• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.3
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• pp.159-166
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• 2017

Through this study, the authors investigated the anti-steatosis effects of the Amomum cardamomum ethyl acetate fraction in free fatty acids (FFAs)-induced human hepatocellular carcinoma HepG2 cells. The ethyl acetate fraction of Amomum cardamomum (ACEA) was extracted with 70% ethanol and then the extract was evaporated using a rotary evaporator prior to sequential fractionation. Human hepatocellular carcinoma were treated with different concentrations of ACEA in the presence and absence of FFAs. To demonstrate the reactive oxygen species (ROS) scavenging activity, DCFDA level was analyzed by using in vitro assay system. Cell viability, lipid accumulation, intracellular triglycerides, malondialdehyde (MDA), liver steatosis related signaling molecules and inflammatory cytokines such as interleukin (IL)-6, 8, tumor necrosis factor-alpha ($TNF-{\alpha}$) were also investigated. As results, ACEA inhibited the FFAs-induced ROS, lipid accumulation, intracellular triglycerides, and MDA in a dose dependent manner. Treatment of human hepatocellular cells with ACEA induced the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) and carnitine palmitoyltransferase I (CPT1) expression using western blot analysis. ACEA also potently suppressed the FFAs-induced inflammatory cytokines including IL-6, IL-8 and $TNF-{\alpha}$. These results suggest that the ethyl acetate fraction of Amomum cardamoum extract own inhibitory effects of liver steatosis by inhibiting ROS, lipid accumulation, intracellular triglycerides, MDA through AMPK signaling and anti-inflammatory actions.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4161-4168
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• 2015

Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression).

• Journal of the Society of Cosmetic Scientists of Korea
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• v.37 no.4
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• pp.351-356
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• 2011

Citrus unshiu (C. unshiu) Markovich were dried peel of mandarin orange, of which fresh fruit was one of the famous foods in Korea and Eastern Asia. In the oriental medicine, C. unshiu peel was known to have a diuretic effect and to strengthen spleen function. Recently, natural flavonoids of C. unshiu peel have been investigated. In this study, C. unshiu peel extract containing flavonoid-glycosides was cultured with Schizophyllum commune (S. commune) mycelia producing ${\beta}$-glu- cosidase and its biological activities were investigated. ${\beta}$-glucosidase of S. commune mycelia converted the flavonoid-glycosides (rutin and hesperidin) into aglycones (naringenin and hesperetin). Fermented C. unshiu peel extract compounds were analyzed by HPLC system. The photoprotective potential of fermented C. unshiu peel extract was tested in human dermal fibroblasts (HDFs) exposed to UVA. Fermented C. unshiu peel extract extract also showed notable in vitro anti-inflammatory effect on cellular systems generating cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) metabolites. Also, UVB-induced production of interleukin-$1{\alpha}$ in human HaCaT cells was reduced in a dose-dependent manner by treatment with fermented C. unshiu peel extract. These results suggest that fermented C. unshiu peel extract may mitigate the effects of photoaging in skin by reducing UV-induced adverse skin reaction.

• Journal of Periodontal and Implant Science
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• v.52 no.1
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• pp.28-38
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• 2022

Purpose: Macrophages play crucial roles as early responders to bacterial pathogens and promote/ or impede chronic inflammation in various tissues. Periodontal macrophage-induced pyroptosis results in physiological and pathological inflammatory responses. The transcription factor Dec2 is involved in regulating immune function and inflammatory processes. To characterize the potential unknown role of Dec2 in the innate immune system, we sought to elucidate the mechanism that may alleviate macrophage pyroptosis in periodontal inflammation. Methods: Porphyromonas gingivalis lipopolysaccharide (LPS) was used to induce pyroptosis in RAW 264.7 macrophages. Subsequently, we established an LPS-stimulated Dec2 overexpression cellular model in macrophages. Human chronic periodontitis tissues were employed to evaluate potential changes in inflammatory marker expression and pyroptosis. Finally, the effects of Dec2 deficiency on inflammation and pyroptosis were characterized in a P. gingivalis-treated experimental periodontitis Dec2-knockout mouse model. Results: Macrophages treated with LPS revealed significantly increased messenger RNA expression levels of Dec2 and interleukin (IL)-1β. Dec2 overexpression reduced IL-1β expression in macrophages treated with LPS. Overexpression of Dec2 also repressed the cleavage of gasdermin D (GSDMD), and the expression of caspase-11 was concurrently reduced in macrophages treated with LPS. Human chronic periodontitis tissues showed significantly higher gingival inflammation and pyroptosis-related protein expression than non-periodontitis tissues. In vivo, P. gingivalis-challenged mice exhibited a significant augmentation of F4/80, tumor necrosis factor-α, and IL-1β. Dec2 deficiency markedly induced GSDMD expression in the periodontal ligament of P. gingivalis-challenged mice. Conclusions: Our findings indicate that Dec2 deficiency exacerbated P. gingivalis LPS-induced periodontal inflammation and GSDMD-mediated pyroptosis. Collectively, our results present novel insights into the molecular functions of macrophage pyroptosis and document an unforeseen role of Dec2 in pyroptosis.

