检索结果-内蒙古大学图书馆

Astrocytic Cebpd Regulates Pentraxin 3 Expression to Promote Fibrotic Scar Formation After Spinal Cord Injury

Molecular neurobiology 2023年第4期60卷 2200-2208页

作者： Shao-Ming Wang Jung-Yu C Hsu Chiung-Yuan Ko Hsiang-En Wu Yu-Wei Hsiao Ju-Ming Wang Graduate Institute of Biomedical Sciences China Medical University Taichung 404333 Taiwan. wangs@mail.cmu.edu.tw. Neuroscience and Brain Disease Center China Medical University Taichung Taiwan. wangs@mail.cmu.edu.tw. Department of Neurology China Medical University Hospital Taichung Taiwan. wangs@mail.cmu.edu.tw. Department of Cell Biology and Anatomy College of Medicine National Cheng Kung University Tainan Taiwan. Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei Taiwan. TMU Research Center of Neuroscience Taipei Medical University Taipei Taiwan. TMU Research Center of Cancer Translational Medicine Taipei Taiwan. Cellular Pathobiology Section Integrative Neuroscience Research Branch Intramural Research Program National Institute on Drug Abuse NIH/DHHS Suite 3512 333 Cassell Drive Baltimore MD 21224 USA. Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan Taiwan. Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan Taiwan. yumingw@mail.ncku.edu.tw. Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan. yumingw@mail.ncku.edu.tw. International Research Center for Wound Repair and Regeneration National Cheng Kung University Tainan Taiwan. yumingw@mail.ncku.edu.tw. Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan. yumingw@mail.ncku.edu.tw. Institute of Bioinformatics and Biosignal Transduction College of Bioscience and Biotechnology National Cheng Kung University Tainan 701 Taiwan. yumingw@mail.ncku.edu.tw.

Astroglial-fibrotic scars resulted from spinal cord injury affect motor and sensory function, leading to paralysis. In particular, the fibrotic scar is a main barrier that disrupts neuronal regeneration after spinal cord injury. However, the association between astrocytes and fibrotic scar formation is not yet understood. We have previously demonstrated that the transcriptional factor Cebpd contributes to astrogliosis, which promotes glial scar formation after spinal cord injury. Herein, we show that fibrotic scar formation was decreased in the epicenter region in Cebpd mice after contusive spinal cord injury and astrocytic Cebpd promoted fibroblast migration through secretion of Ptx3. Furthermore, the expression of Mmp3 was increased under recombinant protein Ptx3 treatment in fibroblasts by observing microarray data, resulting in fibroblast migration. In addition, regulation of Mmp3 occurs through the NFκB signaling pathway by using an irreversible inhibitor of IκBα phosphorylation in pretreated fibroblasts. Of note, we used the synthetic peptide RI37, which blocks fibroblast migration and decreases fibroblast Mmp3 expression in IL-1β-treated astrocyte conditioned media. Collectively, our data suggest that fibroblast migration can be affected by astrocytic Cebpd through the Ptx3/NFκB/Mmp3 axis pathway and that the RI37 peptide may act as a therapeutic medicine to inhibit fibrotic scar formation after spinal cord injury.

关键词： Astrocyte Cebpd Fibrotic scar Ptx3 Spinal cord injury

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data on lung and intestinal microbiome after air pollution exposure in ageing rats

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data in brief 2023年 47卷 109004页

