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Exploration of anti-leukemic effect of soft coral-derived 13-acetoxysarcocrassolide: Induction of apoptosis via oxidative stress as a potent inhibitor of heat shock protein 90 and topoisomerase II

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Kaohsiung Journal of Medical Sciences 2023年第7期39卷 718-731页

作者： Chin, Hsien-Kuo Lu, Mei-Chin Hsu, Kai-Cheng El-Shazly, Mohamed Tsai, Tsen-Ni Lin, Tzu-Yung Shih, Shou-Ping Lin, Tony Eight Wen, Zhi-Hong Yang, Yu-Chen S. H. Liu, Yi-Chang Department of Marine Biotechnology and Resources National Sun Yat-Sen University Kaohsiung Taiwan Division of Cardiovascular Surgery Department of Surgery Kaohsiung Armed Forces General Hospital Kaohsiung Taiwan Graduate Institute of Marine Biology National Dong Hwa University Hualien Taiwan National Museum of Marine Biology and Aquarium Pingtung Taiwan Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan Master Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan Ph.D. Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan TMU Research Center of Drug Discovery Taipei Medical University Taipei Taiwan Department of Pharmacognosy Faculty of Pharmacy Ain-Shams University Cairo Egypt Division of Hematology-Oncology Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taiwan Department and Graduate Institute of Aquaculture National Kaohsiung University of Science and Technology Kaohsiung Taiwan Doctoral Degree Program in Marine Biotechnology National Sun Yat-Sen University Kaohsiung Taiwan Doctoral Degree Program in Marine Biotechnology Academia Sinica Taipei Taiwan Joint Biobank Office of Human Research Taipei Medical University Taipei Taiwan Department of Internal Medicine Faculty of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Cellular Therapy and Research Center Kaohsiung Medical University Hospital Kaohsiung Taiwan

13-Acetoxysarcocrassolide (13-AC) is a marine cembranoid derived from the aquaculture soft coral of Lobophytum crassum. The cytotoxic effect of 13-AC against leukemia cells was previously reported but its mechanism of action is still unexplored. In the current study, we showed that 13-AC induced apoptosis of human acute lymphoblastic leukemia Molt4 cells, as evidenced by the cleavage of PARP and caspases, phosphatidylserine externalization, as well as the disruption of mitochondrial membrane potential. The use of N-acetylcysteine (NAC), a reactive oxygen species (ROS) scavenger, attenuated the cytotoxic effect induced by 13-AC. Molecular docking and thermal shift assay indicated that the cytotoxic mechanism of action of 13-AC involved the inhibition of heat shock protein 90 (Hsp 90) activity by eliciting the level of Hsp 70 and topoisomerase IIα in Molt4 cells. 13-AC also exhibited potent antitumor activity by reducing the tumor volume (48.3%) and weight (72.5%) in the in vivo Molt4 xenograft mice model. Our findings suggested that the marine cembranoid, 13-AC, acted as a dual inhibitor of Hsp 90 and topoisomerase IIα, exerting more potent apoptotic activity via the enhancement of ROS generation. © 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.

关键词： 13-Acetoxysarcocrassolide heat shock protein 90 leukemia oxidative stress topoisomerase II

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2d sheet structure of zinc molybdate decorated on MXene for highly selective and sensitive electrochemical detection of the arsenic drug Roxarsone in water samples

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Chemosphere 2024年 364卷 143188页

作者： Baskaran, Nareshkumar Prasanna, Sanjay Ballur Jeyaram, Kanimozhi Lin, Yu-Chien Govindasamy, Mani Wei, Yang Chung, Ren-Jei Taipei10608 Taiwan Department of Biotechnology Kalasalingam Academy of Research and Education Tamil Nadu Krishnankoil626126 India ZhongSun Co. LTD New Taipei City220031 Taiwan International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan Tamil Nadu Chennai602105 India Research Center for Intelligence Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan Taipei10608 Taiwan

