• Title/Summary/Keyword: resistance inhibition

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Isolation of Garlic Resistant Lactic Acid Bacteria for Feed Additives (사료용 생균제 개발을 위한 마늘 내성 유산균의 분리)

  • Kim, Yu-Jin;Jang, Seo-Jung;Park, Jung-Min;Kim, Chang-Uk;Park, Young-Seo
    • Food Engineering Progress
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    • v.13 no.4
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    • pp.352-359
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    • 2009
  • Lactic acid bacteria was isolated for the production of probiotic animal feed supplemented with garlic and its antimicrobial properties were investigated. A total of 112 strains of lactic acid bacteria which grew on the medium containing garlic extract were isolated from kimchi, jeotgal, and jangachi. Among them 14 strains were tested for acidand bile salt-resistance as well as antimicrobial activities against animal pathogenic bacteria such as Salmonella choleraesuis, Escherichia coli, Staphylococcus aureus, and Shigella flexneri. Of these strains, a strain P'GW50-2 from pickled scallion with most desirable properties was selected and identified as Lactobacillus plantarum TJ-LP-002. Antimicrobial activity of L. plantarum TJ-LP-002 showed relatively wide range of inhibition spectrum against Gram negative bacteria such as Aeromicrobium hydrophila, E. coli, Pseudomonas, Salmonella, Shigella, and some Gram positive bacteria such as Bacillus cereus, Staphylococcus aureus, Clostridium perfringens, and Propionibacterium.

Development of a Label-Free LC-MS/MS-Based Glucosylceramide Synthase Assay and Its Application to Inhibitors Screening for Ceramide-Related Diseases

  • Fu, Zhicheng;Yun, So Yoon;Won, Jong Hoon;Back, Moon Jung;Jang, Ji Min;Ha, Hae Chan;Lee, Hae Kyung;Shin, In Chul;Kim, Ju Yeun;Kim, Hee Soo;Kim, Dae Kyong
    • Biomolecules & Therapeutics
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    • v.27 no.2
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    • pp.193-200
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    • 2019
  • Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z $588.6{\rightarrow}264.4$ for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625-160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.

Pyruvate Dehydrogenase Kinase Protects Dopaminergic Neurons from Oxidative Stress in Drosophila DJ-1 Null Mutants

  • Lee, Yoonjeong;Kim, Jaehyeon;Kim, Hyunjin;Han, Ji Eun;Kim, Sohee;Kang, Kyong-hwa;Kim, Donghoon;Kim, Jong-Min;Koh, Hyongjong
    • Molecules and Cells
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    • v.45 no.7
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    • pp.454-464
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    • 2022
  • DJ-1 is one of the causative genes of early-onset familial Parkinson's disease (PD). As a result, DJ-1 influences the pathogenesis of sporadic PD. DJ-1 has various physiological functions that converge to control the levels of intracellular reactive oxygen species (ROS). Based on genetic analyses that sought to investigate novel antioxidant DJ-1 downstream genes, pyruvate dehydrogenase (PDH) kinase (PDK) was demonstrated to increase survival rates and decrease dopaminergic (DA) neuron loss in DJ-1 mutant flies under oxidative stress. PDK phosphorylates and inhibits the PDH complex (PDC), subsequently downregulating glucose metabolism in the mitochondria, which is a major source of intracellular ROS. A loss-of-function mutation in PDK was not found to have a significant effect on fly development and reproduction, but severely ameliorated oxidative stress resistance. Thus, PDK plays a critical role in the protection against oxidative stress. Loss of PDH phosphatase (PDP), which dephosphorylates and activates PDH, was also shown to protect DJ-1 mutants from oxidative stress, ultimately supporting our findings. Further genetic analyses suggested that DJ-1 controls PDK expression through hypoxia-inducible factor 1 (HIF-1), a transcriptional regulator of the adaptive response to hypoxia and oxidative stress. Furthermore, CPI-613, an inhibitor of PDH, protected DJ-1 null flies from oxidative stress, suggesting that the genetic and pharmacological inhibition of PDH may be a novel treatment strategy for PD associated with DJ-1 dysfunction.

