E. coli, in cells, demonstrating its antioxidant effects. Amygdalin, a drug with a protective role, alleviated cell damage caused by drug-resistant E. coli in human macrophages by inhibiting the PANoptosis signaling pathway.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2002년도 학술대회지
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• pp.288-297
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• 2002

In this paper, we present evidence that the red ginseng from Panax ginseng C.A. Meyer inhibits the recurrence of advanced gastric cancer and shows immunomodulatory activities during postoperative chemotherapy. Flow cytometric analyses for peripheral T-lymphocyte subsets showed that the red ginseng powder restored CD4 levels to the initial preoperative values during postoperative chemotherapy. Depression of CD3 during postoperative chemotherapy was also inhibited by the red ginseng powder ingestion. This study demonstrated a 5-year disease free survival and overall survival rate that was significantly higher in patients taking the red ginseng powder during postoperative chemotherapy vs. control $(68.2\%\;vs.\;33.3\%,\;76.4\%\;vs.\;38.5\%,$ respectively, p<0.05). The mean value of serum IL-10 of the ginseng group was reduced progressively during the postoperative chemotherapy. The values of the ginseng group were close to that of the control group on postoperative months 3. These studies suggest that the red ginseng may have some immunomodulatory properties associated with CD3 and CD4 activity and interleukin 10 during postoperative chemotherapy and some potential of improving prognosis in patients with advanced gastric cancer.

• Toxicological Research
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• 제33권4호
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• pp.325-332
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• 2017

3-Bromo-4,5-dihydroxybenzaldehyde (BDB) is a natural bromophenol compound that is most commonly isolated from red algae. The present study was designed to investigate the anti-inflammatory properties of BDB on atopic dermatitis (AD) in mice induced by 2,4-dinitrochlorobenzene (DNCB) and on lipopolysaccharide (LPS)-stimulated murine macrophages. BDB treatment (100 mg/kg) resulted in suppression of the development of AD symptoms compared with the control treatment (induction-only), as demonstrated by reduced immunoglobulin E levels in serum, smaller lymph nodes with reduced thickness and length, a decrease in ear edema, and reduced levels of inflammatory cell infiltration in the ears. In RAW 264.7 murine macrophages, BDB (12.5, 25, 50, and $100{\mu}M$) suppressed the production of interleukin-6, a proinflammatory cytokine, in a dose-dependent manner. BDB also had an inhibitory effect on the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) and signal transducer and activator of transcription 1 (STAT1; Tyr 701), two major signaling molecules involved in cellular inflammation. Taken together, the results show that BDB treatment alleviates inflammatory responses in an atopic dermatitis mouse model and RAW 264.7 macrophages. These results suggest that BDB may be a useful therapeutic strategy for treating conditions involving allergic inflammation such as atopic dermatitis.

• 동의신경정신과학회지
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• 제33권3호
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• pp.277-285
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• 2022

Objectives: Gastrodia elata (GE) has been used to treat cognition impairment, including Alzheimer's disease (AD) in Korea. The purpose of this study was to investigate the effects of GE water extracts (GEE) on the lipopolysaccharide (LPS)-induced AD model in mice. (Aβ). Methods: We classified six groups as follow; group 1: control (CON), group 2: LPS (0.5 mg/kg/day, four times), group 3: 4 mg/kg donepezil (DP), group 4: 100 mg/kg GEE+LPS, group 5: 200 mg/kg GEE+LPS, group 6: 500 mg/kg GEE+LPS. Results: We found that GEE has an effect that inhibits decrease of discrimination index in object recognition test, as well as spontaneous alteration in the Y-maze test by LPS. Treatment with LPS increased amlyloid-β (Aβ) concentration, and decreased brain-derived neurotrophic factor (BDNF) in cerebral cortex of mice. However, GEE significantly protected against LPS-induced Aβ and BDNF changes. Our findings also showed that the inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β)] mRNA and protein were up-regulated by the LPS injection. But GEE significantly suppressed LPS-induced inflammatory cytokines increase in a dose-dependent manner. Conclusions: This study suggests that the GEE may be an effective AD therapeutic agent, in treating neurodegenerative diseases including AD.