Water contamination is a serious environmental issue posing a significant global challenge. Roxarsone (ROX), a widely used anticoccidial drug is excreted in urine and feces, potentially disrupting natural habitats. Therefore, rapid and cost-effective ROX detection is essential. In this study, we developed a 2d sheet structure of zinc molybdate decorated on MXene (ZnMoO4/MXene) for detecting ROX using electrochemical methods. The materials were characterized using appropriate spectrophotometric and voltammetric techniques. The ZnMoO4/MXene hybrid exhibited excellent electrocatalytic performance due to its rapid electron transfer rate and higher electrical conductivity. The ZnMoO4/MXene-modified GCE (ZnMoO4/MXene/GCE) showed a broad linear range with high sensitivity (10.413 μA μМ−1 cm−2) and appreciable limit of detection (LOd) as low as 0.0081 μM. It also demonstrated significant anti-interference capabilities, excellent storage stability, and remarkable reproducibility. Furthermore, the feasibility of utilizing ZnMoO4/MXene/GCE for monitoring ROX in water samples was confirmed, achieving satisfactory recoveries. © 2024 Elsevier Ltd

关键词： Body fluids

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Self-driven directional polypyrrole-polyethyleneimine nanopigment-infused medical textiles with potential asymmetrical ionic convection and biological effects for follicle restoration

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Journal of Polymer research 2023年第11期30卷 403-403页

作者： Chuang, Sih-Chi Yu, Shih-An Hung, Pei-Chia Chiang, Chih-Wei Su, Wen-Ta Jheng, Pei-Ru Huang, Wei-Yung Hao, Ping-Chien Liang, Jia Wei Lin, Yung-Wei Fang, Hsu-Wei Chuang, Er-Yuan Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei10608 Taiwan Hsuan Chen Technology Co. Ltd. New Taipei22055 Taiwan Bone and Joint Research Center Department of Orthopedics Taipei Medical University Hospital School of Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering Taipei Medical University Taipei11031 Taiwan International Master/Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Taipei Medical University Taipei11031 Taiwan Department of Urology Wan Fang Hospital Taipei Medical University Taipei11696 Taiwan Cell Physiology and Molecular Image Research Center Taipei Medical University-Wan Fang Hospital Taipei11696 Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan

Hair loss is one of the most common and distressing conditions that can be traumatic for an individual. Many non-pharmacological and pharmacological treatments for hair loss have been developed. However, serious side effects or limitations in terms of the hair regeneration potential still exist. One of the non-pharmacological treatments, biophysical stimulation, has shown promise in hair regeneration. Nevertheless, the associated discomfort and the need for external components such as an electrical power supply pose challenges to its widespread use. In this study, we present an innovative cationic fabric that utilizes repeatable asymmetrical ionic flow of a physiological fluid to internally stimulate hair follicles and skin. Characterization, ultrasonic, biochemical, and histological experiments were conducted. The use of this developed treatment significantly increased expressions of heat shock proteins and potentially improved immunoregulation in the skin, as well as increased the number of hair follicles in skin defect animals, with no adverse risks. © 2023, The Polymer Society, Taipei.

关键词： Proteins

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Strategic Procurement and Competitive Advantage

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International Journal of Purchasing and Materials Management 1993年第3期29卷 12-20页

作者： Rajagopal, Shan Bernard, Kenneth N. 1 Shan Rajagopal is a Lecturer in the Department of Marketing at the University of Strathclyde. He received his Ph.D. degree in the development of competitive purchasing strategy from the University of Strathdyde. Dr. Rajagopal's research interests include strategic purchasing global sourcing and relationship management. Prior to joining the academic community he worked for ten years in industry on a world wide basis.2 Kenneth Bernard is a Lecturer in the Department of Marketing at the University of Strathdyde specializing in business-to-business marketing procurement relationship management and technology transfer. Prior to joining the academic community he worked for more than twenty years in marketing management on a world wide basis. He currently is Course Director of the University's MSc in International Marketing Open Learning program.

