• Title/Summary/Keyword: Multi-Omics

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DC23, a Triazolothione Resorcinol Analogue, Is Extensively Metabolized to Glucuronide Conjugates in Human Liver Microsomes

  • Shon, Jong Cheol;Joo, Jeongmin;Lee, Taeho;Kim, Nam Doo;Liu, Kwang-Hyeon
    • Mass Spectrometry Letters
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    • v.9 no.1
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    • pp.24-29
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    • 2018
  • DC23, a triazolothione resorcinol analogue, is known to inhibit heat shock protein 90 and pyruvate dehydrogenase kinase which are up-regulated in cancer and diabetes, respectively. This study was performed to elucidate the metabolism of DC23 in human liver microsomes (HLMs). HLMs incubated with DC23 in the presence of uridine 5'-diphosphoglucuronic acid (UDPGA) and/or ${\beta}$-nicotinamide adenine dinucleotide phosphate (NADPH) resulted in the formation of four metabolites, M1-M4. M1 was identified as DC23-N-Oxide, on the basis of LC-MS/MS analysis. DC23 was further metabolized to its glucuronide conjugates (M2, M3, and M4). In vitro metabolic stability studies conducted with DC23 in HLMs revealed significant glucuronide conjugation with a $t_{1/2}$ value of 1.3 min. The inhibitory potency of DC23 on five human cytochrome P450s was also investigated in HLMs. In these experiments, DC23 inhibited CYP2C9-mediated tolbutamide hydroxylase activity with an $IC_{50}$ value of $8.7{\mu}M$, which could have implications for drug interactions.

Emerging role of RUNX3 in the regulation of tumor microenvironment

  • Manandhar, Sarala;Lee, You Mie
    • BMB Reports
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    • v.51 no.4
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    • pp.174-181
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    • 2018
  • A number of genes have been therapeutically targeted to relieve cancer, but cancer relapse is still a growing issue. The concept that the surrounding tumor environment is critical for the progression of cancer may foster an answer to the issue of cancer malignancy. Runt domain transcription factors (RUNX1, 2, and 3) are evolutionarily conserved and have been intensively studied for their roles in normal development and pathological conditions. During tumor growth, a hypoxic microenvironment and infiltration of the tumor by immune cells are common phenomena. In this review, we briefly introduce the consequences of hypoxia and immune cell infiltration into the tumor microenvironment with a focus on RUNX3 as a critical regulator. Furthermore, based on our current knowledge of the functional role of RUNX3 in hypoxia and immune cell maintenance, a probable therapeutic intervention is suggested for the effective management of tumor growth and malignancy.

Cancer driver gene using multi-omics data and biological network information (멀티 오믹스 데이터 및 생물학적 네트워크 정보를 이용한 드라이버 유전자 분류)

  • Jeong-Ho Park;Kyuri Jo
    • Annual Conference of KIPS
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    • 2023.05a
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    • pp.490-492
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    • 2023
  • 시퀀싱(sequencing) 기술의 발달로 다양한 오믹스(omics) 데이터의 축적과 인공 지능 기술의 발달로 인하여 다양한 드라이버 유전자 분류기법이 제안되어왔다. 최근에는 암 데이터가 대용량으로 축적되며 기계 학습 기반의 다양한 기법들이 활발히 제안되었다. 특히 다양한 오믹스 데이터를 결합한 고차원 데이터에서 높은 정확도를 확보하기 위한 시도가 활발히 이루어지고 있다. 본 논문에서는 멀티 오믹스와 네트워크 관련 특징을 기반으로 암의 증식 및 발생에 중요한 역할을 하는 드라이버 유전자를 분류하는 딥러닝 모델을 제시한다. 또한 The Cancer Genome Atlas(TCGA) 데이터를 통해서 모델 학습 후 기존 통계 및 머신러닝 기반 기법과 비교하여 성능이 개선되었음을 확인하였다.

Seed-borne Pathogenic Bacterium Interact with Air-borne Plant Pathogenic Fungus in Rice Fields

