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Buparlisib and ponatinib inhibit aggressiveness of cholangiocarcinoma cells via suppression of IRS1-related pathway by targeting oxidative stress resistance

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Biomedicine and Pharmacotherapy 2024年 180卷 117569-117569页

作者： Kaewlert, Waleeporn Sakonsinsiri, Chadamas Lert-itthiporn, Worachart Mahalapbutr, Panupong Ali, Saba Rungrotmongkol, Thanyada Jusakul, Apinya Armartmuntree, Napat Pairojkul, Chawalit Feng, Guofei Ma, Ning Pinlaor, Somchai Murata, Mariko Thanan, Raynoo Department of Biochemistry Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Cholangiocarcinoma Research Institute Khon Kaen University Khon Kaen 40002 Thailand Center of Excellence in Structural and Computational Biology Department of Biochemistry Faculty of Science Chulalongkorn University Bangkok 10330 Thailand Program in Bioinformatics and Computational Biology Graduated School Chulalongkorn University Bangkok 10330 Thailand The Center for Research and Development of Medical Diagnostic Laboratories Faculty of Associated Medical Sciences Khon Kaen University Khon Kaen 40002 Thailand Department of Medical Science Amnatcharoen Campus Mahidol University Amnat Charoen 37000 Thailand Department of Pathology Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Department of Environmental and Molecular Medicine Mie University Graduate School of Medicine Mie 514-8507 Japan Graduate School of Health Science Suzuka University of Medical Science Suzuka Mie 510-0226 Japan Department of Parasitology Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand

Cholangiocarcinoma (CCA) is an oxidative stress-driven liver cancer with bile duct epithelial cell phenotypes and currently lacks effective treatments, making targeted drug therapy urgently needed. Oxidative stress plays a critical role in CCA carcinogenesis, involving cells with oxidative stress resistance via upregulation of the PI3K and MEKK3 signaling pathways. In this study, we investigated the antineoplastic efficacy of a PI3K inhibitor (buparlisib) and a multi-tyrosine kinase inhibitor (ponatinib) on CCA. The cytotoxicity of the drug combination was studied in vitro using CCA cell lines and in vivo using CCA xenograft models. It was found that the drug combination suppressed growth, colony formation, and migration abilities of CCA cells and induced oxidative damage, cell cycle arrest, and autophagy by suppressing MEKK3 and YAP1 through inhibition of insulin receptor substrate 1 (IRS1) signaling. Moreover, the drugs would potentially bind to the IRS1 protein, significanly decreasing IRS1 phosphorylation. Additionally, the drug combination significantly diminished the expression of YAP1, the cell proliferation marker and an antioxidant regulator, and increased oxidative stress-responsive markers in the xenograft model. In conclusion, targeting oxidative stress resistance with combined buparlisib and ponatinib suppressed tumor growth and migration by repressing IRS1-related pathways and ultimately inducing oxidative damage, suggesting the potential for targeted therapy and clinical trials in CCA patients over the use of a single drug. © 2024 The Authors

关键词： Anti-cancer Bile duct cancer Buparlisib Insulin receptor substrate 1 Ponatinib Targeted therapy

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Design and energy assessment of a new hybrid solar drying dome - Enabling Low-Cost, Independent and Smart Solar Dryer for Indonesia Agriculture 4.0

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IOP Conference Series: Earth and Environmental Science 2022年第1期998卷

作者： F E Gunawan A S Budiman B Pardamean E Djuana S Romeli N Hananda C Harito D P B Aji D N N Putri Stevanus Industrial Engineering Department BINUS Graduate Program - Master of Industrial Engineering Bina Nusantara University Jakarta Indonesia 11480 Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta 11480 Indonesia Computer Science Department BINUS Graduate Program - Master of Computer Science Bina Nusantara University Jakarta Indonesia 11480 Electrical Engineering Department Faculty of Industrial Technology Universitas Trisakti Jakarta 11440 Indonesia PT. Impack Pratama Industri Jakarta Indonesia Industrial Engineering Department Faculty of Engineering Bina Nusantara University Jakarta 11480 Indonesia. Mechanical Engineering Department. Faculty of Industrial Technology Universitas Trisakti Jakarta 11440 Indonesia

Solar dryer is typically used for agricultural purposes in Indonesia. There are many economically important crops requiring storage or drying under particular environmental conditions such as temperature and humidity. High temperatures inside solar dryer prevents the growth of microorganism, and quickly reduce moisture content from the substance. A hybrid solar dryer is generally considered to provide the most optimum solution, however solar panels may be expensive and they still only provide heat or energy in the daytime. Hence, we propose here a new kind of hybrid solar dryer for 24/7 optimum conditions for crops - enabled by recent advances in energy technologies as well as Industry 4.0. This study aims to create an efficient, affordable and a self-sufficient intelligent energy system that will be applied to agriculture for storage or drying purposes by measuring the energy needs for the optimal drying system. Therefore, it is crucial to estimate and assess the critical energy needs for such new systems in order to optimize and design such smart solar dryer (SSD) system especially for Indonesia's agricultural needs. We use design experience of our industry partner (PT Impack Pratama Industri, Indonesia) who has been working extensively on such solar dryer dome (SDD) based on polycarbonate material (only solar irradiation, no other technologies) and theoretical framework based on first principles in thermodynamics to estimate and assess critical energy needs for such dome with all the smart technologies. The calculation was performed based on Mollier diagram and the result still a rough estimation of energy required.