Since the mid‐1970s there has been a growing, if sporadic, interest in strategic approaches to the procurement process, with an emphasis on the scope for proactivity. However, there has been little consideration of the contribution that may be made to the overall competitive efforts of the organization. This article begins to address this missing link by going back to the fundamental objectives of the purchasing activity and by outlining a framework for the development of a competitive purchasing strategy. The main thrust of such a program centers on the integration of purchasing and procurement operations to satisfy the needs of direct and indirect customers, necessitating constructive management of both inter‐company and intra‐company relationships. The conclusion reached is that purchasing and marketing are not merely interdependent, but that making the “right” procurement decisions is a necessary ingredient in competitive success. Copyright © 1993, Wiley Blackwell. All rights reserved

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SCUBE2 regulates adherens junction dynamics and vascular barrier function during inflammation

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Cardiovascular research 2024年第13期120卷 1636-1649页

作者： Lin, Yuh-Charn Chang, Ya-Jen Gau, Shiang-Shin Lo, Chun-Min Yang, Ruey-Bing Department of Physiology School of Medicine College of Medicine Taipei Medical University Taipei 110301 Taiwan Institute of Biomedical Sciences Academia Sinica 128 Academia Rd. Sec. 2 Taipei 115201 Taiwan Graduate School of Biostudies Kyoto University Kyoto 6068501 Japan Institute for Integrated Cell-Material Sciences (WPI-iCeMS) Kyoto University Kyoto 6068501 Japan Department of Biomedical Engineering National Yang Ming Chiao Tung University Taipei 112304 Taiwan Biomedical Translation Research Center Academia Sinica 99 Ln. 130 Academia Rd. Sec. 1 Taipei 115201 Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University 250 Wuxing St. Taipei 110301 Taiwan

Aims: SCUBE2 (signal peptide-CUB-epidermal growth factor-like domain-containing protein 2) is a secreted or membrane-bound protein originally identified from endothelial cells (ECs). Our previous work showed that SCUBE2 forms a complex with E-cadherin and stabilizes epithelial adherens junctions (AJs) to promote epithelial phenotypes. However, it remains unclear whether SCUBE2 also interacts with vascular endothelial (VE)-cadherin and modulates EC barrier function. In this study, we investigated whether and how SCUBE2 in ECs regulates vascular barrier maintenance. Methods and results: We showed that SCUBE2 colocalized and interacted with VE-cadherin and VE-protein tyrosine phosphatase (VE-PTP) within EC AJs. Furthermore, SCUBE2 knockdown disrupted EC AJs and increased EC permeability. Expression of EC SCUBE2 was suppressed at both mRNA and protein levels via the nuclear factor-κB signalling pathway in response to pro-inflammatory cytokines or permeability-inducing agents. In line with these findings, EC-specific deletion of Scube2 (EC-KO) in mice impaired baseline barrier function and worsened vascular leakiness of peripheral capillaries after local injection of histamine or vascular endothelial growth factor. EC-KO mice were also sensitive to pulmonary vascular hyperpermeability and leucocyte infiltration in response to acute endotoxin- or influenza virus-induced systemic inflammation. Meanwhile, EC-specific SCUBE2-overexpressing mice were protected from these effects. Molecular studies suggested that SCUBE2 acts as a scaffold molecule enabling VE-PTP to dephosphorylate VE-cadherin, which prevents VE-cadherin internalization and stabilizes EC AJs. As such, loss of SCUBE2 resulted in hyperphosphorylation of VE-cadherin at tyrosine 685, which led to its endocytosis, thus destabilizing EC AJs and reducing barrier function. All of these effects were exacerbated by inflammatory insults. Conclusion: We found that SCUBE2 contributes to vascular integrity by recruiting VE-

关键词： Adherens junctions SCUBE2 Vascular permeability VE-cadherin VE-PTP

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Air pollution and its impacts on health: Focus on microplastics and nanoplastics

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Ecotoxicology and environmental safety 2025年 299卷 118402页

作者： Yung-Li Wang Yen-Chung Lin Wen-Chih Liu Yu-Hsuan Lee Hui-Wen Chiu Graduate Institute of Clinical Medicine College of Medicine Taipei Medical University Taipei Taiwan. Division of Nephrology Department of Internal Medicine Taipei Medical University Hospital Taipei Taiwan Division of Nephrology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan TMU Research Center of Urology and Kidney Taipei Medical University Taipei Taiwan. Section of Nephrology Department of Medicine Antai Medical Care Corporation Antai Tian-Sheng Memorial Hospital Pingtung Taiwan Department of Nursing Meiho University Pingtung Taiwan Department of Biology and Anatomy National Defense Medical Center Taipei Taiwan. Department of Cosmeceutics China Medical University Taichung Taiwan Institute of Environmental and Occupational Health Sciences School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan. Electronic address: yhlee@cmu.edu.tw. Graduate Institute of Clinical Medicine College of Medicine Taipei Medical University Taipei Taiwan TMU Research Center of Urology and Kidney Taipei Medical University Taipei Taiwan Department of Medical Research Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Taipei Taiwan. Electronic address: leu3@tmu.edu.tw.

