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CXCR7 activation evokes the anti-Pd-L1 antibody against glioblastoma by remodeling CXCL12-mediated immunity

Cell death & disease 2024年第6期15卷 434页

作者： Chan-Chuan Liu Wen-Bin Yang Chia-Hung Chien Cheng-Lin Wu Jian-Ying Chuang Pin-Yuan Chen Jui-Mei Chu Siao Muk Cheng Li-Ying Qiu Yung-Chieh Chang daw-Yang Hwang Chih-Yuan Huang Jung-Shun Lee Kwang-Yu Chang National Institute of Cancer Research National Health Research Institutes Tainan Taiwan. Research Center for Neuroscience Taipei Medical University Taipei Taiwan. Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei Taiwan. School of Medicine I-Shou University Kaohsiung Taiwan. Department of Pathology National Cheng Kung University Hospital College of Medicine National Cheng-Kung University Tainan Taiwan. International Master Program in Medical Neuroscience Taipei Medical University Taipei Taiwan. Department of Biomedical Science and Environmental Biology Kaohsiung Medical University Kaohsiung Taiwan. School of Medicine Chang Gung University Taoyuan Taiwan. Department of Neurosurgery Keelung Chang Gung Memorial Hospital Keelung Taiwan. TMU Research Center of Cancer Translational Medicine Taipei Cancer Center Taipei Medical University Hospital College of Medicine Taipei Medical University Taipei Taiwan. Division of Neurosurgery Department of Surgery National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan. National Institute of Cancer Research National Health Research Institutes Tainan Taiwan. kwang2@nhri.edu.tw. Department of Oncology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan. kwang2@nhri.edu.tw. Center of Cell Therapy National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan. kwang2@nhri.edu.tw.

The interaction between glioblastoma cells and glioblastoma-associated macrophages (GAMs) influences the immunosuppressive tumor microenvironment, leading to ineffective immunotherapies. We hypothesized that disrupting the communication between tumors and macrophages would enhance the efficacy of immunotherapies. Transcriptomic analysis of recurrent glioblastoma specimens indicated an enhanced neuroinflammatory pathway, with CXCL12 emerging as the top-ranked gene in secretory molecules. Single-cell transcriptome profiling of naïve glioblastoma specimens revealed CXCL12 expression in tumor and myeloid clusters. An analysis of public glioblastoma datasets has confirmed the association of CXCL12 with disease and Pd-L1 expression. In vitro studies have demonstrated that exogenous CXCL12 induces pro-tumorigenic characteristics in macrophage-like cells and upregulated Pd-L1 expression through NF-κB signaling. We identified CXCR7, an atypical receptor for CXCL12 predominantly present in tumor cells, as a negative regulator of CXCL12 expression by interfering with extracellular signal-regulated kinase activation. CXCR7 knockdown in a glioblastoma mouse model resulted in worse survival outcomes, increased Pd-L1 expression in GAMs, and reduced Cd8 T-cell infiltration compared with the control group. Ex vivo T-cell experiments demonstrated enhanced cytotoxicity against tumor cells with a selective CXCR7 agonist, VUF11207, reversing GAM-induced immunosuppression in a glioblastoma cell-macrophage-T-cell co-culture system. Notably, VUF11207 prolonged survival and potentiated the anti-tumor effect of the anti-Pd-L1 antibody in glioblastoma-bearing mice. This effect was mitigated by an anti-Cd8β antibody, indicating the synergistic effect of VUF11207. In conclusion, CXCL12 conferred immunosuppression mediated by pro-tumorigenic and Pd-L1-expressing GAMs in glioblastoma. Targeted activation of glioblastoma-derived CXCR7 inhibits CXCL12, thereby eliciting anti-tumor immunity and enha

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Multi-objective design of synthetic biological circuits

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IFAC-PapersOnLine 2017年第1期50卷 9871-9876页

作者： Lormeau C. Rybiński M. Stelling J. Department of Biosystems Science and Engineering ETH Zurich SIB Swiss Institute of Bioinformatics Life Science Zurich Ph.D. program ”Systems Biology” Basel 4058 Switzerland Department of Biosystems Science and Engineering ETH Zurich SIB Swiss Institute of Bioinformatics Basel 4058 Switzerland

