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Resolvin D5, a Lipid Mediator, Inhibits Production of Interleukin-6 and CCL5 Via the ERK-NF-κB Signaling Pathway in Lipopolysaccharide-Stimulated THP-1 Cells

  • Chun, Hyun-Woo;Lee, Jintak;Pham, Thu-Huyen;Lee, Jiyon;Yoon, Jae-Hwan;Lee, Jin;Oh, Deok-Kun;Oh, Jaewook;Yoon, Do-Young
    • Journal of Microbiology and Biotechnology
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    • v.30 no.1
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    • pp.85-92
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    • 2020
  • One of the omega-3 essential fatty acids, docosahexaenoic acid (DHA), is a significant constituent of the cell membrane and the precursor of several potent lipid mediators. These mediators are considered to be important in preventing or treating several diseases. Resolvin D5, an oxidized lipid mediator derived from DHA, has been known to exert anti-inflammatory effects. However, the detailed mechanism underlying these effects has not yet been elucidated in human monocytic THP-1 cells. In the present study, we investigated the effects of resolvin D5 on inflammation-related signaling pathways, including the extracellular signal-regulated kinase (ERK)-nuclear factor (NF)-κB signaling pathway. Resolvin D5 downregulated the production of interleukin (IL)-6 and chemokine (C-C motif) ligand 5 (CCL5). Additionally, these inhibitory effects were found to be modulated by mitogen-activated protein kinase (MAPK) and NF-κB in lipopolysaccharide (LPS)-treated THP-1 cells. Resolvin D5 inhibited the LPS-stimulated phosphorylation of ERK and translocation of p65 and p50 into the nucleus, resulting in the inhibition of IL-6 and CCL5 production. These results revealed that resolvin D5 exerts anti-inflammatory effects in LPS-treated THP-1 cells by regulating the phosphorylation of ERK and nuclear translocation of NF-κB.

Cholera Toxin B Subunit-Porphyromonas gingivalis Fimbrial Antigen Fusion Protein Production in Transgenic Potato

  • Lee, Jin-Yong;Kim, Mi-Young;Jeong, Dong-Keun;Yang, Moon-Sik;Kim, Tae-Geum
    • Journal of Plant Biotechnology
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    • v.36 no.3
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    • pp.268-274
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    • 2009
  • Porphyromonas gingivalis, the gram-negative anaerobic oral bacterium, initiates periodontal disease by binding to saliva-coated oral surface. The cholera toxin B subunit (CTB) genetically linked to FimA1 (1-200 aa) or FimA2 (201-337 aa) of the P. gingivalis fimbrial antigen were introduced into Solanum tuberosum cells by Agrobacterium tumefaciens-mediated transformation method. The integration of CTB-FimA1 or CTB-FimA2 fusion genes were confirmed in the chromosome of transformed leaves by genomic DNA PCR amplification method. Synthesis and assembly of the CTB-FimA fusion proteins into oligomeric structures with pentamer size was detected in transformed tuber extracts by immunoblot analysis. The binding activities of CTB-FimA fusion proteins to intestinal epithelial cell membrane receptors were confirmed by GM1-ganglioside enzyme-linked immunosorbent assay (GM1-ELISA). The ELISA showed that the expression levels of the CTB-FimA1 or CTB-FimA2 fusion proteins were 0.0019, 0.002% of the total soluble protein in transgenic tuber tissues, respectively The synthesis of CTB-FimA monomers and their assembly into biologically active oligomers in transformed potato tuber tissues demonstrates the feasibility of using edible plants for the production of enterocyte targeted fimbrial antigens that could elicit mucosal immune responses.

Chikungunya Virus nsP2 Impairs MDA5/RIG-I-Mediated Induction of NF-κB Promoter Activation: A Potential Target for Virus-Specific Therapeutics

  • Bae, Sojung;Lee, Jeong Yoon;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
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    • v.30 no.12
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    • pp.1801-1809
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    • 2020
  • Chikungunya virus (CHIKV) was first identified in 1952 as a causative agent of outbreaks. CHIKV is transmitted by two mosquito species, Aedes aegypti and A. albopictus. Symptoms after CHIKV infection in human are typically fever and joint pain, but can also include headache, muscle pain, joint swelling, polyarthralgia, and rash. CHIKV is an enveloped single-stranded, positive-sense RNA virus with a diameter of approximately 70 nm. The pathogenesis of CHIKV infection and the mechanism by which the virus evades the innate immune system remain poorly understood. Moreover, little is known about the roles of CHIKV-encoded genes in the viral evasion of host immune responses, especially type I interferon (IFN) responses. Therefore, in the present study, we screened CHIKV-encoded genes for their regulatory effect on the activation of nuclear factor kappa B (NF-κB), a critical transcription factor for the optimal activation of IFN-β. Among others, non-structural protein 2 (nsP2) strongly inhibited melanoma differentiation-associated protein 5 (MDA5)-mediated induction of the NF-κB pathway in a dose-dependent manner. Elucidation of the detailed mechanisms of nsP2-mediated inhibition of the MDA5/RIG-I signaling pathway is anticipated to contribute to the development of virus-specific therapeutics against CHIKV infection.