Air pollution represents a significant public health concern, contributing to approximately 6.7 million premature deaths annually. Among the various pollutants, particulate matter (PM), emitted from fossil fuel combustion, poses a significant health risk. It induces oxidative stress and increases respiratory and cardiovascular disease risk. Recently, particulate plastics, classified as microplastics (MPs) (less than 5 mm) or nanoplastics (NPs) (less than 1 μm), have been identified as environmental contaminants. It has been demonstrated that plastic particles, including MPs and NPs, can gain access to the human body via inhalation, ingestion, and dermal contact, resulting in various adverse health effects, such as inflammation and oxidative stress. Particulate plastics have been identified in human biological samples, including blood, saphenous vein tissues and lung tissues. Moreover, their presence in PM, particularly in urban settings, exacerbates the health risks associated with air pollution. This review addresses the sources, detection, health effects, and mitigation strategies for particulate plastics in the atmosphere. Additionally, the study discusses the biological degradation of particulate plastics by microorganisms and the potential of advanced oxidation processes for their removal. These comprehensive approaches could reduce the environment and human health from the adverse effects of airborne particulate plastics.

关键词： Air pollution Health risks Microplastics Nanoplastics Oxidative stress PM(2.5)

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Empirical testing: The prototyper's evaluation mechanism

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NAVAL ENGINEERS JOURNAL 1997年第1期109卷 41-46页

作者： Hafner, AN Arnold N. Hafner Ph.D.:is founder and president of Information Systems Research (ISR). He has twenty-five years of experience in systems development and is published in the field of systems development management. He served as corporate research scientist at Systems Exploration Inc. from 1988 to 1991 program director at Computer Science Corporation from 1983 to 1988 director of operations at Republic Management Systems Corporation from 1981 to 1983 and program manager at Computer Science Corporation from 1972 to 1981. A 1962 graduate of the US. Naval Academy he holds a doctoral degree in human behavior and engineering degrees in electronics and communications. He has taught courses on information systems and systems management at most of the colleges in the San Diego area. Dr. Hafner has presented fourteen refereed research papers while publishing sixteen articles and a book A Manager's Guide to Software System Development.

Evaluating complex systems is the subject of this paper, the third in a series investigating prototyping. It provides an interesting and helpful overview of how to evaluate systems prototypes and outlines the iterative stream of developer-user interactions that is replacing older approaches to testing and evaluating new military systems, which promise to reduce the time required to develop and field future military capabilities. Changes to the acquisition process, such as those the paper sketches, will facilitate the nation's rapid transit through its current revolution in military affairs.

关键词： Systems analysis

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phage display-derived alpaca nanobodies as potential therapeutics for Naja atra snake envenomation

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Applied and Environmental Microbiology 2024年第8期90卷 e0012124页

作者： Wang, Wei-Chu Chang, Jungshan Lee, Chi-Hsin Chiang, Yu-Wei Leu, Sy-Jye Mao, Yan-Chiao Chiang, Jen-Ron Yang, Chun-Kai Wu, Chao-Jung Yang, Yi-Yuan Ph.D. Program in Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taipei Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan International Master/Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei Taiwan International Ph.D. Program for Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei Taiwan School of Medical Laboratory Science and Biotechnology College of Medical Science and Technology Taipei Medical University Taipei Taiwan Core Laboratory of Antibody Generation and Research Taipei Medical University Taipei Taiwan Department of Medical Research Taipei Veterans General Hospital Taipei Taiwan Department of Biology and Anatomy National Defense Medical Center Taipei Taiwan Foundation for Poison Control Taipei Taiwan Department of Microbiology and Immunology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan School of Medicine National Defense Medical Centre Taipei Taiwan Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan Division of Clinical Toxicology Department of Emergency Medicine Taichung Veterans General Hospital Taichung Taiwan Bioproduction Plants National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Miaoli Taiwan Interdisciplinary Research on Ecology and Sustainability National Dong Hwa University Hualien Taiwan

