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Dynamic ¹³C Flux Analysis Captures the Reorganization of Adipocyte Glucose Metabolism in Response to Insulin (vol 23, 100855, 2020)

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Iscience 2020年第12期23卷 100855页

作者： Quek, Lake-Ee Krycer, James R. Ohno, Satoshi Yugi, Katsuyuki Fazakerley, Daniel J. Scalzo, Richard Elkington, Sarah D. Dai, Ziwei Hirayama, Akiyoshi Ikeda, Satsuki Shoji, Futaba Suzuki, Kumi Locasale, Jason W. Soga, Tomoyoshi James, David E. Kuroda, Shinya Charles Perkins Centre The University of Sydney Sydney NSW 2006 Australia School of Mathematics and Statistics The University of Sydney Sydney NSW 2006 Australia Sydney Medical School The University of Sydney Sydney NSW 2006 Australia Department of Biological Sciences Graduate School of Science University of Tokyo Hongo 7-3-1 Bunkyo-ku Tokyo 113-0033 Japan School of Life and Environmental Sciences The University of Sydney Sydney NSW 2006 Australia Institute for Advanced Biosciences Keio University Tsuruoka Yamagata 997-0052 Japan YCI Laboratory for Trans-Omics Young Chief Investigator Program RIKEN Center for Integrative Medical Sciences 1-7-22 Suehiro-cho Tsurumi-ku Yokohama Kanagawa 230-0045 Japan Faculty of Engineering and Information Technologies The University of Sydney Sydney NSW 2006 Australia Department of Pharmacology and Cancer Biology Duke University School of Medicine Duke University Durham NC 27710 USA AMED-CREST AMED 1-7-1 Otemachi Chiyoda-Ku Tokyo 100-0004 Japan Department of Computational Biology and Medical Sciences Graduate School of Frontier Sciences University of Tokyo 5-1-5 Kashiwanoha Kashiwa Chiba 277-8562 Japan CREST Japan Science and Technology Agency Bunkyo-ku Tokyo 113-0033 Japan

Cellular metabolism is dynamic, but quantifying non-steady metabolic fluxes by stable isotope tracers presents unique computational challenges. Here, we developed an efficient 13 C-tracer dynamic metabolic flux analysis (13C-DMFA) framework for modeling central carbon fluxes that vary over time. We used B-splines to generalize the flux parameterization system and to improve the stability of the optimization algorithm. As proof of concept, we investigated how 3T3-L1 cultured adipocytes acutely metabolize glucose in response to insulin. Insulin rapidly stimulates glucose uptake, but intracellular pathways responded with differing speeds and magnitudes. Fluxes in lower glycolysis increased faster than those in upper glycolysis. Glycolysis fluxes rose disproportionally larger and faster than the tricarboxylic acid cycle, with lactate a primary glucose end product. The uncovered array of flux dynamics suggests that glucose catabolism is additionally regulated beyond uptake to help shunt glucose into appropriate pathways. This work demonstrates the value of using dynamic intracellular fluxes to understand metabolic function and pathway regulation.

关键词： Biological sciences Flux Data Metabolomics Metabolic Flux Analysis

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Implementation of walk-through audits for designing energy management system: A first step towards an efficient campus 3

Implementation of walk-through audits for designing energy m...

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3rd International Conference on Empathic Architecture, ICEA 2019

作者： Yandri, E. Ariati, R. Uyun, A.S. Setyobudi, R.H. Anne, O. Susanto, H. Vincevica-Gaile, Z. Graduate School of Renewable Energy Darma Persada University Jl. Taman Malaka Selatan No. 22 Pondok Kelapa East Jakarta13450 Indonesia Center of Renewable Energy Studies Darma Persada University Jl. Taman Malaka Selatan No. 22 Pondok Kelapa East Jakarta13450 Indonesia Department of Agriculture Science Postgraduate Program University of Muhammadiyah Malang Jl. Raya Tlogomas No. 246 Malang65145 Indonesia Department of Natural Sciences Faculty of Marine Technology and Natural Sciences Klaipeda University Klaipeda92294 Lithuania Department of Mechanical Engineering Darma Persada University Jl. Taman Malaka Selatan No. 22 East Jakarta13450 Indonesia Department of Environmental Science University of Latvia Raina bulvaris 19 Centra rajons RigaLV-1586 Latvia