• Nutrition Research and Practice
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• v.18 no.1
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• pp.19-32
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• 2024

BACKGROUND/OBJECTIVES: Atherosclerosis is associated with increased inflammation in the visceral adipose tissue (VAT). Vitamin D has been reported to modulate the inflammatory responses of stromal vascular cells (SVCs) and adipocytes in adipose tissue, but the role of vitamin D in atherosclerosis biology is unclear. This study examined the effects of in vitro 1,25-dihydroxyvitamin D₃ (1,25[OH]₂D₃) treatment on the inflammatory responses of SVCs and adipocytes from atherosclerotic mice. MATERIALS/METHODS: C57BL/6J (B6) mice were divided randomly into 2 groups and fed a 10% kcal fat control diet (control group, CON) or 41% kcal fat, 0.21% cholesterol (high fat + cholesterol, HFC) diet (obese group, OB), and B6.129S7-Ldlr^tm1Her/J (Ldlr^-/-) mice were fed a HFC diet (obese with atherosclerosis group, OBA) for 16 weeks. SVCs and adipocytes isolated from VAT were pre-incubated with 1,25(OH)₂D₃ for 24 h and stimulated with lipopolysaccarides for the next 24 h. Proinflammatory cytokine production by adipocytes and SVCs, the immune cell population in SVCs, and the expression of the genes involved in the inflammatory signaling pathway in SVCs were determined. RESULTS: The numbers of total macrophages and SVCs per mouse were higher in OB and OBA groups than the CON group. The in vitro 1,25(OH)₂D₃ treatment significantly reduced macrophages/SVCs (%) in the OBA group. Consistent with this change, the production of interleukin-6 and monocyte chemoattractant protein 1 (MCP-1) by SVCs from the OBA group was decreased by 1,25(OH)₂D₃ treatment. The 1,25(OH)₂D₃ treatment significantly reduced the toll-like receptor 4 and dual-specificity protein phosphatase 1 (also known as mitogen-activated protein kinase phosphatase 1) mRNA levels in SVCs and MCP-1 production by adipocytes from all 3 groups. CONCLUSIONS: These findings suggest that vitamin D can attribute to the inhibition of the inflammatory response in VAT from atherosclerotic mice by reducing proinflammatory cytokine production.

• International Journal of Industrial Entomology and Biomaterials
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• v.7 no.2
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• pp.165-173
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• 2003

Cytokines represent an essential part of the innate immune response in mammals. Recently, several studies have reported the presence of cytokine-like activities and molecules in the invertebrates such as echinoderms, tunicates, mollusks and insects. In our serial study, we investigated presence of cytokines in the silkworm, Bombyx mori, infected with several immune inducers. Western blotting analysis using rabbit anti-human cytokines showed the presence of IL-6-like molecule in the hemolymph collected at 8 and 24 hrs after infection with peptidoglycan and oligodeoxynucleotide, and the molecular weight of the proteins was ∼45 kDa. We attempted to isolate the molecule by gel permeation HPLC, anion exchange chromatography, ultra centrifugation, and immuno-dot-blot assay, but until now the effort was not much successful yet. It, however, does not appear that the IL-6-like molecule in the silkworm larvae is a mere experimental artifact happened by Western blotting analysis. Instead, further experiment on this subject probably will provide us more fruitful result as detected in other invertebrates including insects.

• Journal of Sasang Constitutional Medicine
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• v.21 no.1
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• pp.139-149
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• 2009

1. Objectives The roots of Sophora flavescens Aiton (SFA) are widely used as a herbal remedy for allergic inflammation. In this study, we invested the effect of SFA on passive cutaneous anaphylaxis reaction and histamin releas and we demonstrated that SFA suppressed the production of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin- 6 (IL-6), and interleukin -8 (IL-8), through inhibition of the $NF{\kappa}B$, JNK and p38 pathway in the human mast cell line, HMC-1. 2. Methods To accomplish this, we invested passive cutaneous anaphylaxis reaction and histamin release at an animal experiment. In addition, we investigated the effect of SFA on the production of inflammation-related cytokines in HMC-1 cells that were co-treated with PMA and A23187, which can induce production of pro-inflammatory cytokines. 3. Results and Conclusions SFA induced passive cutaneous anaphylaxis reaction and histamin releas and supressed the expression of TNF-${\alpha}$, IL-6, and IL-8. In addition, the protein levels of TNF-${\alpha}$ were also decreased by SFA treatment. Furthermore, SFA inhibited the nuclear translocation of nuclear factor $NF{\kappa}B$ through inhibition of the phosphorylation and degradation of $I{\kappa}B-{\alpha}$, which is an inhibitor of $NF{\kappa}B$. Moreover, SFA also inhibited induction of MAPKs (JNK, p38) and $NF{\kappa}B$ promoter-mediated luciferase activity. Taken together, these results suggest that SFA could be used as a treatment for mast cell-derived allergic inflammatory diseases.

