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Suppression of Monosodium Urate-induced NLRP3 Inflammasome Activation by Garlic-derived Sulfur-containing Phytochemicals is Associated with Blocking ROS Generation in RAW 264.7 Macrophages (RAW 264.7 대식세포에서 마늘 유래 황 함유 화합물에 의한 요산 유도 inflammasome 활성화의 억제는 ROS 생성 차단과 연관성이 있음)

  • Min Yeong Kim;Yung Hyun Choi
    • Journal of Life Science
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    • v.33 no.4
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    • pp.349-356
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    • 2023
  • Gout, a chronic inflammatory arthritic disease, is characterized by hyperuricemia. Gout can be induced by an inflammatory response to monosodium urate (MSU) crystals mediated by pro-inflammatory cytokine release following activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Many sulfur-containing phytochemical compounds in garlic (Allium sativum L.) are considered active ingredients because of their potential pharmacological benefits for various diseases, but their efficacy in NLRP3 inflammasome activation-mediated gout has not been demonstrated. In this study, we investigated whether diallyl disulfide (DADS) and diallyl trisulfide (DATS), representative garlic-derived sulfur compounds, have an inhibitory effect on MSU-induced NLRP3 inflammasome activation. Our results showed that under non-cytotoxic conditions, DADS and DATS significantly blocked nitric oxide production and interleukin (IL)-1β release in response to MSU in lipopolysaccharide (LPS)-primed RAW 264.7 macrophages. DADS and DATS also attenuated enhanced expression of NLRP3 and its adapter protein, apoptosis-associated speck-like protein, which was associated with downregulation of and caspase-1 p20 and IL-1β expression, suggesting that MSU-induced LRP3 inflammasome activation was counteracted by DADS and DATS. Furthermore, DADS and DATS blocked oxidative stress, an upstream event for NLRP3 inflammasome activation, as evidenced by the fact that they scavenged reactive oxygen species (ROS) production. Taken together, our findings demonstrate that DADS and DATS suppressed NLRP3 inflammasome activation by inhibiting the ROS/NLRP3 pathway and that they have potential as treatments for NLRP3-dependent gouty arthritis.

Indigo Naturalis in Inflammatory Bowel Disease: mechanisms of action and insights from clinical trials

  • Hyeonjin Kim;Soohyun Jeong;Sung Wook Kim;Hyung-Jin Kim;Dae Yong Kim;Tae Han Yook;Gabsik Yang
    • Journal of Pharmacopuncture
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    • v.27 no.2
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    • pp.59-69
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    • 2024
  • This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1β) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-β) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

Cigarette Smoke Extract-Treated Mouse Airway Epithelial Cells-Derived Exosomal LncRNA MEG3 Promotes M1 Macrophage Polarization and Pyroptosis in Chronic Obstructive Pulmonary Disease by Upregulating TREM-1 via m6A Methylation

  • Lijing Wang;Qiao Yu;Jian Xiao;Qiong Chen;Min Fang;Hongjun Zhao
    • IMMUNE NETWORK
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    • v.24 no.2
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    • pp.3.1-3.23
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    • 2024
  • Cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs)-derived exosomes accelerate the progression of chronic obstructive pulmonary disease (COPD) by upregulating triggering receptor expressed on myeloid cells 1 (TREM-1); however, the specific mechanism remains unclear. We aimed to explore the potential mechanisms of CSE-treated MAECs-derived exosomes on M1 macrophage polarization and pyroptosis in COPD. In vitro, exosomes were extracted from CSE-treated MAECs, followed by co-culture with macrophages. In vivo, mice exposed to cigarette smoke (CS) to induce COPD, followed by injection or/and intranasal instillation with oe-TREM-1 lentivirus. Lung function and pathological changes were evaluated. CD68+ cell number and the levels of iNOS, TNF-α, IL-1β (M1 macrophage marker), and pyroptosis-related proteins (NOD-like receptor family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain, caspase-1, cleaved-caspase-1, gasdermin D [GSDMD], and GSDMD-N) were examined. The expression of maternally expressed gene 3 (MEG3), spleen focus forming virus proviral integration oncogene (SPI1), methyltransferase 3 (METTL3), and TREM-1 was detected and the binding relationships among them were verified. MEG3 increased N6-methyladenosine methylation of TREM-1 by recruiting SPI1 to activate METTL3. Overexpression of TREM-1 or METTL3 negated the alleviative effects of MEG3 inhibition on M1 polarization and pyroptosis. In mice exposed to CS, EXO-CSE further aggravated lung injury, M1 polarization, and pyroptosis, which were reversed by MEG3 inhibition. TREM-1 overexpression negated the palliative effects of MEG3 inhibition on COPD mouse lung injury. Collectively, CSE-treated MAECs-derived exosomal long non-coding RNA MEG3 may expedite M1 macrophage polarization and pyroptosis in COPD via the SPI1/METTL3/TREM-1 axis.