The purpose of this study is to design a concept of energy management control system (EMCS) at the UNSADA campus, Jakarta, Indonesia by utilizing the results of the previous walkthrough audit. EMCS is an important first step by involving all parties on campus to be concerned the sustainable energy savings. The energy efficiency program utilizes the campus as an energy laboratory to identify, recommend, implement and evaluate the energy consumption, so that the expected energy efficiency targeted by the top managements can be achieved. This program is motivated by several reasons, such as;to support government policies in reducing dependence on fossil energy by implementing energy conservation programs;as a reflection of compliance with the implementation of educational service buildings (including the campus in Jakarta);a vision as the efficient campus in energy consumption that has been determined by the campus management. To achieve these goals, there are four stages to be done;the preparation, the conducting audit, the audit analysis, and the recommendation for implementation. The results provide an overview of the opportunities to save the energy consumption and to develop EMCS by involving all stack-holders on campus. © 2020 Published under licence by IOP Publishing Ltd.

关键词： Energy utilization

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Mediation analysis for TNF-α as a mediator between multiple metal exposure and kidney function

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Ecotoxicology and environmental safety 2024年 283卷 116837页

作者： Kuei-Hau Luo Hung-Pin Tu Huang-Chih Chang Chen-Cheng Yang Wei-Chun Weng Tzu-Hua Chen Cheng-Hong Yang Hung-Yi Chuang Graduate Institute of Medicine College of Medicine Kaohsiung Medicine University Kaohsiung City 807 Taiwan. Department of Public Health and Environmental Medicine School of Medicine College of Medicine Kaohsiung Medical University Kaohsiung 807 Taiwan. Divisions of Pulmonary & Critical Care Medicine Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan. Graduate Institute of Medicine College of Medicine Kaohsiung Medicine University Kaohsiung City 807 Taiwan Department of Occupational Medicine Kaohsiung Municipal Siaogang Hospital Kaohsiung Medical University Kaohsiung 812 Taiwan. Division of Gastroenterology Department of Internal Medicine Kaohsiung Armed Forces General Hospital Kaohsiung 802 Taiwan. Department of Family Medicine Kaohsiung Municipal Ta-Tung Hospital Kaohsiung 801 Taiwan. Department of Information Management Tainan University of Technology Tainan 71002 Taiwan Department of Electronic Engineering National Kaohsiung University of Science and Technology Kaohsiung 80778 Taiwan. Department of Public Health and Environmental Medicine School of Medicine College of Medicine Kaohsiung Medical University Kaohsiung 807 Taiwan Department of Occupational and Environmental Medicine Kaohsiung Medicine University Hospital Kaohsiung Medicine University Kaohsiung 807 Taiwan Ph.D. Program in Environmental and Occupational Medicine College of Medicine and Research Center for Precision Environmental Medicine Kaohsiung Medical University Kaohsiung 807 Taiwan. Electronic address: ericch@kmu.edu.tw.

The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = -0.021, p = 0.011), Pb (coefficients = -0.060, p < 0.001), and Zn (coefficients = -0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p < 0.001). This study suggested that TNF-α may be a persuasive pathway mediating the association between metals and kidney function. Inflammation and kidney injury could be the underlying mechanisms of metal exposure. However, there i

关键词： Kidney function Mediation analysis Metals Pb TNF-α

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Electronic nose in differentiating and ascertaining clinical status among patients with pulmonary nontuberculous mycobacteria: A prospective multicenter study

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The Journal of infection 2023年第3期87卷 255-258页