Computational methods enable the design of synthetic biological circuits demonstrating a specific dynamic behavior. Current methods are based on the assembly of parts characterized in different contexts, which often fail to operate as predicted when combined. Here we introduce a circuit design method that compensates for parts uncertainty by identifying circuit topologies whose behavior is robust to variations in parameters. Our heuristic topological filtering approach efficiently yields robust circuit designs in a Bayesian framework, and enables to reliably assess trade-offs between performance, robustness, and experimental feasibility, thus increasing the probability of success of circuit implementation. © 2017

关键词： Biocybernetics computer-aided circuit design Multiobjective optimisations Robustness Synthetic biology

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Motion Blitz: a new card game for assessing students' thinking level about physics

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Journal of physics: Conference Series 2019年第1期1380卷

作者： T Thunyaniti S Wuttiprom Ph.D. candidate in Science Education Program Faculty of Science Ubon Ratchathani University Ubon Ratchathani 34190 Thailand Department of Physics Faculty of Science Ubon Ratchathani University Ubon Ratchathani 34190 Thailand Thailand Center of Excellence in Physics CHE Bangkok 10400 Thailand

Critical thinking and problem-solving skills are crucial for the 21st century. Game-based learning (GBL) is a powerful teaching strategy for fostering these skills amongst students. GBL can reinforce knowledge and bridge the gap between what is learned by creating dynamic, fun, and exciting learning environments. This research developed a card game called 'Motion Blitz' for teaching the physics concept of motion in one and two dimensions. Motion Blitz is a quick matching card game that consists of a deck of 'Motion Cards' which picture motions in daily life and a selection of 'Motion Symbols' displaying a path of motions: linear, projectile, circular, rotational, rolling, and simple harmonic motions. To play the game, one player starts by flipping over one of the 'Motion Cards', then simultaneously everyone tries to figure out the proper 'Motion Symbol' to grab. Figure it out and grab the right one to get the card/point. After playing, the teacher uses questions to stimulate student thinking and help students construct scientific knowledge. Finally, 12 questions according to Bloom's taxonomy are administrated to students. These questions are classified according to different cognitive levels ranging from low-level thinking (knowledge, comprehension) to high-level thinking (application, analysis, synthesis, and evaluation). data analyses showed Motion Blitz's ability to elevate students' thinking level, over 90% of students scored well at a low level and 59% at a high level approximately. In addition, data indicated that students' thinking scores became lower at a higher level of thinking.

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SIAN: software for structural identifiability analysis of OdE models

arXiv

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arXiv 2018年

作者： Hong, Hoon Ovchinnikov, Alexey Pogudin, Gleb Yap, Chee Department of Mathematics North Carolina State University Raleigh United States Department of Mathematics CUNY Queens College Ph.D. Programs in Mathematics and Computer Science CUNY Graudate Center New York United States Courant Institute of Mathematical Sciences New York University

Biological processes are often modeled by ordinary differential equations with unknown parameters. The unknown parameters are usually estimated from experimental data. In some cases, due to the structure of the model, this estimation problem does not have a unique solution even in the case of continuous noise-free data. It is therefore desirable to check the uniqueness a priori before carrying out actual experiment. We present a new software SIAN (Structural Identifiability ANalyser) that does this. Our software can tackle problems that could not be tackled by previously developed packages. Copyright © 2018, The Authors. All rights reserved.

关键词： Ordinary differential equations

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Corrigendum to "L-selectin activation regulates Rho GTPase activity via Ca+2 influx in Sertoli cell line, ASC-17d cells"

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Biochemical and biophysical research communications 2021年 584卷 116页

作者： Ivan Limanjaya Tsung-I Hsu Jian-Ying Chuang Tzu-Jen Kao International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei Taiwan. Graduate Institute of Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan College of Medical Science and Technology Taipei Medical University and National Health Research Institutes Taipei Taiwan Research Center of Neuroscience Taipei Medical University Taipei Taiwan TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei Taiwan. TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei Taiwan. Electronic address: chuangcy@tmu.edu.tw. Research Center of Neuroscience Taipei Medical University Taipei Taiwan. Electronic address: geokao@tmu.edu.tw.

