• Title/Summary/Keyword: metabolic network

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Effects of Scutellariae Radix on Gene Expression of Human Cervical Cancer Cells(SNU-703) (황금추출물이 인간 유래 자궁경부암세포의 유전자발현에 미치는 영향)

  • Jo, Hyun-Jung;Gu, Hee-Jun;Cho, Seong-Hee;Park, Kyung-Mi;Yang, Seung-Jeong
    • The Journal of Korean Obstetrics and Gynecology
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    • v.22 no.3
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    • pp.117-134
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    • 2009
  • Purpose: In the theory of traditional medicine, Scutellariae Radix (SR) can clear away heat and remove dampness, purge the sthenic fire and remove toxic materials, cool blood and stop bleeding to prevent miscarriage. Recently, SR is known to have anti-cancer activity. For this reason, the present author designed to investigate the effect of SR on proliferation rates of cervical cancer cell line, then effects on genetic profile by SR. Methods: The genetic profile for the effect of SR on human derived cervical cancer cell line, SNU-703, was measured using microarray technique, and the functional analysis on these genes was conducted. Results: Total 519 genes were up-regulated and 606 genes down-regulated in cells treated with SR. Genes induced or suppressed by SR were all mainly concerned with metabolic process, regulation of biological process and protein binding. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as TNFRSF1A, AKT1, MAPK3, and STAT3 that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of SR as anti-cancer drug and also suggest that related mechanisms are involved in TNFRSF1A, AKT1, MAPK3, and STAT3 related signalling pathways.

Harnessing the Power of IL-7 to Boost T Cell Immunity in Experimental and Clinical Immunotherapies

  • Jung-Hyun Park;Seung-Woo Lee;Donghoon Choi;Changhyung Lee;Young Chul Sung
    • IMMUNE NETWORK
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    • v.24 no.1
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    • pp.9.1-9.21
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    • 2024
  • The cytokine IL-7 plays critical and nonredundant roles in T cell immunity so that the abundance and availability of IL-7 act as key regulatory mechanisms in T cell immunity. Importantly, IL-7 is not produced by T cells themselves but primarily by non-lymphoid lineage stromal cells and epithelial cells that are limited in their numbers. Thus, T cells depend on cell extrinsic IL-7, and the amount of in vivo IL-7 is considered a major factor in maximizing and maintaining the number of T cells in peripheral tissues. Moreover, IL-7 provides metabolic cues and promotes the survival of both naïve and memory T cells. Thus, IL-7 is also essential for the functional fitness of T cells. In this regard, there has been an extensive effort trying to increase the protein abundance of IL-7 in vivo, with the aim to augment T cell immunity and harness T cell functions in anti-tumor responses. Such approaches started under experimental animal models, but they recently culminated into clinical studies, with striking effects in re-establishing T cell immunity in immunocompromised patients, as well as boosting anti-tumor effects. Depending on the design, glycosylation, and the structure of recombinantly engineered IL-7 proteins and their mimetics, recombinant IL-7 molecules have shown dramatic differences in their stability, efficacy, cellular effects, and overall immune functions. The current review is aimed to summarize the past and present efforts in the field that led to clinical trials, and to highlight the therapeutical significance of IL-7 biology as a master regulator of T cell immunity.

Comprehensive Lipid Profiling Recapitulates Enhanced Lipolysis and Fatty Acid Metabolism in Intimal Foamy Macrophages From Murine Atherosclerotic Aorta

  • Jae Won Seo;Kyu Seong Park;Gwang Bin Lee;Sang-eun Park;Jae-Hoon Choi;Myeong Hee Moon
    • IMMUNE NETWORK
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    • v.23 no.4
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    • pp.28.1-28.20
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    • 2023
  • Lipid accumulation in macrophages is a prominent phenomenon observed in atherosclerosis. Previously, intimal foamy macrophages (FM) showed decreased inflammatory gene expression compared to intimal non-foamy macrophages (NFM). Since reprogramming of lipid metabolism in macrophages affects immunological functions, lipid profiling of intimal macrophages appears to be important for understanding the phenotypic changes of macrophages in atherosclerotic lesions. While lipidomic analysis has been performed in atherosclerotic aortic tissues and cultured macrophages, direct lipid profiling has not been performed in primary aortic macrophages from atherosclerotic aortas. We utilized nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry to provide comprehensive lipid profiles of intimal non-foamy and foamy macrophages and adventitial macrophages from Ldlr-/- mouse aortas. We also analyzed the gene expression of each macrophage type related to lipid metabolism. FM showed increased levels of fatty acids, cholesterol esters, phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol, and sphingomyelin. However, phosphatidylethanolamine, phosphatidic acid, and ceramide levels were decreased in FM compared to those in NFM. Interestingly, FM showed decreased triacylglycerol (TG) levels. Expressions of lipolysis-related genes including Pnpla2 and Lpl were markedly increased but expressions of Lpin2 and Dgat1 related to TG synthesis were decreased in FM. Analysis of transcriptome and lipidome data revealed differences in the regulation of each lipid metabolic pathway in aortic macrophages. These comprehensive lipidomic data could clarify the phenotypes of macrophages in the atherosclerotic aorta.