作者： Meng-Rui Lee Hung-Ling Huang Wei-Chang Huang Shang-Yu Wu Pang-Chun Liu Jui-Ching Wu Meng-Hsuan Cheng Chau-Chyun Sheu Kea-Tiong Tang Jann-Yuan Wang Chao-Chi Ho Jin-Yuan Shih Inn-Wen Chong Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan. Department of Internal Medicine Kaohsiung Municipal Ta-Tung Hospital Kaohsiung Taiwan Division of Pulmonary and Critical Care Medicine Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taiwan Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan. Division of Chest Medicine Department of Internal Medicine Taichung Veterans General Hospital Taichung Taiwan Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan Mycobacteria Center of Excellence Department of Internal Medicine Taichung Veterans General Hospital Taichung Taiwan School of Medicine Chung Shan Medical University Taichung 402 Taiwan Ph.D. Program in Translational Medicine National Chung Hsing University Taichung 402 Taiwan Department of Medical Technology Jen-Teh Junior College of Medicine Nursing and Management Miaoli Taiwan. Department. of Electrical Engineering National Tsing Hua University Hsinchu Taiwan. Division of Pulmonary and Critical Care Medicine Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taiwan Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taiwan. Department. of Electrical Engineering National Tsing Hua University Hsinchu Taiwan. Electronic address: kttang@ee.nthu.edu.tw. Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan. Electronic address: jywang@ntu.edu.tw. Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Respiratory Therapy Kaohsiung Medical University Hospital Kaohsiung Taiwan Department of Biological Science & Technology National Chiao Tung University Hsin-Chu Taiwan.

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Evaluation of phase formation and physical-mechanical properties of Portland cements produced with civil construction waste

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CEMENT 2021年 5卷

作者： F.N. Costa D.V. Ribeiro Post-Graduate Program in Civil Engineering (PPEC)/Federal University of Bahia Rua Aristides Novis 02. Federação Salvador BA 40210-630 Brazil Department of Materials Science and Technology Federal University of Bahia Rua Aristides Novis 02. Federação Salvador BA 40210-630 Brazil

Cement is the most widely used building material worldwide. Its production demands a large amount of natural resources, in addition to high energy consumption. Thus, the cement industry has been looking for solutions that effectively reduce the use of these resources as well as greenhouse gas emissions. This research aims to show the technical feasibility of incorporating civil construction waste (CCW) in the production of Portland cement. To this purpose, the physicochemical characterization of the raw materials used was carried out, dosage and manufacture of the raw mix, which were calcined at 1450 °C. Clinkers were characterized mineralogically, by means of XRD, to verify the formation of the crystalline phases. Subsequently, the clinkers were ground, resulting in Portland cements, and their physical-mechanical properties were evaluated. The results showed the potential of using CCW as an alternative raw material, since experimental cements presented performance similar to industrial cements used as a reference.

关键词： Civil construction waste (CCW Reuse Environment Cement Compressive strength

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Freshwater microalgae-mediated engineered nanoparticles: Sustainable approach for heavy metals remediation

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Bioresource technology 2025年 132761页

作者： Manish Sutradhar Raju Kumar Sharma Gobinda Dey Uttara Sukul Koyeli Das Md. Taharia Pin-Yun Lin Shafiqa Ali Chin-Wen Wang Chien-Yen Chen Doctoral Program in Science Technology Environment and Mathematics Department of Earth and Environmental Sciences National Chung Cheng University 168 University Road Min-Hsiung Chiayi County 62102 Taiwan Department of Earth and Environmental Sciences National Chung Cheng University 168 University Road Min-Hsiung Chiayi County 62102 Taiwan Department of Chemistry and Biochemistry National Chung Cheng University 168 University Road Min-Hsiung Chiayi County 62102 Taiwan Center for Nano Bio-Detection Center for Innovative Research on Aging Society AIM-HI National Chung Cheng University 168 University Road Min-Hsiung Chiayi County 62102 Taiwan Department of Biomedical Sciences Graduate Institute of Molecular Biology National Chung Cheng University 168 University Road Min-Hsiung Chiayi County 62102 Taiwan You-Cheng Engineering & Technology Co. Ltd 168 University Road Min-Hsiung Chiayi Country 62102 Taiwan