• Journal of Sasang Constitutional Medicine
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• v.13 no.1
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• pp.61-69
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• 2001

사상의학적 견지에서 태음인(太陰人)의 중풍, 치매와 같은 신경계질환에 다용되고 있는 열다한소탕(熱多寒少湯)은 최근에 그 임상적 효과를 뒷받침할 다각적인 연구들이 이루어지고 있음에도 불구하고 그 정확한 약리학적 기전에 대해서는 밝혀지지 않고 있다. 본 연구에서는 인간성상세포를 이용하여 열다한소탕(熱多寒少湯)이 substance P (SP)와 lipopolysaccharide (LPS)에 의해 유도되는 다양한 세포활성물질의 분비량의 조절을 검토함으로써 열다한소탕(熱多寒少湯)의 약리기전을 면역학적 측면에서 보다 세밀하게 살펴보고자 하였다. 열다한소탕(熱多寒少湯) 수침액은 인간 뇌 성상세포로 부터 LPS와 SP의 동시자극에 의해 생성되는 세포활성물질중 interleukin (IL)-1, IL-4, IL-6 및 tumor necrosisfaccor-${\alpha}$ (TNF-${\alpha}$)의 분비를 농도의존적으로 억제했다. 그러나 interferon-${\gamma}$ (IFN-${\gamma}$) 및 IL-2의 분비 조절에는 영향을 미치지 않았다. 그리고 항 IL-$1{\beta}$ 항체에 의해 SP 유도성 TNF-${\alpha}$ 분비의 증가가 억제되기 때문에 IL-1은 TNF-${\alpha}$ 증가를 매개하는 역할을 하는 것으로 사료된다. 이상의 결과는 열다한소탕(熱多寒少湯)에 의한 급성기 중풍환자 치료 효과가 뇌 성상세포로부터 분비되는 세포활성물질의 조절과 밀접한 관련성이 있다는 것을 암시하고 있다.

• Anatomy and Cell Biology
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• v.56 no.2
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• pp.236-251
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• 2023

Alcohol consumption alongside combination antiretroviral therapy (cART) has attracted research interest, especially because of increasing male infertility. This study investigated the combined effects of alcohol and cART on testicular morphology, biomarkers of oxidative stress, inflammation, and apoptosis. Rats, weighing 330-370 g, were divided into four groups of six animals each; control, alcohol treated (A), cART, and alcohol plus cART treated (A+cART). Following 90 days treatment period, animals were euthanized, testis extracted, and routinely processed for histology and immunohistochemical analysis. Significantly decreased epithelial area fraction, increased luminal and connective tissue area fractions, and reduction of epithelial height and spermatocyte number, were recorded in the treated groups compared to control. Extensive seminiferous epithelial lesions including widened intercellular space, karyolysis, and sloughing of germinal epithelium were recorded in all the treated groups. Furthermore, upregulation of inducible nitric oxide synthase and 8-hydroxydeoxyguanosine, interleukin-6, and caspase 3 recorded in treated animals, was more significant in A+cART group. Also, the levels of interleukin-1β and tumor necrosis factor-α were more elevated in A and cART treated groups than in A+cART, while MDA was significantly elevated in cART and A+cART treated groups compared to control group. Altogether, the results indicate testicular toxicity of the treatments. It is concluded that consuming alcohol or cART induces oxidative stress, inflammation, and apoptosis in testis of rats, which lead to testicular structural and functional derangements, which are exacerbated when alcohol and cART are consumed concurrently. The result will invaluably assist clinicians in management of reproductive dysfunctions in male HIV/AIDS-alcoholic patients on cART.

• Food Science and Preservation
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• v.19 no.2
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• pp.287-293
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• 2012

Lycopene, found in tomatoes and tomato products, has antioxidant, anticancer, and anti-inflammatory effects. High-mobility-group box 1 (HMGB1) mediates the pro-inflammatory responses in several inflammatory diseases. In this study, the potential roles of lycopene in the HMGB1-mediated pro-inflammatory gene expressions in the primary human-umbilical-vein endothelial cells (HUVECs) were investigated. The data showed that HMGB1 upregulated the expressions of monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6), secretory phospholipase A2 (sPLA2)-IIA, and prostaglandin E2 (PGE2). Lycopene pre-incubation for 6 h decreased the HMGB1-mediated induction of MCP-1, IL-6, sPLA2-IIA, and PGE2. Further study revealed that the inhibitory effects of lycopene on the HMGB-1 induced expression of pro-inflammatory genes were mediated by the inhibition of two important inflammatory cytokines: tumor necrosis factor (TNF)-${\alpha}$ and nuclear factor (NF)-${\kappa}B$. These results suggest that HMGB1 upregulated the expression of pro-inflammatory genes and lycopene inhibited HMGB-1-induced pro-inflammatory genes by inhibiting TNF-${\alpha}$ and NF-${\kappa}B$. This finding will serve as an important evidence in the development of a new medicine for the treatment of inflammatory diseases.