Recovery of Ammonia Nitrogen using Gas-permeable Membranes (기체투과막을 이용한 암모니아성 질소 회수방안)

  • Lee, Sang-hun;Chae, Sang Yeop
    • Membrane Journal
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    • v.32 no.3
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    • pp.191-197
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    • 2022
  • Ammonia nitrogen can be effectively recovered from livestock manure waste, etc. by using the gas permeable membrane technology. In this case, ammonia gas in the waste passes through the pores in one-side of membrane, impregnated in waste, and then reach the opposite side of the membrane. The permeated ammonia gas molecules are captured and recovered by acid (such as sulfuric acid) in the solution existing on the opposite side of the membrane. In order to improve ammonia nitrogen removals in the inlet part, high pH should be maintained in the feed waste including ammonia nitrogen to recover, which requires the cost of the chemical. To resolve this issue, previous studies tested various methods, for example, utilization of cheap calcium hydroxide or aeration together with inhibition of unwanted nitrification. The gas permeable membranes used for the recovery of ammonia nitrogen may be characterized, not only by proper heat and chemical resistance, but also by hydrophobicity, allowing selective ammonia gas permeation through the hydrophobic membrane pores. Future research should consider the relevant pilot or upscale processes using on-site wastes with various properties, and identify the optimal design/operation conditions as well as economic feasibility improvement plans.

Selective cytotoxicity of a novel mitochondrial complex I inhibitor, YK-135, against EMT-subtype gastric cancer cell lines due to impaired glycolytic capacity

  • Yeojin, Sung;Seungbin, Cha;Sang Bum, Kim;Hakhyun, Kim;Seonghwi, Choi;Sejin, Oh;Minseo, Kim;Yunji, Lee;Gino, Kwon;Jooyoung, Lee;Joo-Youn, Lee;Gyoonhee, Han;Hyun Seok, Kim
    • BMB Reports
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    • v.55 no.12
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    • pp.645-650
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    • 2022
  • Epithelial-to-mesenchymal transition (EMT)-subtype gastric cancers have the worst prognosis due to their higher recurrence rate, higher probability of developing metastases and higher chemo-resistance compared to those of other molecular subtypes. Pharmacologically actionable somatic mutations are rarely found in EMT-subtype gastric cancers, limiting the utility of targeted therapies. Here, we conducted a high-throughput chemical screen using 37 gastric cancer cell lines and 48,467 synthetic small-molecule compounds. We identified YK-135, a small-molecule compound that showed higher cytotoxicity toward EMT-subtype gastric cancer cell lines than toward non-EMT-subtype gastric cancer cell lines. YK-135 exerts its cytotoxic effects by inhibiting mitochondrial complex I activity and inducing AMP-activated protein kinase (AMPK)-mediated apoptosis. We found that the lower glycolytic capacity of the EMT-subtype gastric cancer cells confers synthetic lethality to the inhibition of mitochondrial complex I, possibly by failing to maintain energy homeostasis. Other well-known mitochondrial complex I inhibitors (e.g., rotenone and phenformin) mimic the efficacy of YK-135, supporting our results. These findings highlight mitochondrial complex I inhibitors as promising therapeutic agents for EMT-subtype gastric cancers and YK-135 as a novel chemical scaffold for further drug development.