Recently, convergence of nanotechnology and sustainable approaches has emerged as promising strategy for advanced remediation of heavy metals (HMs) from water. However, engineered nanoparticles (ENPs)-derived from freshwater microalgae gained attention as viable alternative, owing their inherent metal tolerance, rapid-growth rates, and versatile metabolic capabilities. This review predominantly focuses on freshwater microalgae-mediated-ENPs, highlighting intracellular/extracellular pathways induced by biomolecules such as polysaccharides, proteins, lipids, reductases etc., which govern nanoparticle nucleation, stabilization, and functionalization. Subsequently, the review discusses significant types of ENPs including iron, silver, gold, cadmium-sulfide, iron-oxide, nanocomposites, and bio-nano-hybrids nanoparticles, which reported removal efficiency from 21 to 100% of different HMs (lead, cadmium, chromium, copper, zinc, etc.). Despite ENPs exhibit significant potential, their large-scale implementation is constrained by challenges such as scaling-up, nutrient-variability, and high turbidity of wastewater. Future research recommended to focus on optimizing biosynthesis parameters, investigating diverse microalgal-strains, incorporating hybrid nano-materials to enhance their stability, reusability, and scalability for sustainable green-technology.

关键词： Bio-nanotechnology Bioremediation efficiency environmental nano-materials Green synthesis Heavy metal removal Phytoremediation

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Journal of the Formosan Medical Association 2024年第2期123卷 159-178页

作者： Lee, Pei-Lin Wu, Yen-Wen Cheng, Hao-Min Wang, Cheng-Yi Chuang, Li-Pang Lin, Chou-Han Hang, Liang-Wen Yu, Chih-Chieh Hung, Chung-Lieh Liu, Ching-Lung Chou, Kun-Ta Su, Mao-Chang Cheng, Kai-Hung Huang, Chun-Yao Hou, Charles Jia-Yin Chiu, Kuo-Liang Center of Sleep Disorder National Taiwan University Hospital Taipei Taiwan School of Medicine College of Medicine National Taiwan University Taipei Taiwan Division of Cardiology Cardiovascular Medical Center Far Eastern Memorial Hospital New Taipei City Taiwan School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Division of Faculty Development Taipei Veterans General Hospital Taipei Taiwan PhD Program of Interdisciplinary Medicine (PIM) National Yang Ming Chiao Tung University College of Medicine Taipei Taiwan Department of Internal Medicine Cardinal Tien Hospital and School of Medicine College of Medicine Fu Jen Catholic University New Taipei City Taiwan Sleep Center Department of Thoracic Medicine Chang Gung Memorial Hospital Linkou Taiwan School of Medicine Chang Gung University Tauyan Taiwan Division of Respirology Department of Internal Medicine Far Eastern Memorial Hospital New Taipei City Taiwan School of Nursing & Graduate Institute of Nursing China Medical University Taichung Taiwan Sleep Medicine Center China Medical University Hospital Taichung Taiwan Division of Cardiology Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan Cardiovascular Center MacKay Memorial Hospital Taipei Taiwan Institute of Biomedical Sciences Mackay Medical College Taipei Taiwan Division of Chest Departments of Internal Medicine MacKay Memorial Hospital Taipei Taiwan MacKay Medical College New Taipei City Taiwan Division of Clinical Respiratory Physiology Department of Chest Medicine Taipei Veterans General Hospital Taipei Taiwan Sleep Center Division of Pulmonary and Critical Care Medicine Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital Kaohsiung Taiwan Department of Respiratory Care Chang Gung University of Science and Technology Chiayi Taiwan Kao-Ho Hospital Kaohsiung Taiwan Division of Cardiology Department of Internal Medicine E-Da Hospital Kaohsiung Taiwan Division of Cardio

Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients. © 2023 Formosan Medical Association

关键词： Atrial fibrillation Continuous positive airway pressure Heart failure Hypertension Sleep disordered breathing

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Cover Feature: Sodium Ion-Conducting Electrolytes Based on Chloroaluminate Ionic Liquids and δ-NaCl (ChemSusChem 20/2024)

