• Title/Summary/Keyword: Lung cells

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SARS-CoV-2 Infection Induces HMGB1 Secretion Through Post-Translational Modification and PANoptosis

  • Man Sup Kwak;Seoyeon Choi;Jiseon Kim;Hoojung Lee;In Ho Park;Jooyeon Oh;Duong Ngoc Mai;Nam-Hyuk Cho;Ki Taek Nam;Jeon-Soo Shin
    • IMMUNE NETWORK
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    • v.23 no.3
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    • pp.25.1-25.17
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    • 2023
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage and mortality. High-mobility group box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by pro-inflammatory stimuli, including viral infections, and its excessive secretion levels are related to a variety of inflammatory diseases. Here, the aim of the study was to show that SARS-CoV-2 infection induced HMGB1 secretion via active and passive release. Active HMGB1 secretion was mediated by post-translational modifications, such as acetylation, phosphorylation, and oxidation in HEK293E/ACE2-C-GFP and Calu-3 cells during SARS-CoV-2 infection. Passive release of HMGB1 has been linked to various types of cell death; however, we demonstrated for the first time that PANoptosis, which integrates other cell death pathways, including pyroptosis, apoptosis, and necroptosis, is related to passive HMGB1 release during SARS-CoV-2 infection. In addition, cytoplasmic translocation and extracellular secretion or release of HMGB1 were confirmed via immunohistochemistry and immunofluorescence in the lung tissues of humans and angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.

Antioxidant and anticancer activities of Adenophora triphylla leaf and root extracts (새싹 잔대 잎과 뿌리의 항산화 및 항암 효과)

  • Seon Young Yoon;Ki Hyun Kim;Tae Kyung Hyun
    • Journal of Plant Biotechnology
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    • v.50
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    • pp.137-141
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    • 2023
  • The root of Adenophora triphylla is a highly valued medicinal resource that is used to prevent human obesity, cancer, and inflammation, whereas young leaves or sprouts of A. triphylla are used as food ingredients. In this study, we compared the antioxidant and anticancer activities of 70% ethanol extracts of A. triphylla roots and leaves. The leaf extract exhibited stronger 2,2-diphenyl-1-picrylhydrazyl (DPPH)-radical scavenging activity, reducing power, and oxygen radical absorbance capacity (ORAC) than the root extract. Furthermore, the leaf extract was observed to be a potent source of anticancer compounds that were effective against A549 (lung cancer), LNcaP (prostate cancer), SKOV3 (ovarian cancer), and Caco-2 (colorectal cancer) cells. These results indicate that not only the roots but also the leaves of A. triphylla can serve as valuable sources of functional materials in the pharmaceutical industry.

Umami taste receptor suppresses cancer cachexia by regulating skeletal muscle atrophy in vivo and in vitro

  • Sumin Lee;Yoonha Choi;Yerin Kim;Yeon Kyung Cha;Tai Hyun Park;Yuri Kim
    • Nutrition Research and Practice
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    • v.18 no.4
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    • pp.451-463
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    • 2024
  • BACKGROUND/OBJECTIVES: The umami taste receptor (TAS1R1/TAS1R3) is endogenously expressed in skeletal muscle and is involved in myogenesis; however, there is a lack of evidence about whether the expression of the umami taste receptor is involved in muscular diseases. This study aimed to elucidate the effects of the umami taste receptor and its mechanism on muscle wasting in cancer cachexia using in vivo and in vitro models. MATERIALS/METHODS: The Lewis lung carcinoma-induced cancer cachexia model was used in vivo and in vitro, and the expressions of umami taste receptor and muscle atrophy-related markers, muscle atrophy F-box protein, and muscle RING-finger protein-1 were analyzed. RESULTS: Results showed that TAS1R1 was significantly downregulated in vivo and in vitro under the muscle wasting condition. Moreover, overexpression of TAS1R1 in vitro in the human primary cell model protected the cells from muscle atrophy, and knockdown of TAS1R1 using siRNA exacerbated muscle atrophy. CONCLUSION: Taken together, the umami taste receptor exerts protective effects on muscle-wasting conditions by restoring dysregulated muscle atrophy in cancer cachexia. In conclusion, this result provided evidence that the umami taste receptor exerts a therapeutic anti-cancer cachexia effect by restoring muscle atrophy.