• 대한본초학회지
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• 제22권2호
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• pp.25-33
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• 2007

Objectives : Oriental pear was used as treatment of asthma, control of blood pressure, diabetes in oriental medicine. The aim of this study was to observe the effects of Phenolic compound extracted from pear and herbal drugs to treat asthma. Methods : In order to study the effect of oral administration of phenolic compound extracted from pear and herbal drugs(Platycodon grandiflorum, Prunus armeniaca) on allergic asthma, mice were pre-treated by oral administration of the solution before antigen sensitization four times for 8 days. 2 days later, mice were actively sensitized with a subcutaneous injection of ovalbumin and 13 days later, they were provoked with ovalbumin aerosols. The animals were divided into four groups; Saline, orally administered saline. PC-A, orally administered Phenolic compound extracted from pear peel 10mg/kg/ml. PC-B, orally administered Phenolic compound extracted from pear peel and flesh 10mg/kg/ml. PC-C, orally administered pear 10m/kg/ml, Platycodon grandiflorum 24.4 mg/kg/ml and Prunus armeniaca 33.3 mg/kg/ml. Serum level of IgE, IL-4, cell numbers in the bronchoalveolar lavage fluid(BALF), and in vitro isometric contractile responses of the isolated tracheal smooth muscle(TSM) to acetylcholine(ACh, $0.1-1000{\mu}M$), KCl were measured. Results : Contractile responses of TSM to ACh were decreased in PC-A group at Ach 0.1, 0.3, 1 ${\mu}M$, decreased in PC-B at 0.1 ${\mu}M$ and decreased in PC-C at 0.1, 0.3, 1, 10, 30 ${\mu}M$. The maximal contractile response of TSM to KCl was decreased in PC-C group, The cell numbers of eosinophil in BALF were decreased in PC-C group, and those of macrophages in BALF were decreased in PC-A and PC-C group. Interleukin-4 in BALF was decreased in PC-A, PC-B, PC-C group. Conclusion : Based on the above results it is assumed that oral administration of phenolic compound extracted from pear and herbal drugs can help the treatment of deficiency allergic Asthma.

• Annals of dermatology
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• 제30권6호
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• pp.653-661
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• 2018

Background: Citron is well known for an abundance of antioxidative and anti-inflammatory ingredients such as vitamin C, polyphenol compounds, flavonoids, and limonoids. Objective: In this study, we aimed to evaluate the effects of citron essential oils on rosacea mediators in activated keratinocytes in vitro. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with $1{\alpha}$, 25-dihydroxyvitamin $D_3$ ($VD_3$) and interleukin 33 (IL-33) with LL-37 to induce rosacea mediators such as kallikrein 5 (KLK5), cathelicidin, vascular endothelial growth factor (VEGF), and transient receptor potential vanilloid 1 (TRPV1). These mediators were analyzed by performing reverse-transcription polymerase chain reaction (PCR), quantitative real-time PCR, immunocytofluorescence and enzyme-linked immunosorbent assay after NHEKs were treated with citron seed and unripe citron essential oils. Results: The messenger RNA (mRNA) and protein levels of KLK5 and LL-37 induced by $VD_3$ were suppressed by citron seed and unripe citron essential oils. Furthermore, the mRNA and protein levels of VEGF and TRPV1 induced by IL-33 with LL-37 were also suppressed by citron essential oils. Conclusion: These results show that citron essential oils have suppressive effects on rosacea mediators in activated epidermal keratinocytes, which indicates that the citron essential oils may be valuable adjuvant therapeutic agents for rosacea.

• Clinical and Experimental Pediatrics
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• 제52권2호
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• pp.234-241
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• 2009