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ChemSusChem 2024年第20期17卷

作者： Sumit Kumar Rajesh Raghupathy Prof. Keti Vezzù Dr. Mounesha N. Garaga Dr. Xiaoping Zhu Prof. Steve Greenbaum Prof. Vito Di Noto Prof. Michele Vittadello Department of Chemistry and Environmental Science Medgar Evers College of the City University of New York (CUNY) 1638 Bedford Avenue Brooklyn NY 11225 USA Bioorganic Research Laboratory Department of Chemistry University of Delhi University Enclave Delhi 110007 India Nano and Bioelectrochemistry Research Laboratory and Carbon Dioxide Research and Green Technology Centre Department of Chemistry School of Advanced Sciences Vellore Institute of Technology Tiruvalam Road Vellore 632014 India Section of Chemistry for the Technology (ChemTech) Department of Industrial Engineering University of Padova Via Marzolo 9 I-35131 Padova PD Italy Department of Physics Hunter College of CUNY 695 Park Avenue New York NY 10021 USA Ph.D. Program in Physics The Graduate Center of CUNY 365 5th Avenue New York New York 10016 USA Centro Studi di Economia e Tecnica dell'Energia Giorgio Levi Cases Via Marzolo 9 I-35131 Padova PD Italy Ph.D. Program in Chemistry The Graduate Center of CUNY 365 5th Avenue New York New York 10016 USA

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Ion-exchanged zeolite as a hybrid system: Fluoxetine removal and antibacterial activity

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Microporous and Mesoporous Materials 2025年 396卷

作者： Gabriela Maria Matos Demiti Natália Cândido Homem Helena Prado Felgueiras Anna Carla Ribeiro Benício Alves de Abreu Filho Mara Heloisa Neves Olsen Scaliante Miguel Torres Rodríguez Rosângela Bergamasco State University of Maringá Department of Chemical Engineering Av. Colombo 5790 Maringá 87020-900 Paraná Brazil Centre for Textile Science and Technology (2C2T) University of Minho (UMinho) Azurém Campus University Street 4800-058 Guimarães Portuguese Republic Simoldes Plastics Research and Innovation Department Comendador António da Silva Rodrigues Street 100 3720-502 Oliveira de Azeméis Portuguese Republic State University of Maringá Department of Biotechnology Genetics and Cell Biology Av. Colombo 5790 Maringá 87020-900 Paraná Brazil State University of Maringá Post-Graduate Program in Food Science Av. Colombo 5790 Maringá 87020-900 Paraná Brazil Metropolitan Autonomous University Division of Basic Science and Engineering Av. San Pablo Xalpa 180 San Martin Xochinahuac Azcapotzalco Ciudad de México 02128 United Mexican States

The increasing consumption of antidepressants, aggravated by the coronavirus disease 2019 (COVID-19) pandemic, has resulted in the detection of compounds such as fluoxetine in drinking water. This substance is highly toxic to aquatic organisms and has the potential for bioaccumulation in aquatic environments. This study evaluated the effects of modifying natural zeolites through ion exchange to enhance their adsorption capacity and assess their multifunctional potential. Natural zeolites were modified by immersion in 0.1 mol L −1 solutions of AgNO 3 , MgCl 2 , FeSO 4 , and FeCl 3 , and their performance in fluoxetine removal was systematically compared. The samples were characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, X-ray fluorescence spectroscopy, thermogravimetric analysis, point of zero charge, scanning electron microscopy, and transmission electron microscopy. Adsorption experiments were conducted with an adsorbent concentration of 1 g L −1 and an initial fluoxetine concentration of 20 mg L −1 . The silver-modified zeolite (ZN-AgNO 3 ), which achieved the best performance among the tested materials, was selected for further testing. The pseudo-second-order and Langmuir models provided the best kinetic and isotherm fits, respectively, with a maximum adsorption capacity of 36.36 mg g −1 , achieved at 308 K and an equilibrium time of 21 h. Desorption experiments showed that the adsorbent maintained recovery rates above 50 % over four cycles of reuse. The main adsorption mechanisms involved ion exchange, electrostatic interactions, and hydrogen bonding, in addition to the affinity of silver with the functional groups of fluoxetine. The adsorbent also inhibited the growth of Escherichia coli . Overall, ZN-AgNO 3 demonstrated potential for fluoxetine removal and antibacterial activity.