作者： Vincent Laiman Yu-Chun Lo Hsin-Chang Chen Tzu-Hsuen Yuan Ta-Chih Hsiao Jen-Kun Chen Ching-Wen Chang Ting-Chun Lin Ssu-Ju Li You-Yin Chen didik Setyo Heriyanto Kian Fan Chung Kai-Jen Chuang Kin-Fai Ho Jer-Hwa Chang Hsiao-Chi Chuang International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei Taiwan. Department of Anatomical Pathology Faculty of Medicine Public Health and Nursing Universitas Gadjah Mada - Dr. Sardjito Hospital Yogyakarta Indonesia. Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Department of Chemistry College of Science Tunghai University Taichung Taiwan. Department of Health and Welfare College of City Management University of Taipei Taipei Taiwan. Graduate Institute of Environmental Engineering National Taiwan University Taipei Taiwan. Institute of Biomedical Engineering & Nanomedicine National Health Research Institutes Miaoli Taiwan. Industrial Ph.D. Program of Biomedical Science and Engineering National Yang Ming Chiao Tung University Taipei Taiwan. Department of Biomedical Engineering National Yang Ming Chiao Tung University Taipei Taiwan. National Heart and Lung Institute Imperial College London London UK. School of Public Health College of Public Health Taipei Medical University Taipei Taiwan. Department of Public Health School of Medicine College of Medicine Taipei Medical University Taipei Taiwan. School of Public Health and Primary Care the Chinese University of Hong Kong Hong Kong. School of Respiratory Therapy College of Medicine Taipei Medical University 250 Wuxing Street Taipei 11031 Taiwan. Division of Pulmonary Medicine Departments of Internal Medicine Wan Fang Hospital Taipei Medical University Taipei Taiwan. Division of Pulmonary Medicine Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan. Cell Physiology and Molecular Image Research Center Wan Fang Hospital Taipei Medical University Taipei Taiwan. Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan.

Air pollution has been linked to respiratory diseases, and urban air pollution can be attributed to a number of emission sources. The emitted particles and gases are the primary components of air pollution that enter the lungs during respiration. Particulate matter with an aerodynamic diameter of ≤ 2.5 µm (PM) can deposit deep into the respiratory tract via inhalation and has been proposed as a causative agent for adverse respiratory health. In addition, the lung contains a diverse microbial community (microbiome) that maintains normal homeostasis and is significantly altered in a variety of pulmonary disorders. Air pollution, specifically PM, has previously been shown to significantly alter the composition of the lower airway microbiome, which has been linked to decreased lung function in chronic obstructive pulmonary disease (COPd) patients. Surprisingly, the intestinal microbiome has also been implicated in the modulation of pulmonary inflammatory diseases. Therefore, dysbiosis of the lung and intestinal microbiomes pose significant negative effects on human health. This dataset describes the microbial community profiles of the lungs and intestines of ageing rats exposed to ambient unconcentrated traffic-related air pollution for three months. The whole-body exposure system was equipped with and without high efficiency particulate air (HEPA) filtration (gaseous vs. PM pollution). The data can provide valuable information on lung and intestinal microbiome changes, including that which was only found after traffic-related air pollution exposure.

关键词： Air pollution Intestinal microbiome Lung microbiome PM2.5

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Corrigendum to "WNK1 kinase signaling in metastasis and angiogenesis"

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Cellular signalling 2022年 96卷 110377页

作者： Chia-Ying Hou Chung-Yung Ma Chiou-Hwa Yuh Institute of Molecular and Genomic Medicine National Health Research Institutes Miaoli Taiwan Institute of Biotechnology National Tsing Hua University Hsinchu Taiwan. Institute of Molecular and Genomic Medicine National Health Research Institutes Miaoli Taiwan. Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu Taiwan Department of Biological Science and Technology National Chiao Tung University Hsinchu Taiwan Ph.D. Program in Environmental and Occupational Medicine Kaohsiung Medical University Kaohsiung Taiwan. Electronic address: chyuh@nhri.edu.tw.

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Plasma-derived Nanoclusters for Site-Specific Multimodality photo/Magnetic Thrombus Theranostics

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Advanced Healthcare Materials 2023年第28期12卷 e2301504页