Future Development of Genetics and the Broiler (BROILER 육종기술의 전망)

  • 오봉국
    • Korean Journal of Poultry Science
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    • v.8 no.1
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    • pp.1-5
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    • 1981
  • In trying to predict the effect of genetics on the broiler in the year 2000, this is a relatively short period of time as far as broiler genetics in concerned. Modern broiler genetics started around 1945 and tremendous gains when made in past 35 years. Futher improvements on broiler will depend on the evolution and revolution: 1. Evolution: (1) Growth rate has been made 4-5% per year. (2) Feed conversion has improved approximately 1% per year. (3) Abdominal fat is becoming a major complaint in broiler. (4) Because of the changing life-style, broiler meat sales in the future will be more and more in cut-up form. (5) Breeding for stress resistance and selection for docile temperament can be important in order to funker improve fled efficiency. (6) In female parent stock, reproduction characteristics are in many can negatively correlated with the desired broiler traits. (7) Egg production and hatchability in moot commercial parent nod m at a fairly high level. (8) In male parent stock, the heavier and mon super-meat-type male lines are desired to Product better broilers. 2. Revolution: Trying to forecast revolutionary change in broiler genetics is highly speculative, as sudden change are aften unpredictable. (1) Species hybridization, such as a turkey-chicken cross (2) Biochemical tools, such as blood typing. (3) Mutation breeding by radiation or chemical mutagentia. (4) Broiler breeding would be to change the phenotypic appearance by single gene, such as naked, wingless. (5) Changes in production techniques. such as growing in cage or growing in filtered air positive pressure houses.

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A study on the Types of Utilization and Administration of Common Forests in Korea (마을공동소유림(共同所有林)의 이용(利用) 및 관리실태(管理實態) 조사연구(調査硏究))

  • Lee, Mahn Woo
    • Journal of Korean Society of Forest Science
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    • v.61 no.1
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    • pp.60-68
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    • 1983
  • Ever since the day of pre-modernized society where the farming skill had been in the stagnant condition, the common farmwoodlands have been utilized in common (collectivelly) by villagers in order to harvest farmwoodlands and fuelwoods. Later, during the process of modernization, most of the common farmwoodlands were transferred into national or public forests by the administrative enforcement, but there were still various types of village (common) forests such as the common forests owned by joint owners, village block associations, village forest productive societies, Village Forestry Association(V.F.A.), and the national or public forests leased to V.F.A. As Village Forestry Association is organized with a few villages, each of common forests ow nod to the villages is obliged to be diversely controlled by other managers than the chief of V.F.A. Therefore, it is to be desired that the control of common forests should be under Gun Forestry Association Union. While the rate of the use of common forests for fuelwoods and cemetery has been considerably high, villagers wish to promote the timber forest establishment through the collective management by their improved farming skills and economical situations. In these present circumstances the village forest productive societies should be guided to work in closer cooperation with Gun Forestry Association Union. Since the management of common forests is still extensive, it still remains in the semi-management condition under which we can not find any management plan or measure to control forest damage. Especially the small area common forests should have appropriate size for the joint management. This will promote the forest productivity through the lease for reforestation of disposable national forests or public county forests and the contracts for profit sharing. Today owing to increasing forest value, frequent dispute has occurred on the common right telated to the village forests and rationalization of forest management has been disregarded. If a necessary measure were taken to control the dispute such as transferring the registeration right of ownership to the village forest productive society, the confidence of local inhabitants can be regained and the productivity of forests can be naturally increased.

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육계사료에 CLA와 다른 유지의 첨가.급여가 생산능력에 미치는 영향비교