The cooperative regulatory effect of the miRNA-130 family on milk fat metabolism in dairy cows

  • Xiaofen Li;Yanni Wu;Xiaozhi Yang;Rui Gao;Qinyue Lu;Xiaoyang Lv;Zhi Chen
    • Animal Bioscience
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    • v.37 no.7
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    • pp.1289-1302
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    • 2024
  • Objective: There is a strong relationship between the content of beneficial fatty acids in milk and milk fat metabolic activity in the mammary gland. To improve milk quality, it is therefore necessary to study fatty acid metabolism in bovine mammary gland tissue. In adipose tissue, peroxisome proliferator-activated receptor gamma (PPARG), the core transcription factor, regulates the fatty acid metabolism gene network and determines fatty acid deposition. However, its regulatory effects on mammary gland fatty acid metabolism during lactation have rarely been reported. Methods: Transcriptome sequencing was performed during the prelactation period and the peak lactation period to examine mRNA expression. The significant upregulation of PPARG drew our attention and led us to conduct further research. Results: According to bioinformatics prediction, dual-luciferase reporter system detection, real-time quantitative reverse transcription polymerase chain reaction and Western blotting, miR-130a and miR-130b could directly target PPARG and inhibit its expression. Furthermore, triglyceride and oil red O staining proved that miR-130a and miR-130b inhibited milk fat metabolism in bovine mammary epithelial cells (BMECs), while PPARG promoted this metabolism. In addition, we also found that the coexpression of miR-130a and miR-130b significantly enhanced their ability to regulate milk fat metabolism. Conclusion: In conclusion, our findings indicated that miR-130a and miR-130b could target and repress PPARG and that they also have a functional superposition effect. miR-130a and miR-130b seem to synergistically regulate lipid catabolism via the control of PPARG in BMECs. In the long-term, these findings might be helpful in developing practical means to improve high-quality milk.

Systems Pharmacological Analysis of Dichroae Radix in Anti-Tumor Metastasis Activity (시스템 약리학적 분석에 의한 상산의 암전이 억제 효과)

  • Jee Ye Lee;Ah Yeon Shin;Hak Koon Kim;Won Gun An
    • Herbal Formula Science
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    • v.31 no.4
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    • pp.295-313
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    • 2023
  • Objectives : While treatments for cancer are advancing, the development of effective treatments for cancer metastasis, the main cause of cancer patient death, remains insufficient. Recent studies on Dichroae Radix have revealed that its active ingredients have the potential to inhibit cancer metastasis. This study aimed to investigate the cancer metastasis inhibitory effect of Dichroae Radix using network pharmacological analysis. Methods : The active compounds of Dichroae Radix have been identified using Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The UniProt database was used to collect each of information of all target proteins associated with the active compounds. To find the bio-metabolic processes associated with each target, the DAVID6.8 Gene Functional classifier tool was used. Compound-Target and Target-Pathway networks were analyzed via Cytoscape 3.40. Results : In total, 25 active compounds and their 62 non-redundant targets were selected through the TCMSP database and analysis platform. The target genes underwent gene ontology and pathway enrichment analysis. The gene list applied to the gene ontology analysis revealed associations with various biological processes, including signal transduction, chemical synaptic transmission, G-protein-coupled receptor signaling pathways, response to xenobiotic stimulus, and response to drugs, among others. A total of eleven genes, including HSP90AB1, CALM1, F2, AR, PAKACA, PTGS2, NOS2, RXRA, ESR1, ESR2, and NCOA1, were found to be associated with biological pathways related to cancer metastasis. Furthermore, nineteen of the active compounds from Dichroae Radix were confirmed to interact with these genes. Conclusions : The results provide valuable insights into the mechanism of action and molecular targets of Dichroae Radix. Notably, Berberine, the main active ingredient of Dichroae Radix, plays a significant role in degrading AR proteins in advanced prostate cancer. Further studies and validations can provide crucial data to advance cancer metastasis prevention and treatment strategies.

International Digestive Endoscopy Network consensus on the management of antithrombotic agents in patients undergoing gastrointestinal endoscopy

  • Seung Joo Kang;Chung Hyun Tae;Chang Seok Bang;Cheol Min Shin;Young-Hoon Jeong;Miyoung Choi;Joo Ha Hwang;Yutaka Saito;Philip Wai Yan Chiu;Rungsun Rerknimitr;Christopher Khor;Vu Van Khien;Kee Don Choi;Ki-Nam Shim;Geun Am Song;Oh Young Lee
    • Clinical Endoscopy
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    • v.57 no.2
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    • pp.141-157
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    • 2024
  • Antithrombotic agents, including antiplatelet agents and anticoagulants, are widely used in Korea because of the increasing incidence of cardiocerebrovascular disease and the aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. The clinical practice guidelines for this issue, developed by the Korean Society of Gastrointestinal Endoscopy, were published in 2020. However, new evidence on the use of dual antiplatelet therapy and direct anticoagulant management has emerged, and revised guidelines have been issued in the United States and Europe. Accordingly, the previous guidelines were revised. Cardiologists were part of the group that developed the guideline, and the recommendations went through a consensus-reaching process among international experts. This guideline presents 14 recommendations made based on the Grading of Recommendations, Assessment, Development, and Evaluation methodology and was reviewed by multidisciplinary experts. These guidelines provide useful information that can assist endoscopists in the management of patients receiving antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.