作者： Liu, Chia-Hung Liu, Ming-Che Jheng, Pei-Ru Yu, Jiashing Fan, Yu-Jui Liang, Jia-Wei Hsiao, Yu-Cheng Chiang, Chih-Wei Bolouki, Nima Lee, Jyh-Wei Hsieh, Jang-Hsing Mansel, Bradley W Chen, Yan-Ting Nguyen, Hieu Trung Chuang, Er-Yuan Department of Urology School of Medicine College of Medicine Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan TMU Research Center of Urology and Kidney Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan Department of Urology Shuang Ho Hospital Taipei Medical University 291 Zhongzheng Road Zhonghe District New Taipei City23561 Taiwan Clinical Research Center Taipei Medical University Hospital Taipei11031 Taiwan School of Dental Technology College of Oral Medicine Taipei Medical University Taipei11031 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering International Ph.D. Program in Biomedical Engineering Graduate Institute of Biomedical Optomechatronics School of Biomedical Engineering Research Center of Biomedical Device Innovation Entrepreneurship Education Center College of Interdisciplinary Studies Taipei Medical University Taipei11031 Taiwan Department of Chemical Engineering College of Engineering National Taiwan University Taipei106 Taiwan Department of Orthopedics Taipei Medical University Taipei11031 Taiwan Department of Orthopedics Taipei Medical University Hospital Taipei11031 Taiwan Department of Physical Electronics Faculty of Science Masaryk University Brno60177 Czech Republic Department of Materials Engineering Ming Chi University of Technology New Taipei City24301 Taiwan Center for Plasma and Thin Film Technologies Ming Chi University of Technology New Taipei City24301 Taiwan National Synchrotron Radiation Research Center Hsinchu Science Park Hsinchu30076 Taiwan Department of Orthopedics and Trauma Faculty of Medicine University of Medicine and Pharmacy at Ho Chi Minh City Ho Chi Minh City700000 Viet Nam Cell Physiology and Molecular Image Research Center Taipei Medical University Wan Fang Hospital Taipei11696 Taiwan Precision Medicine and Translational Cancer Research Center Taipei Medical University Hospital Taipei11031 Taiwan

Traditional thrombolytic therapeutics for vascular blockage are affected by their limited penetration into thrombi, associated off-target side effects, and low bioavailability, leading to insufficient thrombolytic efficacy. It is hypothesized that these limitations can be overcome by the precisely controlled and targeted delivery of thrombolytic therapeutics. A theranostic platform is developed that is biocompatible, fluorescent, magnetic, and well-characterized, with multiple targeting modes. This multimodal theranostic system can be remotely visualized and magnetically guided toward thrombi, noninvasively irradiated by near-infrared (NIR) phototherapies, and remotely activated by actuated magnets for additional mechanical therapy. Magnetic guidance can also improve the penetration of nanomedicines into thrombi. In a mouse model of thrombosis, the thrombosis residues are reduced by ≈80% and with no risk of side effects or of secondary embolization. This strategy not only enables the progression of thrombolysis but also accelerates the lysis rate, thereby facilitating its prospective use in time-critical thrombolytic treatment. © 2023 Wiley-VCH GmbH.

关键词： diseases

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Theoretical study of intermolecular interactions in protic ionic liquids: a single ion pair picture

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Journal of physics: Conference Series 2021年第1期1719卷

作者： P Nanthanasit N Chattrapiban M Jitvisate P Nimmanpipug S Rimjaem Ph.D. Degree Program in Physics (International Program) Department of Physics and Materials Science Faculty of Science Chiang Mai University Chiang Mai 50200 Thailand Plasma and Beam Physics Research Facility Department of Physics and Materials Science Faculty of Science Chiang Mai University Chiang Mai 50200 Thailand Thailand Center of Excellence in Physics Ministry of Higher Education Science Research and Innovation Bangkok 10400 Thailand The Establishment of Research Center for Quantum Technology Faculty of Science Chiang Mai University Chiang Mai 50200 Thailand Computational Simulation and Modelling Laboratory Faculty of Science and Center of Excellence for Innovation in Analytical Science and Technology Chiang Mai University Chiang Mai 50200 Thailand

Protic ionic liquids are made via intermolecular transfer between cation and anion. This research employs theoretical calculation to gain understanding of the intermolecular interactions at single-ion-pair level and their consequences to the macroscopic properties of the ionic liquids. The protic ionic liquids used in this study are ethylammonium nitrate (EAN), propylammonium nitrate (PAN), and butylammonium nitrate (BAN). Molecular structures of ions and ion pair of each liquid are optimized using the density functional theory. The ion pair binding energies and infrared spectra of optimized structures are investigated. Infrared spectra of separated cation and anion are compared with cation-anion ion pair to specify the vibrational band shifts due to intermolecular interactions. The infrared-spectra show the hydrogen-bond stretching modes in the far-infrared region at the wavenumber between 108-252 cm−1 and the red shifts of four vibrational bands due to intermolecular interactions between the ions. Three vibrational band shifts are mainly due to Coulomb force, and the other shift is caused by combination of intermolecular interactions. Moreover, the energy calculations show that the binding energy decreases as the alkyl chain length increases.