Role of Protease Activated Receptor 2 (PAR2) in Aspergillus Protease Allergen Induces Th2 Related Airway Inflammatory Response (Aspergillus 단백분해효소 알러젠에 의해 유도된 Th2 관련 기도염증반응에서 protease activated receptor 2 (PAR2)의 역할)

  • Yu, Hak-Sun
    • Journal of Life Science
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    • v.20 no.4
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    • pp.503-510
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    • 2010
  • Most allergens have protease activities, suggesting that proteases may be a key link between Th2-type immune reactions in allergic responses. Protease activated receptor (PAR) 2 is activated via the proteolytic cleavage of its N-terminal domain by proteinases. To know the role of PAR2 in Aspergillus protease allergen activated Th2 immune responses in airway epithelial cells, we investigated and compared immune cell recruitment and level of chemokines and cytokines between PAR2 knock out (KO) mice and wild type (WT) mice. There were evident immune cell infiltrations into the bronchial alveolar lavage fluid (BALF) of WT mice, but the infiltrations in PAR2 KO mice were significantly lowered than those of WT mice. The IL-25, TSLP, and eotaxin gene expressions were profoundly increased after Aspergillus protease, but their expression was significantly lowered in PAR2 KO mice in this study. Compared to PAR2 KO mice, OVA specific IgE concentrations in serum of WT mice were quite increased; moreover, the IgE level of PAR2 KO mice was lower than in WT mice. The IL-25 expression by Aspergillus protease stimulation was significantly reduced by p38 specific inhibitor treatment. In this study, we determined that Th2 response was initiated with IL-25 and TSLP mRNA up-regulation in lung epithelial cells via PAR2 after Aspergillus protease allergen treatment.

Screening of Anticancer and Immune Activities by the Extracts of Fatsia japonica Decne. et Planch. (팔손이 용매별 추출물의 항암 및 면역 활성 탐색)

  • Kim, Dae-Ho;Kim, Jung-Hwa;You, Jin-Hyun;Kim, Cheol-Hee;Kwon, Min-Chul;Lee, Hak-Ju;Hwang, Baik;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.13 no.3
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    • pp.87-92
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    • 2005
  • The study was performed using of ethanol and water extracts of Fatsia japonica Decne. et Planch. in anticancer and immune activities. All extracts of 1.0 $g/{\ell}$ concentration were increased in over 60% of the anticancer activites in A549 and MCF7 cells. Root barks inhibited 55%, 74% in A549 and MCF7 cell by adding ethanol extracts of $g/{\ell}$ concentration. The cytotoxicity of human lung nomal cell (HEL299) counted up to about 22% for ethanol extracts of root barks in 1 $g/{\ell}$ concentration. The activity of human immune T and B cells were increased up to $140{\sim}170%$ by adding ethanol extract of the root barks. Increasing trend of secretion of cytokine (IL-6, $TNF-{\alpha}$) from human B and T cell for 5 days cultivation has been abserved. From the results, the anticancer and immune-stimulatory activities of the roots extract were higher than the extracts of other parts.

Isolation of Cucurbitacin E from Sprouted Pumpkin Seed and Analysis of Its Anti-cancer and Anti-inflammatory Activities (발아 호박씨로부터 Cucurbitacin E의 분리정제 및 항암, 항염증 활성)