Reserpine treatment activates AMP activated protein kinase (AMPK)

  • Park, Rackhyun;Lee, Kang Il;Kim, Hyunju;Jang, Minsu;Ha, Thi Kim Quy;Oh, Won Keun;Park, Junsoo
    • Natural Product Sciences
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    • v.23 no.3
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    • pp.157-161
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    • 2017
  • Reserpine is a well-known medicine for the treatment of hypertension, however the role of reserpine in cell signaling is not fully understood. Here, we report that reserpine treatment induces the phosphorylation of AMP activated protein kinase (AMPK) at threonine 172 (T172) in PC12 cells. Phosphorylation of AMPK T172 is regulated by upstream signaling molecules, and the increase of phospho-T172 indicates that AMPK is activated. When we examined the FOXO3a dependent transcription by using the FHRE-Luc reporter assay, reserpine treatment repressed the FHRE-Luc reporter activity in a dose dependent manner. Finally, we showed that reserpine treatment induced the phosphorylation of AMPK as well as cell death in MCF-7 cells. These results suggest that AMPK is a potential cellular target of reserpine.

Increasing Sulforaphane Formation in Broccoli Sprouts by Radish Sprouts Additions

  • Gi-Chang Kim;Mi Jang;Hab-Hwa Beak;In-Guk Hwang;Hae-Ju Kang;Byung-Soon Hwang;Ji-Young Kim;Chan-Mi Park
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2020.12a
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    • pp.78-78
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    • 2020
  • Cruciferous plants such as broccoli and radish contain glucosinolate, which is a bioactive precursor that is most often used in Korean foods and is unique as a food ingredient. In addition, it contains various other phytochemicals and is promising as a health-oriented food material. In particular, Sulforaphane is a hydrolyzate of the glucosinolate, which has a more beneficial effect on the human body. Glucosinolate may be hydrolyzed by enzymes called myrosinase, which is voluntarily possessed by cruciferous plants. However, the ESP(Epithiospecifier protein) in broccoli sprouts could acts competitively with myrosinase, and convert to the less bioactive sulforaphane nitrile form. Therefore, we improved the yielding of sulforaphane in broccoli sprouts with a new method. We induce inactivation of the ESP protein by heat treatment. At this time, a myrosinase was introduced from the radish sprout because myrosinase in broccoli sprouts is also denatured by heat treatment. According to the results, we have confirmed by GC / MS that formation of sulforaphane increases more than 7 fold using set heating and mixing conditions.

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Peptide Analysis and the Bioactivity of Whey Protein Hydrolysates from Cheese Whey with Several Enzymes

  • Jeewanthi, Renda Kankanamge Chaturika;Kim, Myeong Hee;Lee, Na-Kyoung;Yoon, Yoh Chang;Paik, Hyun-Dong
    • Food Science of Animal Resources
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    • v.37 no.1
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    • pp.62-70
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    • 2017
  • The aim of this study was identifying a suitable food grade enzymes to hydrolyze whey protein concentrates (WPCs), to give the highest bioactivity. WPCs from ultrafiltration retentate were adjusted to 35% protein (WPC-35) and hydrolyzed by enzymes, alcalase, ${\alpha}-chymotrypsin$, pepsin, protease M, protease S, and trypsin at different hydrolysis times (0, 0.5, 1, 2, 3, 4, and 5 h). These 36 types of hydrolysates were analyzed for their prominent peptides ${\beta}-lactoglobulin$ (${\beta}-Lg$) and ${\alpha}-lactalbumin$ (${\alpha}-La$), to identify the proteolytic activity of each enzyme. Protease S showed the highest proteolytic activity and angiotensin converting enzyme inhibitory activity of IC50, 0.099 mg/mL (91.55%) while trypsin showed the weakest effect. Antihypertensive and antioxidative peptides associated with ${\beta}-Lg$ hydrolysates were identified in WPC-35 hydrolysates (WPH-35) that hydrolyzed by the enzymes, trypsin and protease S. WPH-35 treated with protease S in 0.5 h, responded positively to usage as a bioactive component in different applications of pharmaceutical or related industries.