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Self-Awareness for Autonomous Systems

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PROCEEdINGS OF THE IEEE 2020年第7期108卷 971-975页

作者： dutt, Nikil Regazzoni, Carlo S. Rinner, Bernhard Yao, Xin Nikil Dutt (Fellow IEEE) received the Ph.D. degree from the University of Illinois at Urbana–Champaign Champaign IL USA in 1989.""He is currently a Distinguished Professor of computer science (CS) cognitive sciences and electrical engineering and computer sciences (EECS) with the University of California at Irvine Irvine CA USA. He is a coauthor of seven books. His research interests include embedded systems electronic design automation (EDA) computer architecture distributed systems healthcare Internet of Things (IoT) and brain-inspired architectures and computing.""Dr. Dutt is a Fellow of ACM. He was a recipient of the IFIP Silver Core Award. He has received numerous best paper awards. He serves as the Steering Committee Chair of the IEEE/ACM Embedded Systems Week (ESWEEK). He is also on the steering organizing and program committees of several premier EDA and embedded system design conferences and workshops. He has served on the Editorial Boards for the IEEE Transactions on Very Large Scale Integration (VLSI) Systems and the ACM Transactions on Embedded Computing Systems and also previously served as the Editor-in-Chief (EiC) for the ACM Transactions on Design Automation of Electronic Systems. He served on the Advisory Boards of the IEEE Embedded Systems Letters the ACM Special Interest Group on Embedded Systems the ACM Special Interest Group on Design Automationt and the ACM Transactions on Embedded Computing Systems. Carlo S. Regazzoni (Senior Member IEEE) received the M.S. and Ph.D. degrees in electronic and telecommunications engineering from the University of Genoa Genoa Italy in 1987 and 1992 respectively.""He is currently a Full Professor of cognitive telecommunications systems with the Department of Electrical Electronics and Telecommunication Engineering and Naval Architecture (DITEN) University of Genoa and a Co-Ordinator of the Joint Doctorate on Interactive and Cognitive Environments (JDICE) international Ph.D. course started initially as EU Erasmus Mundus Project and

Autonomous systems are able to make decisions and potentially take actions without direct human intervention, which requires some knowledge about the system and its environment as well as goal-oriented reasoning. In computer systems, one can derive such behavior from the concept of a rational agent with autonomy (“control over its own actions”), reactivity (“react to events from the environment”), proactivity (“act on its own initiative”), and sociality (“interact with other agents”) as fundamental properties \n[1]\n. Autonomous systems will undoubtedly pervade into our everyday lives, and we will find them in a variety of domains and applications including robotics, transportation, health care, communications, and entertainment to name a few. \nThe articles in this month’s special issue cover concepts and fundamentals, architectures and techniques, and applications and case studies in the exciting area of self-awareness in autonomous systems.

关键词： Special issues and sections Autonomous systems Self-aware Robot sensing systems Computational modeling

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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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Persistence and dynamic structures of diverse cephalosporinase genes in nontyphoidal Salmonella in cross-sectional surveillance in Taiwan

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international Journal of Antimicrobial Agents 2023年第4期62卷 106944-106944页

作者： Lee, Yuarn-Jang Chang, Yu-Chu Lee, I-Hui Ho, Kuo-Hao Fang, Shiuh-Bin Lauderdale, Tsai-Ling Chen, Ting-Wen Chen, Ku-Chung Huang, Chih-Hung Huang, Tzu-Wen Division of Infectious Diseases Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Division of Infectious Diseases Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Biochemistry and Molecular Cell Biology School of 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 Department of Microbiology and Immunology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan Division of Pediatric Gastroenterology and Hepatology Department of Pediatrics Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Department of Medical Research Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Department of Pediatrics School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Master Program in Clinical Pharmacogenomics and Pharmacoproteomics College of Pharmacy Taipei Medical University Taipei Taiwan National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Zhunan Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu Taiwan Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B) National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Chemical Engineering and Biotechnology Institute of Chemical Engineering National Taipei University of Technology Taipei Taiwan