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Erratum to: The real cost of sequencing: scaling computation to keep pace with data generation

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Genome biology 2016年第1期17卷 78页

作者： Paul Muir Shantao Li Shaoke Lou Daifeng Wang Daniel J Spakowicz Leonidas Salichos Jing Zhang George M Weinstock Farren Isaacs Joel Rozowsky Mark Gerstein Department of Molecular Cellular and Developmental Biology Yale University New Haven CT 06520 USA. Systems Biology Institute Yale University West Haven CT 06516 USA. Integrated Graduate Program in Physical and Engineering Biology Yale University New Haven CT 06520 USA. Program in Computational Biology and Bioinformatics Yale University New Haven CT 06520 USA. Department of Molecular Biophysics and Biochemistry Yale University New Haven CT 06520 USA. The Jackson Laboratory for Genomic Medicine Farmington CT 06032 USA. Program in Computational Biology and Bioinformatics Yale University New Haven CT 06520 USA. mark@***. Department of Molecular Biophysics and Biochemistry Yale University New Haven CT 06520 USA. mark@***. Department of Computer Science Yale University New Haven CT 06520 USA. mark@***.

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Environmental melamine exposure and adverse kidney outcomes in patients with type 2 diabetes mellitus

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Environmental Pollution 2023年第Part1期331卷 121883页

作者： Tsai, Yi-Chun Wu, Chia-Fang Hung, Wei-Wen Yu, Ping-Shaou Liu, Chia-Chu Hsieh, Tusty-Jiuan Chen, Chu-Chih Li, Sih-Syuan Chen, Jia-Jen Chiu, Yi-Wen Hwang, Shang-Jyh Wu, Ming-Tsang Division of Nephrology Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Division of General Medicine Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Center for Liquid Biopsy and Cohort Research Kaohsiung Medical University Kaohsiung Taiwan School of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan International Master Program of Translational Medicine National United University Miaoli Taiwan Division of Endocrinology and Metabolism Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Kaohsiung Municipal CiJin Hospital Kaohsiung Taiwan Research Center for Precision Environmental Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Urology Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Division of Biostatistics and Bioinformatics Institute of Population Health Sciences National Health Research Institutes Taiwan Department of Public Health College of Health Sciences Kaohsiung Medical University Kaohsiung Taiwan Department of Family Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung City Taiwan Program in Environmental and Occupational Medicine College of Medicine Kaohsiung Medical University Kaohsiung City Taiwan

The impact of melamine exposure on kidney outcomes in type 2 diabetes mellitus (T2D) patients remains unclear. In this prospective cohort study, 561 T2D patients during October 2016 and June 2020 were enrolled and followed until December 2021. Baseline one-spot urinary corrected melamine levels were measured by LC-MS/MS. Average daily intake (ADI) of melamine represented environmental melamine exposure in daily life, and was estimated using urinary corrected melamine level by creatinine excretion (CE)-based model. Primary kidney outcomes were defined as doubling of serum creatinine levels or end stage kidney disease (ESKD), and secondary kidney outcomes included rapid decline in kidney function as estimated glomerular filtration rate (eGFR) decline >5 ml/min/1.73 m2/year. Baseline median urinary corrected melamine levels and estimated DI of melamine were 0.8 μg/mmol and 0.3 μg/kg/day in 561 T2D patients. During 3.7 years of follow-up, urinary corrected melamine level was positively correlated with reaching composite outcomes of either doubling of serum creation levels or ESKD and rapid decline in kidney function. Those with the highest quartile of urinary corrected melamine had 2.96-fold risk of composite outcomes of either doubling of serum creation levels or ESKD and 2.47-fold risk of eGFR decline >5 ml/min/1.73 m2/year. Estimated ADI of melamine also had significant correlation with adverse kidney outcomes. Furthermore, the positive relationship between melamine exposure and rapid decline in kidney function was only found in T2D patients with male, baseline eGFR ≥60 ml/min/1.73 m2 or glycated hemoglobin ≤7%. In conclusion, melamine exposure is significantly associated with adverse kidney outcomes in T2D patients, especially in those with male, well sugar control or good baseline kidney function. © 2023 Elsevier Ltd