  • Sim, Hu-Sung;Jang, Byeong-Chur;Park, Hye-Min;Jeng, Byeong-Yong;Oh, Man-Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.7
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    • pp.834-840
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    • 2008
  • In order to improve the use of pumpkin seed, the present study was performed to isolate compositions of the bitter components which were not seen in pumpkin seed itself but newly biosynthesized during germination of the seed. The compositions isolated were then further purified by TLC and preparative HPLC in which a fraction with Rf 0.73 and RT 10.3 was obtained. Cucurbitacin E with molecular weight of 557 from the fraction was finally identified by subsequent structural analysis of LC-MS/MS. The production of cucurbitacin E peaked with 224.7 mg/kg at 4 days of germination at $20^{\circ}C$ with the water supply at ntervals of 48 hrs in the darkness, while that of cucurbitacin E reached 146.7 mg/kg in the brightness. In vitro-cell based assays demonstrated that the isolated and purified cucurbitacin E inhibited proliferation of A549 lung cancer cells and suppressed expression of the IL-$1{\beta}$- or PMA-induced cyclooxygenase-2, an inflammatory protein in A549 cells, suggesting its anti-proliferative and anti-inflammatory activities.

Studies on Genetic Toxicity of Epoxidized Soy Bean Oil (에폭시화 대두유의 유전독성 연구)

  • 한의식;정해관;김종원;박미선;엄미옥;강혁준;민수진;오혜영
    • Journal of Food Hygiene and Safety
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    • v.16 no.2
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    • pp.145-151
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    • 2001
  • EpoxidiBed soy bean oil (ESBO) is a plasticizer of PVC which is being widely used as a gaskets for the lid of glass jars including baby food. Using reverse mutation assay, chromosome aberration test and micronucleus test, ESBO were evaluated the mutagenicity. In the reverse mutation test, ESBO did not induced mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA102 with and without metabolic activation. In the chromosome aberration test using CHL cells, the results showed no increased structural and numerical aberrations in the concentration of sample producing cytotoxicity with and without metabolic activation. The in vivo induction of micronuclei was measured in polychromatic erythrocytes of bone marrow of young (3weeks old) and adult (6 weeks old) ddY mice of both sex. At 24 hours after treatment with ESBO 20, 10, 5, 2.5 g/B.W. kg/corn oil 10 ml by oral route animals were sacrificed and bone marrow cells were prepared for smear slides. The results showed no increased micronucleated polychromatic erythrocytes regardless of sex and age. It was concluded that water soluble ESBO did not show certain genotoxicity within our studies conducted.

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Effects of Loquat (Eriobotrya japonica Lindl.) Ethanol Extracts of Different Aerial Parts on Antioxidant Activity and Antiproliferation of Human Cancer Cells (비파 부위별 에탄올 추출물의 항산화 활성 및 암세포 증식 억제효과)

  • Lee, Hwan;Kim, Yeon-Kyoung;Lee, Hyun-Joo;Lee, Jae-Joon
    • The Korean Journal of Community Living Science
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    • v.27 no.2
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    • pp.211-220
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    • 2016
  • The current study was carried out to determine the effects of the seed, flesh (seedless fruit), and leaf of loquat (Eriobotrya japonica Lindle.) on antioxidative activity and anti-proliferation in human cancer cells. Total polyphenol contents of loquat seed, flesh, and leaf ethanol extracts were found to be 17.77, 32.32, and 28.08 mg/g, respectively. Also, total flavonoid contents of loquat seed, flesh, and leaf ethanol extracts were found to be 18.77, 28.73, and 21.35 mg/g, respectively. The $IC_{50}$ values of DPPH hydroxyl scavenging of loquat seed, flesh, and leaf ethanol extracts were 0.049, 0.063, and 0.042 mg/mL, respectively. Antioxidative indexes of loquat leaf and seed ethanol extracts was highly and it was similar to the BHA and BHT. The antioxidative activities in loquat seed and leaf ethanol extracts were higher in loquat flesh. The antiproliferation effect of loquat seed and leaf ethanol extracts on liver cancer cell line (H460), stomach cancer cell line (AGS) and lung cancer cell line (A549) showed higher values compared with the flesh ethanol extracts. These results indicate that loquat ethanol extracts may play a positive role in antioxidative properties and cancer prevention.