Objectives: Nontyphoidal Salmonella (NTS) is a major foodborne pathogen causing from acute gastroenteritis to bacteraemia, particularly in paediatric and elderly patients. Antimicrobial resistance of NTS, especially resistance to extended-spectrum cephalosporins, has emerged over the past decades. Methods: Thirteen NTS isolates resistant to ceftriaxone or cefotaxime were collected from a teaching hospital in Taipei, and another three from a tertiary hospital, in New Taipei City, Taiwan, from September 2018 to december 2019. Ten other archived isolates from 2000 to 2017 were also obtained. Complete genomes of the 26 isolates were obtained. Serovars, sequence types, resistomes, genetic relatedness, and sequence comparison of plasmids were analyzed. Results: Serogroups B, C2 and E were significantly associated with ampicillin resistance. Over 90% of these 26 isolates are susceptible to carbapenems and colistin. Genomic epidemiology of these isolates shows that bla_CMY-2-harbouring isolates in different serovars were prevalent over two decades, presumably resulting from highly mobile IncI1 plasmid harbouring bla_CMY-2. One type of the IncI1 plasmids contained a mobile element, IS26, which might be involved in the acquisition of antimicrobial resistance genes. Two emerging serovars, S. Goldcoast ST358 harbouring bla_CTX-M-55 on IncHI2 plasmids and S. Anatum ST64 harbouring bla_dHA-1 on IncA/C₂ plasmids persisted in Taiwan, possibly through the clonal spread. Integration of complete or partial plasmid sequences into host chromosomes or multiplications of the antimicrobial resistance genes also appears to be mediated by IS26, in the two emerging clones. Conclusion: The dynamic movement of cephalosporinase genes mediated by IS26 in NTS is of great concern. © 2023 The Authors

关键词： Amplification Chromosome integration Epidemiology Foodborne pathogen Insertion sequence Whole-genome sequencing

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development and validation of a novel combinational index of liquid biopsy biomarker for longitudinal lung cancer patient management

The journal of liquid biopsy

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The journal of liquid biopsy 2024年 6卷 100167页

作者： Min-Yi Liao Yun-Jie Hao Ching-Shan Luo Ching-Mei Chen Po-Hao Feng Hsin-Yu Yang da-Jeng Yao Kang-Yun Lee Fan-Gang Tseng Department of Power Mechanical Engineering National Tsing Hua University Hsinchu 30013 Taiwan. Department of Engineering and System Science National Tsing Hua University Hsinchu 30013 Taiwan. International Ph.D. Program in Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan. Division of Pulmonary Medicine Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City 23561 Taiwan. TMU Research Center of Thoracic Medicine Taipei Medical University Taipei 11031 Taiwan. Division of Pulmonary Medicine Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan. Nano Science and Technology Program National Tsing Hua University Hsinchu 30013 Taiwan. Institute of Nano Engineering and Micro Systems (NEMS) National Tsing Hua University Hsinchu 30013 Taiwan. Graduate Institute of Clinical Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan. Frontier Research Center on Fundamental and Applied Sciences of Matters National Tsing Hua University Hsinchu 30013 Taiwan.