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Proton Radiation Studies on Conjugated Polymer Thin Films

Proton Radiation Studies on Conjugated Polymer Thin Films

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MRS Advances

作者： Lee, Harold O. Hasib, Muhammed Sun, Sam-Shajing Center for Materials Research Ph.D. Program in Materials Science and Engineering Norfolk State University NorfolkVA23504 United States Department of Chemistry Norfolk State University NorfolkVA23504 United States

Polymeric thin film based electronic and optoelectronic materials and devices are attractive for potential space and certain radiation related applications due to their inherent features such as being light weight, flexible, biocompatible and environmental friendly, etc. Proton radiation is a major form of ionizing radiation in space, yet very few literature and data are available on proton radiation effects on conjugated polymer systems. In this study, UV-Vis absorption spectra of several conjugated polymers and/or their composite thin films were measured and compared right before and after a 200 MeV proton beam irradiation at different dosages, and the results revealed that proton radiation has very little or negligible impact up to 800 Rads on the optoelectronic properties of several polymers and their composite thin films. Copyright © Materials Research Society 2017.

关键词： Conjugated polymers

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RAB14 activates MAPK signaling to promote bladder tumorigenesis (vol 40, bgz039, 2019)

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CARCINOGENESIS 2019年第9期40卷 1177-1177页

作者： Chao, Haichao deng, Leihong Xu, Fanghua Fu, Bin Zhu, Zunwei dong, Zhifeng Liu, Yen-Nien Zeng, Tao Institute of Clinical Medicine Jiangxi Provincial People’s Hospital Affiliated to Nanchang University Nanchang P.R. China Medical Department of Graduate School Nanchang University Nanchang P.R. China Pathology Department Jiangxi Provincial People’s Hospital Affiliated to Nanchang University Nanchang P.R. China Department of Urology The First Affiliated Hospital of Nanchang University Nanchang P.R. China Department of Urology Jiangxi Provincial People’s Hospital Affiliated to Nanchang University Nanchang P.R. China Medical Department of Graduate School Nanchang University Nanchang P.R. China Graduate Institute of Cancer 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 To whom correspondence should be addressed. Tel: +886-2-2697-2035 ext 113. Fax: +886-2-26558562. Email: liuy@tmu.edu.tw Department of Urology Jiangxi Provincial People’s Hospital Affiliated to Nanchang University Nanchang P.R. China Correspondence may also be addressed to Tao Zeng. Tel: +861-791-86896225. Fax: +861-791-86895863. Email: taozeng40709@***

Bladder cancer (BC) is a fatal invasive malignancy accounting for approximately 5% of all cancer deaths in humans; however, the underlying molecular mechanisms and potential targeted therapeutics for BC patients remain unclear. We report herein that RAB14 was overexpressed in BC tissues and cells with high metastatic potential and its abundance was significantly associated with lymph node metastasis (P = 0.001), a high-grade tumor stage (P = 0.009), poor differentiation (P < 0.001) and unfavorable prognoses of BC patients (P = 0.003, log-rank test). Interference by RAB14 mediated a reduction in the TWIST1 protein and inhibited cell migration and invasion (P < 0.05). Moreover, silencing RAB14 reduced cell proliferation and induced apoptosis in vitro and suppressed tumorigenesis in a mouse xenograft model. We demonstrated that RAB14-promoted BC cancer development and progression were associated with activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase signaling through upregulation of MAPK1/MAPK8 and downregulation of dual-specificity protein phosphatase 6/Src homology 2 domain containing transforming protein/Fos proto-oncogene, AP-1 transcription factor subunit (FOS). We provide evidence that RAB14 acts as a tumor promoter and modulates the invasion and metastatic potential of BC cells via activating the MAPK pathway.

