检索结果-内蒙古大学图书馆

Mitochondrial activation via calcium peroxide/carrageenan/soybean lecithin-derived polypyrrole phototherapeutic microparticles

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Colloids and Surfaces B: Biointerfaces 2025年 254卷 114787页

作者： Chuang, Sih-Chi Yu, Shih-An Hung, Pei-Chia Chuang, Andrew E.-Y. Liang, Jia-Wei Sun, Chia-Lu Rethi, Lekshmi Fang, Hsu-Wei Nguyen, Hieu Trung Tsai, Yao-Tung Weng, Pei-Wei Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei10608 Taiwan Doctoral Program of Biochemical and Biomedical Engineering National Taipei University of Technology Taipei10608 Taiwan Taipei Medical University Derived Company-Hsuan Chen Technology CO. LTD. New Taipei City22055 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University New Taipei City Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University New Taipei City Taiwan Cell Physiology and Molecular Image Research Center Taipei Medical University-Wan Fang Hospital Taipei11696 Taiwan WELLCARE Health Care Supply Co. Ltd. Taipei 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 Department of Orthopaedic Surgery Tri-Service General Hospital National Defense Medical Center No. 325 Sec. 2 Chenggong Rd. Neihu Dist. Taipei City11490 Taiwan Division of Traumatology Department of Surgery Tri-Service General Hospital National Defense Medical Center No. 325 Sec. 2 Chenggong Rd. Neihu Dist. Taipei City11490 Taiwan Department of Orthopedics School of Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Department of Orthopedics Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan

Mitochondria, often referred to as the "powerhouses" of eukaryotic cells, play a critical role in maintaining cellular homeostasis and supporting essential life functions, particularly in cell survival and apoptosis. This study introduces a composite formulation—combining carrageenan (Car), calcium peroxide (CaO2), and microparticles, derived from soybean oil lecithin, enhanced with photothermally active polypyrrole (PPy)—to create Car-Lec-PPy MP, aimed at promoting mitochondrial activation in cells. The investigation focuses on intercellular mitochondrial transfer and activation as a therapeutic strategy. The formulation seeks to stimulate mitochondrial biogenesis and enhance cellular resilience through targeted mitochondrial activation, leveraging the synergistic effects of near-infrared (NIR) therapy. In the in vivo experiment, phototherapeutic Car-Lec-PPy MP was administered to rodent muscle tissue. The results showed increased expression of heat-shock proteins and reduced oxidative stress in the treated muscle. Preliminary findings suggest that this approach not only boosts mitochondrial activity but also improves cell proliferation and survival, presenting significant potential for applications in regenerative medicine and cellular therapy. © 2025 Elsevier B.V.

关键词： Mitochondria

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Ultrafast circuit protection for unmanned systems

Ultrafast circuit protection for unmanned systems

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2019 International Conference on Communications, Information System, and Computer engineering, CISCE 2019

作者： Kao, Chih-Hong Huang, Sy-Ruen He, Bo-Rong Lin, Hsiung-Cheng School of Computer Science Minnan Normal University Lab of Granular Computing ZhangZhou Fujjan China Department of Electrical Engineering Feng Chia University Taichung Taiwan Ph.D. Program of Electrical and Communications Engineering Feng Chia University Taichung Taiwan Department of Electrical Engineering Chin-Yi University of Technology Taichung Taiwan

ISBN: (纸本)9781728136813

With increasing dependence on precision electronic equipment, self-protection is becoming essential. The protection circuits commonly used before were fuses and circuit breakers which, however, they are not enough for the current need of high-speed protection circuits and automated engineering logic. In this paper, we develop a new ultrahigh-speed protection circuit, which is over exceeded 20 times faster than traditional circuits and has the ability to self-recover when any failure occurs. With the new circuit developed, it is not necessary to do manual restart and will meet the future needs of protection for electronic precision equipment. This design provides greater convenience and reliability for the unmanned equipment for the future. © 2019 IEEE.

关键词： Timing circuits

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Therapeutic targeting of hepatocellular carcinoma cells with antrocinol, a novel, dual-specificity, small-molecule inhibitor of the KRAS and ERK oncogenic signaling pathways

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Chemico-Biological Interactions 2023年第1期370卷 110329页

作者： Hsu, Chia-Hung Weng, Pei-Wei Chen, Ming-Yao Yeh, Chi-Tai Setiawan, Syahru Agung Yadav, Vijesh Kumar Wu, Alexander T.H. Tzeng, david T.W. Gong, Jian-Xian Yang, Zhen Tzeng, Yew-Min Department of Emergency Medicine Shuang Ho Hospital Taipei Medical University New Taipei City 23561 Taiwan Graduate Institute of Injury Prevention and Control College of Public Health Taipei Medical University Taipei City 11031 Taiwan Department of Emergency Medicine School of Medicine Taipei Medical University Taipei 11031 Taiwan Department of Orthopaedics School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Department of Orthopaedics Shuang Ho Hospital Taipei Medical University New Taipei City 23561 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine Shuang Ho Hospital New Taipei City 23561 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Continuing Education Program of Food Biotechnology Applications College of Science and Engineering National Taitung University Taitung 95092 Taiwan International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Ph.D. Program of Translational Medicine College of Medical Science and Technology Taipei Medical University Taipei 11031 Taiwan School of Life Sciences The Chinese University of Hong Kong 999077 Hong Kong Lifebit London EC2A 2AP United Kingdom Laboratory of Chemical Genomics School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School Shenzhen 518055 China State Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education and Beijing National Laboratory for Molecular Science College of Chemistry and Molecular Engineering Peking University Beijing 100871 China Shenzhen Bay Laboratory Shenzhen 518055 China Department of Applied Science National Taitung University Taitung