  • Jung, Boknam;Park, Jungwook;Kim, Namgyu;Li, Taiying;Kim, Soyeon;Bartley, Laura E.;Kim, Jinnyun;Kim, Inyoung;Kang, Yoonhee;Yun, Ki-Hoon;Choi, Younghae;Lee, Hyun-Hee;Lee, Kwang Sik;Kim, Bo Yeon;Shon, Jong Cheol;Kim, Won Cheol;Liu, Kwang-Hyeon;Yoon, Dahye;Kim, Suhkman;Ji, Sungyeon;Seo, Young Su;Lee, Jungkwan
    • 한국균학회소식:학술대회논문집
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    • 2018.05a
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    • pp.33-33
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    • 2018
  • Air-borne plant pathogenic fungus Fusarium graminearum and seed-borne plant pathogenic bacterium Burkholderia glumae are cause similar disease symptoms in rice heads. Here we showed that two pathogens frequently co-isolated in rice heads and F. graminearum is resistant to toxoflavin produced by B. glumae while other fungal genera are sensitive to the toxin. We have tried to clarify the resistant mechanism of F. graminearum against toxoflavin and the ecological reason of co-existence of the two pathogens in rice. We found that F. graminearum carries resistance to toxoflavin as accumulating lipid in fungal cells. Co-cultivation of two pathogens resulted in increased conidia and enhanced chemical attraction and attachment of the bacterial cells to the fungal conidia. Bacteria physically attached to fungal conidia, which protected bacterium cells from UV light and allowed disease dispersal. Chemotaxis analysis showed that bacterial cells moved toward the fungal exudation compared to a control. Even enhanced the production of phytotoxic trichothecene by the fungal under presence of toxoflavin and disease severity on rice heads was significantly increased by co-inoculation rather than single inoculation. This study suggested that the undisclosed potentiality of air-born infection of bacteria using the fungal spores for survival and dispersal.

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Metabolic Regulation of Longevity and Immune Response in Caenorhabditis elegans by Ingestion of Lacticaseibacillus rhamnosus IDCC 3201 Using Multi-Omics Analysis

  • Daniel Junpyo Lee;Ju Young Eor;Min-Jin Kwak;Junbeom Lee;An Na Kang;Daye Mun;Hyejin Choi;Minho Song;Jong Nam Kim;Jun-Mo Kim;Jungwoo Yang;Hyung Wook Kim;Sangnam Oh;Younghoon Kim
    • Journal of Microbiology and Biotechnology
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    • v.34 no.5
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    • pp.1109-1118
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    • 2024
  • Probiotics, specifically Lacticaseibacillus rhamnosus, have garnered attention for their potential health benefits. This study focuses on evaluating the probiotic properties of candidate probiotics L. rhamnosus IDCC 3201 (3201) using the Caenorhabditis elegans surrogate animal model, a well-established in vivo system for studying host-bacteria interactions. The adhesive ability to the host's gastrointestinal tract is a crucial criterion for selecting potential probiotic bacteria. Our findings demonstrated that 3201 exhibits significantly higher adhesive capabilities compared with Escherichia coli OP50 (OP50), a standard laboratory food source for C. elegans and is comparable with the widely recognized probiotic L. rhamnosus GG (LGG). In lifespan assay, 3201 significantly increased the longevity of C. elegans compared with OP50. In addition, preconditioning with 3201 enhanced C. elegans immune response against four different foodborne pathogenic bacteria. To uncover the molecular basis of these effects, transcriptome analysis elucidated that 3201 modulates specific gene expression related to the innate immune response in C. elegans. C-type lectin-related genes and lysozyme-related genes, crucial components of the immune system, showed significant upregulation after feeding 3201 compared with OP50. These results suggested that preconditioning with 3201 may enhance the immune response against pathogens. Metabolome analysis revealed increased levels of fumaric acid and succinic acid, metabolites of the citric acid cycle, in C. elegans fed with 3201 compared with OP50. Furthermore, there was an increase in the levels of lactic acid, a well-known antimicrobial compound. This rise in lactic acid levels may have contributed to the robust defense mechanisms against pathogens. In conclusion, this study demonstrated the probiotic properties of the candidate probiotic L. rhamnosus IDCC 3201 by using multi-omics analysis.

Application of Iipidomics in food science (식품분야에서 Iipidomics 분석 기술의 활용)

  • Kim, Hyun-Jin;Jang, Gwang-Ju;Lee, Hyeon-Jeong;Kim, Bo-Min;Oh, Juhong
    • Food Science and Industry
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    • v.50 no.1
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    • pp.16-25
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    • 2017
  • There is no doubt that accumulation of big data using multi-omics technologies will be useful to solve human's long-standing problems such as development of personalized diet and medicine, overcoming diseases, and longevity. However, in the food industry, big data based on omics is scarcely accumulated. In particular, comprehensive analysis of molecular lipid metabolites directly associated with food quality, such as taste, flavor, and texture has been very limited. Moreover, most of food lipidomics studies are applied to analyze lipid components and discriminate authenticity and freshness of limited foods including vegetable and fish oil. However, if lipid big data through food lipidomics research of various foods and materials can be accumulated, lipidomics can be used in the optimization of food processing, production, delivery system, food safety, and storage as well as functional food.