关键词： Melamine Kidney outcomes Type 2 diabetes mellitus

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Auf dem Weg zur automatisierten Oligosaccharid‐ Synthese

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Angewandte Chemie 2011年第50期123卷

作者： Che‐Hsiung Hsu Shang‐Cheng Hung Chung‐Yi Wu Chi‐Huey Wong The Genomics Research Center Academia Sinica Taiwan 128 Academia Road Section 2 Nankang Taipei 115 (Taiwan) Chemical Biology and Molecular Biophysics Taiwan International Graduate Program Academia Sinica (Taiwan) Institute of Bioinformatics and Structural Biology National Tsing‐Hua University Hsin‐Chu (Taiwan) Department of Chemistry The Scripps Research Institute 10550 North Torrey Pines Road La Jolla CA 92037 (USA)

Kohlenhydrate spielen eine wichtige Rolle bei biologischen Vorgängen. Das Fortschrittstempo der Kohlenhydratforschung ist jedoch relativ langsam, was unter anderem mit der Komplexität der Kohlenhydratstrukturen und dem Fehlen allgemein anwendbarer Synthesemethoden und Verfahren zur Untersuchung dieser Klasse von Biomolekülen zusammenhängt. Jüngste Fortschritte in der Synthese haben ergeben, dass viele dieser Probleme umgangen werden können. In diesem Aufsatz beschreiben wir die Methoden, die entwickelt wurden, um mit den Herausforderungen kohlenhydratvermittelter biologischer Vorgänge umzugehen. Besonderes Augenmerk wird dabei auf die Entwicklung der automatisierten Synthese von Oligosacchariden gerichtet. Darüber hinaus werden auch Kohlenhydrat‐Mikroarrays und Impfstoffe auf Kohlenhydratbasis behandelt.

关键词： Eintopfreaktionen Festphasensynthese Impfstoffe Kohlenhydrate Mikroarrays

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Comprehensive Functional Characterization of Germline ETV6 Variants Associated with Inherited Predisposition to Acute Lymphoblastic Leukemia in Children

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BLOOD 2016年第22期128卷 1085-1085页

作者： Nishii, Rina Baskin, Rebekah Moriyama, Takaya Hoshitsuki, Keito Metzger, Monika L. Wu, Gang Devidas, Meenakshi Yang, Wenjian Tedrick, Paige Quinn, Emily Gastier-Foster, Julie M. Raetz, Elizabeth Larsen, Eric Martin, Paul L. Bowman, W. Paul Winick, Naomi Takagi, Masatoshi Pui, Ching-Hon Evans, William E. Zhang, Jinghui Relling, Mary V. Hunger, Stephen P. Mullighan, Charles Loh, Mignon L. Nichols, Kim E. Yang, Jun J. Hematological Malignancies Program and Department of Pharmaceutical Sciences St. Jude Children's Research Hospital Memphis TN Department of Pediatrics and Developmental Biology Tokyo Medical and Dental University Graduate School of Medicine Tokyo Japan Department of Oncology St. Jude Children's Research Hospital Memphis TN School of Pharmacy University of Pittsburgh Pittsburgh PA Department of Computational Biology St. Jude Children's Research Hospital Memphis TN Department of Biostatistics College of Medicine Public Health and Health Professions University of Florida Gainesville FL Department of Pathology and Laboratory Medicine Nationwide Children's Hospital Columbus OH Huntsman Cancer Institute University of Utah Salt Lake City UT Maine Children's Cancer Program Scarborough ME Department of Pediatrics Duke University Durham NC Cook Children's Medical Center Fort Worth TX Pediatric Hematology Oncology University of Texas Southwestern Medical Center Dallas TX Oncology St. Jude Children's Research Hospital Memphis TN Department of Computational Biology and Bioinformatics St. Jude Children's Research Hospital Memphis TN

1085

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Homoharringtonine as a PHGDH inhibitor: Unraveling metabolic dependencies and developing a potent therapeutic strategy for high-risk neuroblastoma

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Biomedicine and Pharmacotherapy 2023年第1期166卷 115429-115429页

作者： Hsieh, Chiao-Hui Huang, Chen-Tsung Cheng, Yi-Sheng Hsu, Chun-Hua Hsu, Wen-Ming Chung, Yun-Hsien Liu, Yen-Lin Yang, Tsai-Shan Chien, Chia-Yu Lee, Yu-Hsuan Huang, Hsuan-Cheng Juan, Hsueh-Fen Department of Life Science National Taiwan University Taipei Taiwan Center for Computational and Systems Biology National Taiwan University Taipei Taiwan Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan Institute of Plant Biology National Taiwan University Taipei Taiwan Genome and Systems Biology Degree Program National Taiwan University and Academia Sinica Taipei Taiwan Department of Agricultural Chemistry National Taiwan University Taipei Taiwan Department of Surgery National Taiwan University Hospital and National Taiwan University College of Medicine Taipei Taiwan Department of Pediatrics School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Institute of Biomedical Informatics National Yang Ming Chiao Tung University Taipei Taiwan Center for Advanced Computing and Imaging in Biomedicine Taipei Taiwan