Naja atra, the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated N. atra venom. Following confirmation of the immune response in the alpaca, we amplified VHH genes from isolated peripheral blood mononuclear cells and constructed a phage display VHH library of 1.0 × 107 transformants. After four rounds of biopanning, the enriched phages exhibited increased binding activity to N. atra venom. Four nanobody clones with high binding affinities were selected: aNAH1, aNAH6, aNAH7, and aNAH9. Specificity testing against venom from various snake species, including two Southeast Asian cobra species, revealed nanobodies specific to the genus Naja. An in vivo mouse venom neutralization assay demonstrated that all nanobodies prolonged mouse survival and aNAH6 protected 66.6% of the mice from the lethal dosage. These findings highlight the potential of phage display-derived nanobodies as valuable antidotes for N. atra venom, laying the groundwork for future applications in snakebite treatment. Copyright © 2024 American Society for Microbiology. All Rights Reserved.

关键词： Mammals

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LOCAL INdUSTRIAL development GROUPS: PERSPECTIVES ANd PROFILES

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Review of Policy research 1987年第3期6卷 569-583页

作者： Ottensmeyer, Edward J. Humphrey, Craig R. Erickson, Rodney A. EDWARD OTTENSMEYER (Ph. D. Indiana University) is Assistant Professor of Management at Clark University Worcester Massachusetts. His recent research has focused on strategic issue management systems on strategy development in not-for-profit organizations and on the management of technological innovation. CRAIG HUMPHREY (Ph. D. Brown University) is Associate Professor of Sociology at the Pennsylvania State University University Park Pennsylvania. H i s research has dealt with community development and change. RODNEY ERICKSON (Ph.D. University of Washington) is Professor of Geography and of Business Administration at the Pennsylvania State University University Park Pennsylvania. He also serves as the director of the Pennsylvania Economic Analysis Program at Penn State. His research has focused on theories of regional economic change industrial location and economic development policies.

Local industrial development groups (LIdGs) are often among the most visible organizations involved in community economic development. LIdGs annually spend billions of dollars directly or indirectly in various promotional and community improvement efforts. Yet relatively little is known about their organizational forms, their operating strategies, or their real impact on the economic development of communities. The study reported here was undertaken by researchers from three academic backgrounds in order to capture a rich, comprehensive view of this organizational type. In this paper, we discuss the research perspectives which informed our overall approach to the study, and subsequently, we present and discuss a preliminary profile of LIdGs, based on our recent national survey. Copyright © 1987, Wiley Blackwell. All rights reserved

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Total synthesis and metabolic stability of hispidulin and its d-Labelled derivative

Total synthesis and metabolic stability of hispidulin and it...

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第11届世界华人药物化学研讨会（ISCMC 2018）

作者： Liangchi Chen Kaicheng Hsu Lihchu Chiou Huiju Tseng Weijan Huang Graduate Institute of Pharmacognosy College of PharmacyTaipei Medical University School of Pharmacy College of PharmacyTaipei Medical University Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and TechnologyTaipei Medical University Graduate Institute of Brain and Mind Sciences College of MedicineTaiwan University Graduate Institute of Pharmacology College of MedicineTaiwan University Ph.D.Program in Biotechnology Research and Development College of PharmacyTaipei Medical University Ph.D.Program for the Clinical Drug Discovery from Botanical Herbs College of PharmacyTaipei Medical University School of Pharmacy “Defense Medical Center”

Hispidulin is a naturally occurring flavone known to have various central nervous system(CNS) *** synthetic approaches to synthesizing hispidulin have proven unsatisfactory due to their low feasibility and poor overall *** solve these problems,this study developed a novel scheme for synthesizing hispidulin,which had an improved overall yield as well as more concise reaction steps compared to previous methods ***,using the same synthetic strategy,d-labelled hispidulin was synthesized to investigate its metabolic stability against human liver *** work may produce *** entities for enriching the library of hispidulin-derived compounds.

关键词： hispidulin total synthesis flavone microsome stability deuterium-labelled compound

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