• Title/Summary/Keyword: Lung cells

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Identification of Selective STAT1 Inhibitors by Computational Approach

  • Veena Jaganivasan;Dona Samuel Karen;Bavya Chandrasekhar
    • Journal of Integrative Natural Science
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    • v.16 no.3
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    • pp.81-95
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    • 2023
  • Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual - Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.

Histopathological evaluation of the lungs in experimental autoimmune encephalomyelitis

  • Sungmoo Hong;Jeongtae Kim;Kyungsook Jung;Meejung Ahn;Changjong Moon;Yoshihiro Nomura;Hiroshi Matsuda;Akane Tanaka;Hyohoon Jeong;Taekyun Shin
    • Journal of Veterinary Science
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    • v.25 no.3
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    • pp.35.1-35.13
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    • 2024
  • Importance: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by inflammation within the central nervous system. However, inflammation in non-neuronal tissues, including the lungs, has not been fully evaluated. Objective: This study evaluated the inflammatory response in lungs of EAE mice by immunohistochemistry and histochemistry. Methods: Eight adult C57BL/6 mice were injected with myelin oligodendrocyte glycoprotein35-55 to induce the EAE. Lungs and spinal cords were sampled from the experimental mice at the time of sacrifice and used for the western blotting, histochemistry, and immunohistochemistry. Results: Histopathological examination revealed inflammatory lesions in the lungs of EAE mice, characterized by infiltration of myeloperoxidase (MPO)- and galectin-3-positive cells, as determined by immunohistochemistry. Increased numbers of collagen fibers in the lungs of EAE mice were confirmed by histopathological analysis. Western blotting revealed significantly elevated level of osteopontin (OPN), cluster of differentiation 44 (CD44), MPO and galectin-3 in the lungs of EAE mice compared with normal controls (p < 0.05). Immunohistochemical analysis revealed both OPN and CD44 in ionized calcium-binding adapter molecule 1-positive macrophages within the lungs of EAE mice. Conclusions and Relevance: Taken together, these findings suggest that the increased OPN level in lungs of EAE mice led to inflammation; concurrent increases in proinflammatory factors (OPN and galectin-3) caused pulmonary impairment.

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.

In Vitro Genotoxicity Test of m-Phenylenediamine Using the Chromosomal Aberration Assay in Cultured Mammalian Cells

  • Soo-jin Yoo;Yong-hyun Chung;Yong-taek Kwon;Jin-kwon Kim;Yeon-su Baek;Su-ho Lee;Myeong-ju Shin;Jung-hun Lee;Ji-yoen Woo;Dong-hyun Kim
    • International journal of advanced smart convergence
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    • v.13 no.4
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    • pp.543-549
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    • 2024
  • On February 21, 2023, the Ministry of Food and Drug Safety in Korea designated five hair dye ingredients, including m-phenylenediamine, as prohibited substances in cosmetics due to potential genotoxicity, which may cause genetic damage or mutations in humans. Based on the revised regulations, products containing these ingredients have been banned from manufacture and import as of August 22, 2023. However, products manufactured or imported before this date may still be sold until August 21, 2025. Therefore, m-phenylenediamine, which has already been verified to exhibit genotoxicity, was selected as the test substance for this study. The chromosomal aberration test was conducted in compliance with OECD TG 473. Mammalian cell lines, specifically the Chinese Hamster Lung (CHL/IU) cell line, were used. The test examined the chromosomal aberration-inducing potential of the test substance with and without metabolic activation. Genotoxicity assessment is not conducted based on a single test; instead, it requires a 3-battery approach, comprising from three different tests. Preliminary studies have shown a positive response in the reverse mutation assay for m-phenylenediamine. This study adds the chromosomal aberration test to compare the results, supporting the validity of a 3-battery approach and suggesting the ethical viability of cell-based toxicity testing to assess chemical hazards.

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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