Changes in protein content and bioactive activity in Phellinus linteus HN00K9 cultured on oat (목질진흙버섯HN00K9 배양 귀리의 단백질함량 및 생물활성 변화)

  • Ja-Yoon Kim;Hee-Wan Kang
    • Journal of Mushroom
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    • v.22 no.3
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    • pp.102-106
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    • 2024
  • This study aimed to analyze crude protein, amino acid and bioactive changes in Phellinus linteus HN00K9 cultured oat. The crude protein content of P. linteus cultured oat (PCO) was 12.9%, which was higher than that of uncultured oats (UCO) as control at 11.26%. The total free amino acid contents of PCO and UCO were 11,4 mg/100 g and 9,686.205 mg/100 g, respectively. Glutamic acid accounted for 21% of the total amino acids of PCO, and the histidine content was increased by more than 51% in PCO compared to UCO. The total polyphenol content of PCO was 275 mg GAE/g, which was more than twice that of UCO (135 mg). The DPPH radical scavenging activity was 15.5% in PCO, which was more than five times that of UCO (3.5%). The β-glucan content of PCO was 12.5 g/100 g, which was more than five times that of UCO (3.2 g/100 g). Therefore, it is believed that PCO can be utilized as a material for various functional foods.

Citrus Fruits and their Bioactive Ingredients: Leading Four Horsemen from Front

  • Farooqi, Ammad Ahmad;Wang, Zhiqiang;Hasnain, Sidra;Attar, Rukset;Aslam, Ayesha;Mansoor, Qaisar;Ismail, Muhammad
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2575-2580
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    • 2015
  • Cancer is a multifaceted and genomically complex disease and rapidly accumulating high impact research is deepening our understanding related to the mechanisms underlying cancer development, progression and resistance to therapeutics. Increasingly it is being realized that genetic/epigenetic mutations, inactivation of tumor suppressor genes, overexpression of oncogenes, deregulation of intracellular signaling cascades and loss of apoptosis are some of the extensively studied aspects. Confluence of information suggested that rapidly developing resistance to therapeutics is adding another layer of complexity and overwhelmingly increasing preclinical studies are identifying different natural agents with efficacy and minimal off-target effects. We partition this multi-component review into citrus fruits and their bioactive ingredients mediating rebalancing of pro- and anti-apoptotic proteins to induce apoptosis in resistant cancer cells. We also discuss how oncogenic protein networks are targeted in cancer cells and how these findings may be verified in preclinical studies.

Anti-inflammatory Activity of Sambucus Plant Bioactive Compounds against TNF-α and TRAIL as Solution to Overcome Inflammation Associated Diseases: The Insight from Bioinformatics Study

  • Putra, Wira Eka;Salma, Wa Ode;Rifa'i, Muhaimin
    • Natural Product Sciences
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    • v.25 no.3
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    • pp.215-221
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    • 2019
  • Inflammation is the crucial biological process of immune system which acts as body's defense and protective response against the injuries or infection. However, the systemic inflammation devotes the adverse effects such as multiple inflammation associated diseases. One of the best ways to treat this entity is by blocking the tumor necrosis factor alpha ($TNF-{\alpha}$) and TNF-related apoptosis-inducing ligand (TRAIL) to avoid the proinflammation cytokines production. Thus, this study aims to evaluate the potency of Sambucus bioactive compounds as anti-inflammation through in silico approach. In order to assess that, molecular docking was performed to evaluate the interaction properties between the $TNF-{\alpha}$ or TRAIL with the ligands. The 2D structure of ligands were retrieved online via PubChem and the 3D protein modeling was done by using SWISS Model. The prediction results of the study showed that caffeic acid (-6.4 kcal/mol) and homovanillic acid (-6.6 kcal/mol) have the greatest binding affinity against the $TNF-{\alpha}$ and TRAIL respectively. This evidence suggests that caffeic acid and homovanillic acid may potent as anti-inflammatory agent against the inflammation associated diseases. Finally, this study needs further examination and evaluation to validate the potency of Sambucus bioactive compounds.

Potential Prebiotic Properties of Whey Protein and Glycomacropeptide in Gut Microbiome

  • Bryna Rackerby;Hoang Ngoc M. Le;Avery Haymowicz;David C. Dallas;Si Hong Park
    • Food Science of Animal Resources
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    • v.44 no.2
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    • pp.299-308
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    • 2024
  • Proteins in whey have prebiotic and antimicrobial properties. Whey protein comprises numerous bioactive proteins and peptides, including glycomacropeptide (GMP), a hydrophilic casein peptide that separates with the whey fraction during cheese making. GMP has traditionally been used as a protein source for individuals with phenylketonuria and also has prebiotic (supporting the growth of Bifidobacterium and lactic acid bacteria) and antimicrobial activities. GMP supplementation may help positively modulate the gut microbiome, help treat dysbiosis-related gastrointestinal disorders and improve overall health in consumers.