Fine Mapping of Zenith Derived Rice Stripe Virus Resistance Gene, Stv-b

  • Sais-Beul Lee;Jun-Hyun Cho;Nkulu Rolly Kabange;Sumin Jo;Ji-Yoon Lee;Yeongho Kwon;Ju-Won Kang;Dongjin Shin;Jong-Hee Lee;You-Cheon Song;Jong-Min Ko;Dong-Soo Park
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2020.12a
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    • pp.63-63
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    • 2020
  • Rice stripe virus (RSV) disease is one of the major constraints in rice production, transmitted by the small brown planthopper (SBPH; Laodelphax striatellus). Upon RSV infection, plants develop typical symptoms, which include chlorosis and weakness of newly emerged leaves, white and yellow spots, stripe on leaves, and necrotic and wilting leaves, resulting in plant growth inhibition, oxidative damage that may culminate in programmed cell death (PCD) and plant death in severe epidemics. Although RSV-resistant quantitative trait loci (QTLs), Stv-a, Stv-b, and Stv-bi, were mapped using various resistant varieties, one RSV-resistant gene, OsSOT1, has been identified so far. In this study, we used the rice cultivar Zenith, known to carry Stv-b, to investigate novel RSV-genes through fine mapping. Therefore, we crossed Zenith (Donor parent, RSV resistant) with Ilpum (Recurrent parent, RSV susceptible) to fine-map using a BC2F2 population of 2100 plants. Chromosome segment introgression lines that were heterozygous at a different region were selected, two types of heterozygous lines showed an heterozygous genotype between Sid2 and Sid75 to Indel9 and RM6680. Interestingly, we identified qSTV11Z region harboring Stv-b, covering about 171-kb region between the InDel markers Sid75 and Indel8. The localization of qSTV11Z provides useful information that could be used for marker-assisted selection and determination of genetic resources in rice breeding.

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Hydroxychavicol Inhibits In Vitro Osteoclastogenesis via the Suppression of NF-κB Signaling Pathway

  • Sirada Srihirun;Satarat Mathithiphark;Chareerut Phruksaniyom;Pitchanun Kongphanich;Wisutthaporn Inthanop;Thanaporn Sriwantana;Salunya Tancharoen;Nathawut Sibmooh;Pornpun Vivithanaporn
    • Biomolecules & Therapeutics
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    • v.32 no.2
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    • pp.205-213
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    • 2024
  • Hydroxychavicol, a primary active phenolic compound of betel leaves, previously inhibited bone loss in vivo by stimulating osteogenesis. However, the effect of hydroxychavicol on bone remodeling induced by osteoclasts is unknown. In this study, the anti-osteoclastogenic effects of hydroxychavicol and its mechanism were investigated in receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclasts. Hydroxychavicol reduced the number of tartrate resistance acid phosphatase (TRAP)-positive multinucleated, F-actin ring formation and bone-resorbing activity of osteoclasts differentiated from RAW264.7 cells in a concentration-dependent manner. Furthermore, hydroxychavicol decreased the expression of osteoclast-specific genes, including cathepsin K, MMP-9, and dendritic cell-specific transmembrane protein (DC-STAMP). For mechanistic studies, hydroxychavicol suppressed RANKL-induced expression of major transcription factors, including the nuclear factor of activated T-cells 1 (NFATc1), c-Fos, and c-Jun. At the early stage of osteoclast differentiation, hydroxychavicol blocked the phosphorylation of NF-κB subunits (p65 and Iκβα). This blockade led to the decrease of nuclear translocation of p65 induced by RANKL. In addition, the anti-osteoclastogenic effect of hydroxychavicol was confirmed by the inhibition of TRAP-positive multinucleated differentiation from human peripheral mononuclear cells (PBMCs). In conclusion, hydroxychavicol inhibits osteoclastogenesis by abrogating RANKL-induced NFATc1 expression by suppressing the NF-κB signaling pathway in vitro.