  • 류명선;김은성;김상호;최형송;정문웅;류경선
    • Proceedings of the Korea Society of Poultry Science Conference
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    • 2001.11a
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    • pp.89-91
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    • 2001
  • Two experiments were conducted to compare the dietary supplemental influence of conjugated linoleic acid(CLA), soybean oil(SBO) and commercial tallow(U) on performance and physiological related factor of broiler chicks. Diets contained CP 21.5, 19% and ME 3,100, 3,100kcal/kg for starting and finishing period. Each three levels(1.0, 2.0, 3.0%) of CLA, SBO, CT were supplemented to basal diets. Five hundred forty and three hundred sixty chicks were applied to 3${\times}$3, 2${\times}$3 factorial design with four replicates in Expt 1 and 2. Weight gain, food intake and feed conversion were weekly examined. Blood cholesterol, ND antibody titer, blood components and were measured at the end of experiment. Metabolizable energy(ME) were measured through the metabolic feeding trial in each oil. ME was 8,542, 9,179, 8,133 kcal/kg in CLA, SBO and CT, respectively. In Expt 1, weight gain of chicks fed 1% dietary oil was significantly lower than other treatments(P<0.05). Feed conversion was significantly improved in SBO supplemental groups of all treatments(P<0.05). In Expt 2, CLA supplements increased weight gain significantly for finishing period(P<0.05) compared to that of other treatments. Feed conversion of chicks fed 2% dietary oil was significantly improved relative that of 3%(P<0.05). HDL of 3% dietary supplemental oil treatments was significantly higher for finishing and starting period in Expt 1 and 2, respectively than other treatments(P<0.05). There were no significantly different M Antibody titer in Expt 1, but showed significance between dietary supplemental oil in Expt 2(P<0.05). CLA content of breast meat was 12.23, 18.74, 25.67 mg/g in 1, 2, and 3% CLA treatments and significantly different between them(P<0.05). As the results of these experiments, feeding CLA tended to improve the weight gain compared In that of other dietary oil, but was not increase the ND antibody titer of broiler chciks. CLA content of breast meat also showed the significance at different level of dietary supplement.

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Flavonoid Biosynthesis: Biochemistry and Metabolic Engineering (Flavonoid 생합성:생화학과 대사공학적 응용)

  • Park, Jong-Sug;Kim, Jong-Bum;Kim, Kyung-Hwan;Ha, Sun-Hwa;Han, Bum-Soo;Kim, Yong-Hwan
    • Journal of Plant Biotechnology
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    • v.29 no.4
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    • pp.265-275
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    • 2002
  • Flavonoid biosynthesis is one of the most extensively studied areas in the secondary metabolism. Due to the study of flavonoid metabolism in diverse plant system, the pathways become the best characterized secondary metabolites and can be excellent targets for metabolic engineering. These flavonoid-derived secondary metabolites have been considerably divergent functional roles: floral pigment, anticancer, antiviral, antitoxin, and hepatoprotective. Three species have been significant for elucidating the flavonoid metabolism and isolating the genes controlling the flavonoid genes: maize (Zea mays), snapdragon (Antirrhinum majus) and petunia (Prtunia hybrida). Recently, many genes involved in biosynthesis of flavonoid have been isolated and characterized using mutation and recombinant DNA technologies including transposon tagging and T-DNA tagging which are novel approaches for the discovery of uncharacterized genes. Metabolic engineering of flavonoid biosynthesis was approached by sense or antisense manipulation of the genes related with flavonoid pathway, or by modified expression of regulatory genes. So, the use of a variety of experimental tools and metabolic engineering facilitated the characterization of the flavonoid metabolism. Here we review recent progresses in flavonoid metabolism: confirmation of genes, metabolic engineering, and applications in the industrial use.

Surface maker and gene expression of human adipose stromal cells growing under human serum. (인체혈청 하에서 배양한 인체지방기질줄기세포의 표면항원 및 유전자 발현)

  • Jun, Eun-Sook;Cho, Hyun-Hwa;Joo, Hye-Joon;Kim, Hoe-Kyu;Bae, Yong-Chan;Jung, Jin-Sup
    • Journal of Life Science
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    • v.17 no.5 s.85
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    • pp.678-686
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    • 2007
  • Human mesenchymal stem cells(hMSC), that have been reported to be present in bone marrow, adipose tissues, dermis, muscles and peripheral blood, have the potential to differentiate along different lineages including those forming bone, cartilage, fat, muscle and neuron. Therefore, hMSC are attractive candidates for cell and gene therapy. The optimal conditions for hMSC expansion require medium supplemented with fetal bovine serum(FBS). Some forms of cell therapy will involve multiple doses, raising a concern over immunological reactions caused by medium-derived FBS proteins. Previously, we have shown that hADSC can be cultured in human serum(HS) during their isolation and expansion, and that they maintain their proliferative capacity and ability for multilineage differentiation and promote engraftment of peripheral blood-derived CD34 cells mobilized from bone marrow in NOD/SCID mice. In this study we determined whether hADSC grown in HS maintain surface markers expression similar with cells grown in FBS during culture expansion and compared gene expression profile by Affymetrix microarray. Flow cytometry analysis showed that HLA-DR, CD117, CD29 and CD44 expression in HS-cultured hADSC during culture expansion were similar with that in FBS-cultured cells. However, the gene expression profile in HS-cultured hADSC was significantly different from that in FBS-cultured cells. Therefore, these data indicated that HS-cultured hADSC should be used in vivo animal study of hADSC transplantation for direct extrapolation of preclinical data into clinical application.