Until recently, sorafenib has been the only treatment approved by the U.S. Food and drug Administration for patients with advanced hepatocellular carcinoma (HCC). Some patients, however, exhibit resistance to this treatment and subsequently experience cancer progression, recurrence, or death. Therefore, identifying a new alternative treatment for patients with little or no response to sorafenib treatment is vital. In this study, we explored the therapeutic potential and underlying molecular mechanism of antrocinol ((3aS,4R,6aS,10aR)-4-(hydroxymethyl)-7,7-dimethyldecahydro-1H-naphtho[1,8a-c]furan-1-one) in patients with HCC. The results indicated that antrocinol was more therapeutically effective than antrocin, Stivarga, and sorafenib against HCC cell lines. Antrocinol also substantially suppressed the expression of KRAS-GTP, p-MEK1/2, p-ERK1/2, and p-AKT in the Huh7 cell line. Additionally, antrocinol-induced apoptosis in the Huh7 cell line, inhibited the formation of tumorspheres, and suppressed the expression of cancer stem cell markers Cd133, KLF4, Cd44, OCT4, SOX2, and c-Myc. Animal studies revealed that antrocinol alone considerably suppressed tumor growth in nonobese diabetic/severe combined immunodeficient mice inoculated with Huh7 tumorspheres. It also synergistically enhanced the anticancer effect of sorafenib, resulting in enhanced suppression of tumor growth (p < 0.001) and tumorsphere formation (p < 0.001). In tumor samples resected from mice treated with antrocinol alone or in combination with sorafenib, immunohistochemical analysis revealed an increase in BAX expression and a decrease in ERK and AKT protein expression. To the best of our knowledge, this is the first report of the anti-HCC activity of antrocinol. With its higher therapeutic efficacy than that of sorafenib, antrocinol is a candidate drug for patients with HCC who demonstrate little or no response to sorafenib treatment. © 2022 Elsevier B.V.

关键词： Antrocinol Cancer stemness Hepatocellular carcinoma KRAS/AKT/ERK axis Sorafenib

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Environmental determinants of household microbial and allergen levels in the Greater Taipei Area

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Building and Environment 2023年 230卷

作者： phiri, Yohane V.A. Wu, Meei-Maan Chen, Yi-Hua Zou, Ming-Lun Jiang, Chuen-Bin Wu, Chih-da Huang, Hsiao-Chun Lung, Shih-Chun Candice Chien, Ling-Chu Lo, Yu-Chun Lee, Fang-Yu Chao, Hsing Jasmine 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 Neuroscience Research Center Taipei Medical University Taipei Taiwan Department of Pediatric Gastroenterology Hepatology and Nutrition MacKay Children's Hospital Taipei Taiwan Department of Medicine MacKay Medical College New Taipei City Taiwan Department of Geomatics National Cheng Kung University Tainan Taiwan National Institute of Environmental Health Sciences National Health Research Institute Miaoli Taiwan Research Center for Environmental Changes Academia Sinica Taipei Taiwan Ph.D. Program for Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan

People spend most of their time indoors, where they may be exposed to various microorganisms and allergens. In this cross-sectional study, we investigated the relationship between indoor microbial and allergen levels and indoor and outdoor household environmental characteristics. Participants were recruited from an ongoing cohort study in the Greater Taipei Area. Questionnaire administration and environmental sampling were conducted during home visits. Samples were collected from children's bedrooms, living rooms, kitchens, and outdoor areas (balconies) and analyzed for fungal spores, house dust mite allergens (der p 1 and der f 1), endotoxin, and cockroach allergens (Bla g 1). Indoor temperature and relative humidity were also measured, and the land-use characteristics and points of interest surrounding the residences were evaluated within specified radii. The mean levels of outdoor air pollutants were then estimated, and multiple regression analysis was performed to investigate the predictors of indoor microbial and allergen levels. In total, 136 homes were analyzed. The results indicated that dog ownership, air purifier use, and floor cleaning frequency were major predictors of indoor microbial and allergen levels. Moreover, proximity to parks, roads, and forests was associated with elevated levels of indoor microorganisms and allergens. Our results demonstrated that indoor concentrations of certain microorganisms and allergens tended to increase in households located within neighborhoods with particular characteristics. Overall, our research findings contribute to housing intervention protocols and policies aimed at reducing exposure to indoor microorganisms and allergens. Future studies should longitudinally investigate the health effects of indoor microorganisms and allergens. © 2023 Elsevier Ltd