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Diallyl trisulfide (DATS) protects cardiac cells against advanced glycation end-product-induced apoptosis by enhancing FoxO3A-dependent upregulation of miRNA-210

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The Journal of nutritional biochemistry 2024年 125卷 109567页

作者： Kuan-Ho Lin Shang-Chuan Ng Shang-Yeh Lu Yueh-Min Lin Shu-Hui Lin Tzu-Cheng Su Chih-Yang Huang Wei-Wen Kuo College of Medicine China Medical University Taichung Taiwan ROC Department of Emergency Medicine China Medical University Hospital Taichung Taiwan ROC. Department of Biological Science and Technology College of Life Sciences China Medical University Taichung Taiwan ROC. Division of Cardiovascular Medicine Department of Internal Medicine China Medical University Hospital Taichung Taiwan ROC. Department of Surgical Pathology Changhua Christian Hospital Changhua Taiwan ROC School of Medicine Chung Shan Medical University Taichung Taiwan ROC Department of Medical Laboratory Science and Biotechnology Central Taiwan University of Science and Technology Taichung Taiwan ROC. Department of Medical Laboratory Science and Biotechnology Central Taiwan University of Science and Technology Taichung Taiwan ROC Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan ROC. School of Medicine Chung Shan Medical University Taichung Taiwan ROC. Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan ROC Center of General Education Buddhist Tzu Chi Medical Foundation Tzu Chi University of Science and Technology Hualien Taiwan ROC Department of Medical Research China Medical University Hospital China Medical University Taichung Taiwan ROC Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan ROC Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan ROC. Department of Biological Science and Technology College of Life Sciences China Medical University Taichung Taiwan ROC Program for Biotechnology Industry China Medical University Taichung Taiwan ROC. Electronic address: wwkuo@mail.cmu.edu.tw.

Diabetic cardiomyopathy is a common complication of diabetes, resulting in cardiac hypertrophy and heart failure associated with excessive reactive oxygen species and mitochondria-mediated apoptosis generation. Mitogen-activated protein kinase-c-Jun N-terminal kinase (MAPK-JNK), regulated by microRNA (miR)-210, affects mitochondrial function and is activated by advanced glycation end-products (AGE) in cardiac cells. Diallyl trisulfide (DATS), an antioxidant in garlic oil, inhibits stress-induced cardiac apoptosis. This study examined whether DATS enhances miR-210 expression to attenuate cardiac apoptosis. We investigated the DATS-mediated attenuation mechanism of AGE-enhanced cardiac apoptosis by modulating miR-210 and its upstream transcriptional regulator, FoxO3a. We found FoxO3a binding sites in the miR-210 promoter region. Our results indicated that DATS treatment inhibited AGE-induced JNK activation, phosphoprotein c-Jun nuclear transactivation, and cardiac apoptosis and reversed the AGE-induced reduction in cardiac miR-210 levels. The luciferase activity after DATS treatment was significantly lower than that of the control and was reversed following AGE treatment. We also showed that FoxO3a, upregulated by DATS treatment, may bind to the miR-210 promoter to enhance its expression and downregulates JNK expression to attenuate AGE-induced cardiac apoptosis. Oral administration of DATS enhanced FoxO3a expression in the heart and reduced diabetes-induced heart apoptosis. Our findings indicate that DATS mediates AGE-induced cardiac cell apoptosis attenuation by promoting FoxO3a nuclear transactivation to enhance miR-210 expression and regulate JNK activation. Our results suggest that DATS can be used as a cardioprotective agent, and miR-210 is a critical regulator in inhibiting diabetic cardiomyopathy.

关键词： Advanced glycation end products (AGEs) Diallyl trisulfide (DATS) Forkhead box O3a (FoxO3a) c-Jun N-terminal kinase (JNK) microRNA-210

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