Resistance Activity of Kyung-Ok-Ko on Thermal Stress in C. elegans (경옥고(瓊玉膏)의 열 스트레스에 의한 피부노화 억제 활성)

  • Won-Seok Jung;Sung-Young Cho;Hyun-Woo Cho;Hee-Woon Lee;Young‐IL Jeong;Hee-Taek Kim;Young-Bob Yu
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.37 no.1
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    • pp.17-28
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    • 2024
  • Objectives : This study was conducted to reveal the scientific mechanism of the anti-skin aging activity of Kyung-Ok-Ko(KOK), which is highly useful as a Korean traditional medicine and functional food. Methods : The skin wrinkle and aging inhibitory activity of KOK was confirmed through in vitro experiments of human dermal fibroblast neonatal cell(HDFn) and in vivo of C. elegans, and hairless mouse(SKH-1). Results : The amount of the C-terminus of the collagen precursor in the HDFn cell culture medium treated with KOK using an enzymes-linked immunoassay kit. The group treated with KOK 200㎍/㎖ was a 28.3% increase of collagen precursor compared to the control group. KOK showed inhibitory activity of MMP-1 compared to the control group at a concentration of 200㎍/㎖. In addition, KOK 200㎍/㎖ showed significant inhibitory activity of thermal stress and an oxidative stress compared to the control group in C. elegans. Furthermore, KOK showed a concentration-dependent(100mg/kg and 500mg/kg) anti-wrinkle formation effect in UV-irradiated hairless mouse(SKH-1). Additionally, when KOK was administered to UV-irradiated hairless mice, an increase in procollagen -1 and -3 genes expression was observed, and mmp-1 and mmp-9 genes, which increase collagen decomposition, decreased with the administration of KOK. Conclusions : The skin aging inhibition mechanism of Kyung-Ok-Ko(KOK) is presumed to be achieved through suppressing thermal stress and oxidative stress, suppressing mmp-1 and mmp-9 genes, and increasing procollagen-1 and procollagen-3.

Characteristics of Chloride Ion Behavior in an Cement Matrix Using Calcium Nitrite Inhibitor (아질산칼슘 방청제를 사용한 시멘트 경화체 내의 염소이온 거동 특성)

  • Min-Cheol Shin;Ki-Yong Ann
    • Journal of the Korean Recycled Construction Resources Institute
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    • v.12 no.2
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    • pp.206-213
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    • 2024
  • The present study concerns the inhibition of Calcium Nitrite Inhibitor(Ca(NO2)2) in mortar contaminated by chloride ions. Thus, the corrosion resistance and chloride transport were measured for the mortar containing calcium nitrite inhibitor. As a result, an increase in the dosage of calcium nitrite inhibitor resulted in an increase in the chloride threshold concentration for reinforcement corrosion, while the rate of chloride transport was accelerated. However, the calcium nitrite inhibitor could not guarantee the time to corrosion, due to the increased mobility of chlorides. To ensure the passivity of steel, the dosage of calcium nitrite inhibitor must exceed a certain dosage, ranging from 2.0~3.0 % by cement weight.

In vitro safety and efficacy of probiotics mixture on carbohydrate digestion inhibition (프로바이오틱스 혼합물의 in vitro에서의 안전성 및 탄수화물 소화 저해 효능 평가)

  • Eunsol Seo;Jang-Bin Woo;MinYeong Seo;Jeongmin Woo
    • Food Science and Preservation
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    • v.30 no.3
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    • pp.538-545
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    • 2023
  • This study aimed to assess the in vitro safety of a probiotics mixture (Lactobacillus acidophilus PBS066, Lactiplantibacillus plantarum PBS067, and Limosilactobacillus reuteri PBS072), along with its inhibitory effect on carbohydrate digestion. All three strains met the antibiotic resistance profile of the European Food Safety Authority (EFSA) guidelines. None of the strains exhibited hemolytic activity or cytotoxicity against Caco-2 cells. Strains PBS067 and PBS072 inhibited α-amylase activity, whereas all three strains suppressed α-glucosidase activity, indicating that the mixture might limit carbohydrate digestion in the gastrointestinal tract. These findings support the safety of this probiotics mixture and its potential to modulate carbohydrate metabolism in the gut.