Single-Cell Toolkits Opening a New Era for Cell Engineering

  • Lee, Sean;Kim, Jireh;Park, Jong-Eun
    • Molecules and Cells
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    • v.44 no.3
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    • pp.127-135
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    • 2021
  • Since the introduction of RNA sequencing (RNA-seq) as a high-throughput mRNA expression analysis tool, this procedure has been increasingly implemented to identify cell-level transcriptome changes in a myriad of model systems. However, early methods processed cell samples in bulk, and therefore the unique transcriptomic patterns of individual cells would be lost due to data averaging. Nonetheless, the recent and continuous development of new single-cell RNA sequencing (scRNA-seq) toolkits has enabled researchers to compare transcriptomes at a single-cell resolution, thus facilitating the analysis of individual cellular features and a deeper understanding of cellular functions. Nonetheless, the rapid evolution of high throughput single-cell "omics" tools has created the need for effective hypothesis verification strategies. Particularly, this issue could be addressed by coupling cell engineering techniques with single-cell sequencing. This approach has been successfully employed to gain further insights into disease pathogenesis and the dynamics of differentiation trajectories. Therefore, this review will discuss the current status of cell engineering toolkits and their contributions to single-cell and genome-wide data collection and analyses.

Discovery to Human Disease Research: Proteo-Metabolomics Analysis

  • Minjoong Joo;Jeong-Hun Mok;Van-An Duong;Jong-Moon Park;Hookeun Lee
    • Mass Spectrometry Letters
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    • v.15 no.2
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    • pp.69 -78
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    • 2024
  • The advancement of high-throughput omics technologies and systems biology is essential for understanding complex biological mechanisms and diseases. The integration of proteomics and metabolomics provides comprehensive insights into cellular functions and disease pathology, driven by developments in mass spectrometry (MS) technologies, including electrospray ionization (ESI). These advancements are crucial for interpreting biological systems effectively. However, integrating these technologies poses challenges. Compared to genomic, proteomics and metabolomics have limitations in throughput, and data integration. This review examines developments in MS equipped electrospray ionization (ESI), and their importance in the effective interpretation of biological mechanisms. The review also discusses developments in sample preparation, such as Simultaneous Metabolite, Protein, Lipid Extraction (SIMPLEX), analytical techniques, and data analysis, highlighting the application of these technologies in the study of cancer or Huntington's disease, underscoring the potential for personalized medicine and diagnostic accuracy. Efforts by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and integrative data analysis methods such as O2PLS and OnPLS extract statistical similarities between metabolomic and proteomic data. System modeling techniques that mathematically explain and predict system responses are also covered. This practical application also shows significant improvements in cancer research, diagnostic accuracy and therapeutic targeting for diseases like pancreatic ductal adenocarcinoma, non-small cell lung cancer, and Huntington's disease. These approaches enable researchers to develop standardized protocols, and interoperable software and databases, expanding multi-omics research application in clinical practice.

Investigation of Herb-Drug Interactions between Korean Red Ginseng Extract and five CYP Substrates by LC-MS/MS

  • Jo, Jung Jae;Lee, Sangkyu
    • Mass Spectrometry Letters
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    • v.8 no.4
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    • pp.98-104
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    • 2017
  • Ginseng (Panax ginseng Meyer) is a well-known health functional food used as a traditional herbal drug in Asian countries owing to its diverse pharmacological effects. Herb-drug interactions may cause unexpected side effects of co-administered drugs by the alteration of pharmacokinetics through effects on cytochrome P450 activity. In this study, we investigated the herb-drug interactions between Korean red ginseng extract (KRG) and five CYP-specific probes in mice. The pharmacokinetics of KRG extract induced-drug interactions were studied by cassette dosing of five CYP substrates for CYP1A, 2B, 2C, 2D, and 3A and the LC-MS/MS analysis of the blood concentration of metabolites of each of the five probes. The linearity, precision, and accuracy of the quantification method of the five metabolites were successfully confirmed. The plasma concentrations of five metabolites after co-administration of different doses of the KRG extract (0, 0.5, 1, and 2 g/kg) were quantified by LC-MS/MS and dose-dependent pharmacokinetic parameters were determined. The pharmacokinetic parameters of the five metabolites were not significantly altered by the dose of the KRG extract. In conclusion, the single co-administration of KRG extract up to 2 g/kg in vivo did not cause any significant herb-drug interactions linked to the modulation of CYP activity.

Analysis of polyethoxylated ascorbic acid using spectrophotometry (분광광도계를 이용한 폴리에톡시레이티드 아스코르빈산 분석법 개발)

  • Wu, Zhexue;Liu, Kwang-Hyeon
    • Journal of Applied Biological Chemistry
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    • v.59 no.4
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    • pp.361-364
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    • 2016
  • We developed a spectrophotometric assay method for polyethoxylated ascorbic acidusing 3-ethyl ascorbic acid as standard material. The analytical method was validated by linearity, accuracy, precision, and stability. The coefficient of variation of the precision of the assay was less than 3.4 %. The linearity of the calibration curves in the desired concentration range is good ($r^2$>0.998). 3-Ethyl ascorbic acid and polyethoxylated ascorbic acid were stable in stock solution at room temperature for up to at least 6 h. The developed assay could be used for the content analysis of polyethoxylated ascorbic acid in samples.