Objectives:Many cancer biomarkers such as the circulating tumor cells/microemboli (CTCs/CTM) have been reported significant associations with clinical outcomes. However, different biomarkers have different sensitivities and specificities for cancer types and cohort patients, and synergistic effects between certain biomarkers have also been observed, leading to the inaccurate, fluctuating, and even controversial results when multiple biomarkers are analyzed together. In this paper, a novel combinational index, P-score, was developed for monitoring and predicting the disease condition of lung cancer patients during follow-up visits. Materials and methods:There were totally 13 return patients with 54 blood samples involved in this study to examine the number of CTC and CTM. Information from one group of 7 patients including 27 blood samples with published clinical data was employed to develop while those from another group of 4 patients containing 14 blood samples with unpublished clinical data were used to validate the P score in prediction. Enumerations were based on immunofluorescent staining images. distributions of CTC/CTM and their frequencies in stratified patients were carefully examined and analyzed the ROC curve and AUC value to develop the P score and P score-based prediction model. Results and conclusion:We found that the predictive power of P-score was not only comparable to the traditional cancer marker, in comparison with individual CTC/CTM, more false positives could be corrected by using P-score, thereby to improve the accuracy of analysis. From our preliminary validation tests, the prognosis and disease progression monitored longitudinally by P-score were further confirmed by clinical outcome data from physicians and its sensitivity was even better than those from individual biomarkers. We believe that this novel combinational indicator could be a promising tool to interpret clinical outcomes more accurately from multiple factors, particularly useful

关键词： Circulating tumor cells/microemboli Combinational index disease monitoring and prognosis drug screening Lung cancer

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Synthesis of Electrophilic Cyclopent-2-enone Conjugates With Modulatory Effects on Inflammatory Responses Mediated by Nrf2/Keap1, NF-κB and IL-6

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ChemistrySelect 2024年第30期9卷

作者： Gabriel Luis L. Neri Yi-Siao Chen Hans Christian P. Arturo Mark Tristan J. Quimque Warren S. Vidar Young-Sam Keum Chen-Chung Liao Chia-Hung Yen Allan Patrick G. Macabeo Laboratory for Organic Reactivity Discovery and Synthesis (LORDS) Research Center for the Natural and Applied Sciences University of Santo Tomas 1015 España Manila Philippines The Graduate School University of Santo Tomas 1015 España Manila Philippines Ph.D. Program in Environmental and Occupational Medicine College of Medicine Kaohsiung Medical University and National Health Research Institutes Kaohsiung 80708 Taiwan Department of Chemistry College of Science and Mathematics Mindanao State University-Iligan Institute of Technology 9200 Tibanga Iligan City Philippines College of Pharmacy and Integrated Research Institute for Drug Development Dongguk University 32 Dongguk-ro 10326 Goyang Gyeonggi-do Korea Cancer Progression Research Center National Yang Ming Chiao Tung University Taipei 112 Taiwan Graduate Institute of Natural Products College of Pharmacy Kaohsiung Medical University Kaohsiung 80708 Taiwan Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung Taiwan

Cyclopent-2-enone bearing natural products possess anti-inflammatory, cytotoxic, antiproliferative, and antimicrobial activities attributed to the presence of a Michael acceptor enone group acting as a bait for protein targets. To explore the biological activity of synthetic small molecules bearing the cyclopent-2-enone moiety, a collection of 4-substituted cyclopent-2-enones ( 3 a – 3 i ) was prepared synthetically using Lewis acid-catalyzed Mukaiyama-Michael reaction (MMR) in modest to high yields. These derivatives were screened for their effect on inflammatory response mediators, namely Nrf2, NF-κB, and IL-6 through cell-based reporter assays. The results show that 5-(4-oxocyclopent-2-en-1-yl)furan-2(5 H )-one ( 3 g ) is a potent Nrf2 activator in HaCaT cells. The mechanism of Nrf2 activation by 3 g was investigated through an MS/MS-directed proteomic analysis and have shown the formation of a Michael adduct via cysteine-613 on Keap1, an inhibitor of Nrf2. density functional theory calculations show favorable Michael adduct formation between 3 g and the truncated Keap1 tripeptide Pro-Cys613-Ala at the β-carbon of the cyclopent-2-enone moiety. On the other hand, the derivative 4-(2-oxo-2-phenylethyl)cyclopent-2-en-1-one ( 3 a ) exhibited selective Nrf2 inhibition in the cancer cell line Huh7, and inhibitory activity along with 3 g against NF-κB, and IL-6 in RAW 264.7 cells. This points to the cyclopent-2-enone group being an effective scaffold for anti-inflammatory drug designs.

关键词： Cyclopentenones Nrf2 Keap1 Michael acceptor drug discovery

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