Attenuation of airway hyperreactivity and inflammation by Cheongsangbiyeum administration in a mouse model of asthma (마우스 천식모델에서 청상비음(淸上秘飮)의 기도 과민반응 및 염증의 억제 효과)

  • Kim, San;Sung, Byung-Gon;Lee, Sung-Jin;Lim, Kyu-Sang
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.19 no.2
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    • pp.1-18
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    • 2006
  • Objective : Although management of asthma has become increasingly effective, its cure remains elusive, necessitating a new modality to prevent or eliminate causes triggering clinical progress. Based in the clinical experiences, a novel decoration Cheongsangbiyeum (CSB), has been developed to treat asthma, which consists of Polyporus, Semen Myristicae, Pericarpium citri Reticulatae, Rhizoma Cimicifugae, Cortex Albizziae, Fructus Rubi, Rhizoma Zedoariae, and Rhizoma Rhei. In the current study, its anti-asthmatic efficacy was evaluated using a mouse model of asthma. Methods : Experimental allergic asthma was induced by repeated intraperitioneal sensitization and intranasal challenge of ovalbumin (OVA). Water extract of CSB (1 mg/mouse/day) was administrated orally whereas control mice on given with identical volume of phosphate-buffered saline (PBS) for 5 days during the course of antigen challenge. When airway hyperreactivity(AHR) measured by ${\bata}-methacoline-induced$ airflow obstruction was compared, AHR of CSB-treated mice was significantly lower than those of control mice, indicating that CM extract can attenuate an asthmatic symptom. Airway recruitment of leukocytes and eosinophils was also markedly reduced by CSB treatment suggesting that oral treatment of CSB can alleviate the airway inflammation. For a better understanding of possible mechanisms underlying anti-asthmatic effet of CSB, cytokine (IL-4, IL-5, IL-13 and $IFN{\gamma}$ levels in bronchoalveola lavage fluid (BALF) and lung tissues were determined. Results : The results showed that cytokine levels were significantly lowered by CSB treatment. Additionally, number of draining lymph node cells was significantly lower than those of control mice. These data indicate that CSB suppress in vivo allergen-specific response. However, notably, levels of type 2 cytokines such as IL-5 and IL-13 were more profoundly influenced. Moreover, in vitro OVA-specific proliferative response and type 2 cytokine (IL-4, IL-5 and IL-13) production lymph node cells was markedly decreased in CSB-treated mice, whereas their $IFN{\gamma}$ production was not significantly altered Thrse data clearly showed a preferential inhibition of type 2 T cell (Th2) response by CSB treatment. This finding was also supported by serum antibody data showing that levels of OVA-specific type 2 antibodies, IgE and IgG1, in CSB-treated mice were significantly lower than in control mice, while type 1 antibody, IgG2a level m rather higher than controls, although the difference was in significant. Conclusions : In conclusion, oral administration of CSB attenuates asthmatic manifestations including AHR ad airway recruitment of eosinophils in a mouse model which possibly results from selective inhibition of Th2 cell response to allergen. Our data suggest a potential clinical application of CSB for control of allergic asthma.

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Inhibition Effect of Cell Proliferation and Apoptosis by Inonotus obliquus in Human Glioblastoma U-87 MG Cells (차가버섯 추출물에 의한 신경교모세포종 U-87 MG 세포의 증식 억제 효과)

  • Shin, Jung-A;Park, Joo Hyun;Kim, Sun Hee;Song, Kwan Yong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.7
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    • pp.1022-1028
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    • 2013
  • Chaga mushroom (Inonotus obliquus) was considered a functional food with an anti-cancer effect in colon, gastric, and lung cancer. Therefore, this study was conducted in order to elucidate the effect of chaga mushroom extract in brain cancer. Glioblastoma U-87 MG cells were used in investigation of cell survivability, apoptosis, and cell cycle arrest analysis. Treatment with various concentrations of chaga mushroom extract resulted in inhibition of cell proliferation and cell cycle arrest. Although caspase-3 expression was increased over $100{\mu}g/mL$ of chaga mushroom extract treatment, apoptosis factors with Bcl-2, Bax and p53 did not change. In analysis of cell cycle regulatory factors, expression of cyclin D1 and CDK2 decreased in a dose-dependent manner. We have demonstrated the anti-cancer effect of chaga mushroom extract in glioblastoma, which may be mediated by activation of the caspase pathway and induction of cell cycle arrest.