Time-based Expression Networks of Genes Related to Cold Stress in Brassica rapa ssp. pekinensis (배추의 저온 스트레스 처리 시간대별 발현 유전자 네트워크 분석)

  • Lee, Gi-Ho;Yu, Jae-Gyeong;Park, Young-Doo
    • Horticultural Science & Technology
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    • v.33 no.1
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    • pp.114-123
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    • 2015
  • Plants can respond and adapt to cold stress through regulation of gene expression in various biochemical and physiological processes. Cold stress triggers decreased rates of metabolism, modification of cell walls, and loss of membrane function. Hence, this study was conducted to construct coexpression networks for time-based expression pattern analysis of genes related to cold stress in Chinese cabbage (Brassica rapa ssp. pekinensis). B. rapa cold stress networks were constructed with 2,030 nodes, 20,235 edges, and 34 connected components. The analysis suggests that similar genes responding to cold stress may also regulate development of Chinese cabbage. Using this network model, it is surmised that cold tolerance is strongly related to activation of chitinase antifreeze proteins by WRKY transcription factors and salicylic acid signaling, and to regulation of stomatal movement and starch metabolic processes for systemic acquired resistance in Chinese cabbage. Moreover, within 48 h, cold stress triggered transition from vegetative to reproductive phase and meristematic phase transition. In this study, we demonstrated that this network model could be used to precisely predict the functions of cold resistance genes in Chinese cabbage.

Deep Learning Algorithm and Prediction Model Associated with Data Transmission of User-Participating Wearable Devices (사용자 참여형 웨어러블 디바이스 데이터 전송 연계 및 딥러닝 대사증후군 예측 모델)

  • Lee, Hyunsik;Lee, Woongjae;Jeong, Taikyeong
    • Journal of Korea Society of Industrial Information Systems
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    • v.25 no.6
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    • pp.33-45
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    • 2020
  • This paper aims to look at the perspective that the latest cutting-edge technologies are predicting individual diseases in the actual medical environment in a situation where various types of wearable devices are rapidly increasing and used in the healthcare domain. Through the process of collecting, processing, and transmitting data by merging clinical data, genetic data, and life log data through a user-participating wearable device, it presents the process of connecting the learning model and the feedback model in the environment of the Deep Neural Network. In the case of the actual field that has undergone clinical trial procedures of medical IT occurring in such a high-tech medical field, the effect of a specific gene caused by metabolic syndrome on the disease is measured, and clinical information and life log data are merged to process different heterogeneous data. That is, it proves the objective suitability and certainty of the deep neural network of heterogeneous data, and through this, the performance evaluation according to the noise in the actual deep learning environment is performed. In the case of the automatic encoder, we proved that the accuracy and predicted value varying per 1,000 EPOCH are linearly changed several times with the increasing value of the variable.

Contrast Media Side Effects Prediction Study using Artificial Intelligence Technique (인공지능 기법을 이용한 조영제 부작용 예측 연구)

  • Sang-Hyun Kim
    • Journal of the Korean Society of Radiology
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    • v.17 no.3
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    • pp.423-431
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    • 2023
  • The purpose of this study is to analyze the factors affecting the classification of the severity of contrast media side effects based on the patient's body information using artificial intelligence techniques to be used as basic data to reduce the degree of contrast medium side effects. The data used in this study were 606 examiners who had no contrast medium side effects in the past history survey among 1,235 cases of contrast medium side effects among 58,000 CT scans performed at a general hospital in Seoul. The total data is 606, of which 70% was used as a training set and the remaining 30% was used as a test set for validation. Age, BMI(Body Mass Index), GFR(Glomerular Filtration Rate), BUN(Blood Urea Nitrogen), GGT(Gamma Glutamyl Transgerase), AST(Aspartate Amino Transferase,), and ALT(Alanine Amiono Transferase) features were used as independent variables, and contrast media severity was used as a target variable. AUC(Area under curve), CA(Classification Accuracy), F1, Precision, and Recall were identified through AdaBoost, Tree, Neural network, SVM, and Random foest algorithm. AdaBoost and Random Forest show the highest evaluation index in the classification prediction algorithm. The largest factors in the predictions of all models were GFR, BMI, and GGT. It was found that the difference in the amount of contrast media injected according to renal filtration function and obesity, and the presence or absence of metabolic syndrome affected the severity of contrast medium side effects.

Cardioprotective effect of ginsenoside Rb1 via regulating metabolomics profiling and AMP-activated protein kinase-dependent mitophagy

  • Hu, Jingui;Zhang, Ling;Fu, Fei;Lai, Qiong;Zhang, Lu;Liu, Tao;Yu, Boyang;Kou, Junping;Li, Fang
    • Journal of Ginseng Research
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    • v.46 no.2
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    • pp.255-265
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    • 2022
  • Background: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. Methods: The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Results: Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Conclusions: Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.