关键词： apoptosis second heart sound s2 signal transduction cell proliferation bladder cancer cancer cell motility down-regulation mitogen-activated protein kinases mitogen activated protein kinase 1 phosphotransferases transplantation heterologous up-regulation (physiology) bladder mice neoplasms transcription factor tumorigenesis twist-related protein 1

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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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Investigation on current transformers for measuring of electron beam pulse current

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Journal of physics: Conference Series 2019年第1期1380卷

作者： P Nanthanasit S Rimjaem Plasma and Beam Physics Research Facility Department of Physics and Materials Science Faculty of Science Chiang Mai University Chiang Mai 50200 Thailand Ph.D. Program in Physics (International Program) Department of Physics and Materials Science Faculty of Science Chiang Mai University Chiang Mai 50200 Thailand Thailand Center of Excellence in Physics Commission on Higher Education Bangkok 10400 Thailand

The radio-frequency (RF) linear accelerator (linac) system of the PBP-CMU Electron Linac Laboratory at the Plasma and Beam physics Research Facility is used as an injector system for future mid-infrared and terahertz free-electron lasers. The properties of electron beams produced from the linac must be controlled appropriately to produce high-quality radiation. One of the most important properties is the electron pulse current that can be measured using a current transformer. A copper wire with proper insulator is wounded around the ferrite-core forming a secondary coil of the current transformer. The electron beam passing through the transformer acts as the current in the primary coil and it induces an electromotive force in the secondary coil. Therefore, the output signal from the secondary coil can be measured and analyzed to be a pulse current of electron beam. The measured current pulse shape and value strongly depend on the characteristics of the current transformer. This study focuses on testing and calibrating of existing current transformers installed in the linac system. In the experiments, the pulse generator was used to generate the input pulse current with various pulse lengths. The output pulses were then sampled with a digital oscilloscope. The experimental results showed that the output pulses from the current transformers have distort shape compared with the input pulses. Consequently, the correction was conducted to provide more accuracy of the measuring value of the electron pulse current. The results of this research can be used as a valuable database for the existing current transformers and to develop the new ones that can provide more accurate results.

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Briavioid d, a rare 7β,8β-epoxybriarane from Briareum violaceum

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Tetrahedron Letters 2023年 118卷

作者： Thanh Hao Huynh Chou-Yuan Ko Hsin-Tzu Liu Yen-Po Chen Mingzi M. Zhang Lun Kelvin Tsou Zhi-Hong Wen Su-Ying Chien Ping-Jyun Sung Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung 804201 Taiwan National Museum of Marine Biology and Aquarium Pingtung 944401 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine Kaohsiung Armed Forces General Hospital Kaohsiung 802301 Taiwan Institute of Medical Science and Technology National Sun Yat-sen University Kaohsiung 804201 Taiwan Department of Medical Research Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien 970473 Taiwan Department of Obstetrics and Gynecology Kaohsiung Armed Forces General Hospital Kaohsiung 802301 Taiwan Institute of Molecular and Genomic Medicine National Health Research Institutes Zhunan Miaoli 350401 Taiwan Institute of Biotechnology and Pharmaceutical Research National Health Research Institutes Zhunan Miaoli 350401 Taiwan Institute of BioPharmaceutical Sciences National Sun Yat-sen University Kaohsiung 804201 Taiwan Instrumentation Center National Taiwan University Taipei 106319 Taiwan Chinese Medicine Research and Development Center China Medical University Hospital Taichung 404394 Taiwan Graduate Institute of Natural Products Kaohsiung Medical University Kaohsiung 807378 Taiwan Ph.D. Program in Pharmaceutical Biotechnology Fu Jen Catholic University New Taipei City 242062 Taiwan

A rare 7β,8β-epoxybriarane, briavioid d ( 1 ), has been isolated from a cultured octocoral Briareum violaceum . The structure of 1 was deduced by extensive 2d NMR studies. Single-crystal X-ray diffraction analysis was performed to identify the structure of 1 and this compound was found to reduce the release of iNOS to 85.77 %, at a concentration of 10 μM.

关键词： Briareum violaceum Briavioid Briarane X-ray iNOS

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