목 적 : 가와사끼병에서 갑상샘 호르몬과 혈청 TNF-${\alpha}$, IL-6 및 NT-proBNP 농도와의 연관성을 알아보고자 하였다. 방 법 : 환자군으로 가와사끼병 환아 52명과 대조군으로 다른 열성 질환 환아 10명을 대상으로 하였다. 환자군의 치료 전 급성기와 치료 3-9일 후의 아급성기 때의 혈청과 대조군의 급성 발열기 혈청에서 갑상샘 호르몬과 TNF-${\alpha}$, IL-6, NT-proBNP를 각각 측정하여 비교하였다. 환자군에서는 심장 초음파검사로 관상동맥 병변의 유무를 조사하였다. 결 과 : 가와사끼병의 63.5%에서 저 $T_3$ 증후군($T_3$<100 ng/dL)이 동반되었다. 급성 가와사끼병의 $T_3$는 대조군에 비해 유의하게 낮았다($86.8{\pm}36.6$ vs $116.7{\pm}24.4$ ng/dL, P<0.05). 가와사끼병 환자군에서 $T_3$는 급성기에 감소하고 갑상샘 호르몬의 치료없이 아급성기에 증가하였으나($84.3{\pm}33.0$ vs $109.3{\pm}37.5$ ng/dL, P<0.01), 반대로 TNF-${\alpha}$, IL-6 및 NT-proBNP는 모두 급성기에 증가하고 아급성기에 감소하였다. 가와사끼병 환자군에서 저 $T_3$군(n=33)은 정상 $T_3$군(n=19)에 비해 신장 및 간기능의 차이는 없었고, NT-proBNP는 높았으며, IL-6는 약간 높은 경향을 보였다. 또한 $T_3$는 IL-6 (r=-0.12, P>0.05) 및 NT-proBNP(r=-0.54, P<0.001)와 반비례 관계를 보였다. 관상동맥 병변을 보인 가와사끼병 환아 4명 중 3명에서 $T_3$가 25.0-42.7 ng/dL로 매우 감소하였다. 면역글로불린 치료반응군(n=45)에 비해 저항군(n=7)에서 $T_3$는 더 낮았고($93.8{\pm}33.5$ vs $41.6{\pm}19.8$ ng/dL, P<0.001), IL-6와 NT-proBNP는 더 높았다. 결 론 : $T_3$는 가와사끼병의 급성기에 감소되며 아급성기에 갑상샘 호르몬의 치료 없이 정상화된다. $T_3$ 감소는 부분적으로 TNF-${\alpha}$ 보다는 IL-6의 작용에 의해 유발되며 NT-proBNP의 상승과 연관된다. 가와사끼병에서 $T_3$ 측정은 다른 열성 질환과의 감별진단에, 질병경과를 모니터하는데, 심근 손상의 초기 표식자로, 질병의 심한 정도를 예측하는데 이용할 수 있으리라 생각된다.

• 대한치과교정학회지
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• 제33권3호
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• pp.199-210
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• 2003

치아이동 시 발생하는 골흡수에서 이미 여러 cytokine의 중요성이 강조된 바 있으며 이 가운데 interleukin-6는 구강 및 연골조직 등에서 많은 연구의 초점이 되어 왔으나 확실한 기전은 아직까지 정확히 확립되어 있지 못하다 골흡수 시 조골세포에서 유리되는 interleukin-6 (IL-6)와 nitric oxide (NO) 등이 골흡수의 조절자로 최근 대두되고 있으며 Mitogen-activated Protein kinase (MAPK)의 활성화로 인해 염증성 cytokine등이 유리될 수 있음이 최근 macrophage 등에서 증명된 바 있다. 그러므로 치아이동을 비롯한 구강 내 여러 염증의 조건에서 골흡수의 대표인자인 IL-6및 NO유리가 MAPK등의 활성 등을 통해 조절될 수 있는 가능성을 시사하고 있다. 본 연구에서 조골세포 특징을 대부분 가지고 있는 조골세포주 MC3T3El에서 p-38 MAP kinase을 매개로 NO와 IL-6가 유리됨을 확인하고자 하였다. $10\%$ Fetal Bovine Serum이 첨가된 -MEM 배양액으로 배양한 조골세포주인 MC3T3El 세포에 tumor necrosis $factor-\alpha(TNF-\alpha)$, $interferon-\gamma(IFN-\gamma)$ 및 lipopolysacchalide(LPS) 등의 단독처리 시 NO와 IL-6의 증가는 확인되지 않았으나 $TNF-\alpha/IFN-\gamma$ 혹은 $LPS/IFN-\gamma$ 등의 처치시 NO와 IL-6의 유의한 증가를 보였으며, NO발현에 직접 관여하는 inducible nitric oxide synthase (iNOS)와 IL-6 단백질 및 mRNA의 발현을 관찰하였다. 또한 specific p-38 MAP kinase inhibitor인 SB203580의 NO와 IL-6의 생성 억제를 관찰하고 단백질과 mRNA발현억제를 통해서도 확인함으로써 SB203580은 transcription 단계에서 NO와 IL-6의 생성을 조절하고 있음을 시사하여 주고 있다. $TNF-\alpha/IFN-\gamma$ 혹은 $LPS/IFN-\gamma$ 처치 시 p-38 MAP Kinase의 활성을 관찰하였으나 단독 처치 시 역시 P-38 MAP Kinase의 활성을 확인함으로써 NO와 IL-6생성기전에는 p-38 MAP Kinase이외에 다른 인자 역시 관여하고 있음을 보여주고 있다. 본 연구에서는 치아 등의 골조직의 구성 세포인 조골세포에서 NO와 IL-6유리를 확인하였으며, 또한 이들의 생성기전중의 하나로 p-38 MAP Kinase가 transcription 단계에서 관여하고 있음을 확인하였다.