Neuroblastoma, a childhood cancer affecting the sympathetic nervous system, continues to challenge the development of potent treatments due to the limited availability of druggable targets for this aggressive illness. Recent investigations have uncovered that phosphoglycerate dehydrogenase (PHGDH), an essential enzyme for de novo serine synthesis, serves as a non-oncogene dependency in high-risk neuroblastoma. In this study, we show that homoharringtonine (HHT) acts as a PHGDH inhibitor, inducing intricate alterations in cellular metabolism, and thus providing an efficient treatment for neuroblastoma. We have experimentally verified the reliance of neuroblastoma on PHGDH and employed molecular docking, thermodynamic evaluations, and X-ray crystallography techniques to determine the bond interactions between HHT and PHGDH. Administering HHT to treat neuroblastoma resulted in effective cell elimination in vitro and tumor reduction in vivo. Metabolite and functional assessments additionally disclosed that HHT treatment suppressed de novo serine synthesis, initiating intricate metabolic reconfiguration and oxidative stress in neuroblastoma. Collectively, these discoveries highlight the potential of targeting PHGDH using HHT as a potent approach for managing high-risk neuroblastoma. © 2023 The Authors

关键词： Computational molecular docking Drug discovery High-risk neuroblastoma Metabolic reprogramming Molecular target therapy Phosphoglycerate dehydrogenase

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In Reply: Revisiting Claims of the Continued Absence of Functional Germline Stem Cells in Adult Ovaries

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Stem cells (Dayton, Ohio) 2023年第2期41卷 205-206页

作者： Masahito Yoshihara Magdalena Wagner Anastasios Damdimopoulos Cheng Zhao Sophie Petropoulos Shintaro Katayama Juha Kere Fredrik Lanner Pauliina Damdimopoulou Department of Biosciences and Nutrition Karolinska Institutet Stockholm Sweden. Institute for Advanced Academic Research Chiba University Chiba Japan. Department of Artificial Intelligence Medicine Graduate School of Medicine Chiba University Chiba Japan. Division of Obstetrics and Gynecology Department of Clinical Science Intervention and Technology Karolinska Institutet and Karolinska University Hospital Stockholm Sweden. Bioinformatics and Expression Analysis core facility Department of Biosciences and Nutrition Karolinska Institutet Stockholm Sweden. Centre de Recherche du Centre Hospitalier de l'Université de Montréal Axe Immunopathologie H2X 0A9 Montréal Canada. Département de Médecine Université de Montréal Montréal Canada. Folkhälsan Research Center Helsinki Finland. Stem Cells and Metabolism Research Program University of Helsinki Finland. Ming Wai Lau Center for Reparative Medicine Stockholm node Karolinska Institutet Stockholm Sweden.

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Corrigendum to "A Gene Module-Based eQTL Analysis Prioritizing Disease Genes and Pathways in Kidney Cancer"

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Computational and structural biotechnology journal 2018年 16卷 196页

作者： M Q Yang D Li W Yang Y Zhang J Liu W Tong Joint Bioinformatics Graduate Program Department of Information Science George W. Donaghey College of Engineering and Information Technology University of Arkansas at Little Rock USA. University of Arkansas for Medical Sciences 2801 S. University Ave Little Rock AR 72204 USA. School of Computer Science Carnegie Mellon University 5000 Forbes Ave Pittsburgh PA 15213 USA. Department of Statistics Harvard University Cambridge MA 02138 USA. Divisions of Bioinformatics and Biostatistics National Center for Toxicological Research US Food and Drug Administration 3900 NCTR Road Jefferson AR 72079 USA.

[This corrects the article DOI: 10.1016/***.2017.09.003.].

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An integrative and multiscale approach to study dengue virus-like particle dynamics

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Biophysical Journal 2023年第3期122卷 44a-44a页

作者： Venkata Raghuvamsi Palur Gielenny Salem Fan-Chi Chen Shang-Rung Wu Peter J. Bond Day-Yu Chao Jan K. Marzinek Bioinformatics Institute (A∗STAR) Singapore Republic of Singapore Graduate Institute of Microbiology and Public Health College of Veterinary Medicine National Chung Hsing University Taichung City Taiwan Microbial Genomics PhD Program National Chung Hsing University and Academia Sinica Taichung City Taiwan Department of Dentistry & Institute of Oral Medicine National Cheng Kung University Tainan Taiwan Department of Biological Sciences National University of Singapore Singapore Republic of Singapore

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