关键词： Forestry

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Liquefaction Hazard Mapping and Risk Evaluation for Municipal Assets

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KSCE Journal of Civil engineering 2025年

作者： Chih-Wei Lu Yu-Feng Lin Li-Ya Huang Hsiu-Chen Wen Shih-Hao Cheng Kun-Yan Lu Fu-Hsuan Yeh Yu-Syuan Jhuo I-Ping Huang Professor Dept. of Civil and Construction Engineering National Taiwan University of Science and Technology Taipei 10607 Taiwan Ph.D. Student Dept. of Civil and Construction Engineering National Taiwan University of Science and Technology Taipei 10607 Taiwan Former Student Dept. of Civil and Construction Engineering National Taiwan University of Science and Technology Taipei 10607 Taiwan Postdoctoral Researcher Dept. of Civil and Construction Engineering National Taiwan University of Science and Technology Taipei 10607 Taiwan Assistant Professor Taiwan Building Technology Center National Taiwan University of Science and Technology Taipei 10607 Taiwan Former Graduate Student Dept. of Civil and Construction Engineering National Taiwan University of Science and Technology Taipei 10607 Taiwan Assistant Professor Dept. of Civil and Construction Engineering National Taiwan University of Science and Technology Taipei 10607 Taiwan Postdoctoral Researcher Dept. of Civil Engineering National Taiwan University Taipei 10617 Taiwan Commissioner Public Works Department Taipei City Government Taipei 110204 Taiwan

A liquefaction hazard map has been frequently used to assess the risk of building tilt and settlement, pipeline damage, and other conditions. Minimizing the failure of municipal utilities and assets is the key to establishing a resilient city. This study integrates various methods to evaluate the potential risks of municipal assets caused by soil liquefaction. The focus includes liquefaction hazard assessment and maps, building tilt and settlement, road subsidence, pipeline damage, uplift of manholes, and risk assessment. A hazard level was determined using the liquefaction potential index and groundwater level measurements. Considering the degree of impact on rescue operations when a disaster occurs, vulnerability levels were evaluated and graded on buildings, roads, pipelines, and manholes. The vulnerability and hazard levels were combined using a risk matrix to determine the overall risk level. This study demonstrates the risk level of public infrastructure being damaged by soil liquefaction, including buildings, roads, pipelines, and manholes within the region of two emergency routes in Taipei, using the GIS system. The risk assessment map can explain the risk level of municipal assets that affect rescue response in a disaster. This information can be used for future disaster mitigation, prevention, and urban planning.

关键词： Liquefaction hazard vulnerability risk assessment emergency routes

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Improving the Concentration of Students With Attention deficit Hyperactivity disorder and Autism Spectrum disorder: Electroencephalographic Analysis on the Effect of Learning Activity Interventions

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International Journal of Intelligent Technologies & Applied Statistics 2020年第1期13卷 49-63页

作者： Ming-Hseuh Tsai Sy-Ruen Huang Shao-Chin Chang Yu-Ling Lo Yun-Chieh Lu Research Center for Education Systems and Policy National Academy f or Educational Research New Taipei City Taiwan Chung Chou University of Science and Technology Changhua County Taiwan Ph.D. Program of Electrical and Communications Engineering Feng-Chia University Taichung City Taiwan Department of Early Childhood Education Asia University Taichung City Taiwan

This study examined whether the learning concentration of students with attention deficit hyperactivity disorder (AdHd) or autism spectrum disorder (ASd) can be improved through participation in one-on-one learning activities. A total of 13 students with AdHd or ASd were recruited to participate in various weekly one-on-one learning activities, in an effort to improve the concentration of students with special needs. Brainwave data were collected through electroencephalography and analyzed to explore students' concentration performance in different learning activities. To achieve the objective of this study, a multi-baseline design (ABAB), a type of single-subject design method, was employed. The experiment spanned 21 weeks, covering a fall and a spring semester: the first three weeks were defined as the 1st baseline phase, the 4th to 10th weeks as the 1st experimental phase, the 11th to 13th weeks as the 2nd baseline phase, and the 14th to 21th weeks as the 2nd experimental phase. The learning activities took place in the morning self-study period once a week, and the experiment was only suspended during two of the weeks because of school events. The purpose of the two baseline phases was to collect students' brainwave data. Students' brainwaves were measured for two minutes under two scenarios; first, while they were relaxed with eyes looking straight ahead; second, they were reading a passage. The purpose of the two experimental phases was to gradually enhance students' concentration by training them to perceive their own emotions through brainwave lamps. Initial results yielded different brainwave data for students with different types of disorders. After participating in the training on learning concentration, some students demonstrated improved concentration; however, after the 2nd experimental phase, students' concentration declined. The reason was that the activities in both experimental phases were identical, and thus, they no longer provoked students' inte

关键词： Attention def icit hyperactivity disorder (AdHd) Autism spectrum disorder (ASd) Brainwave test Concentration

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Integration of MRI and somatosensory evoked potentials facilitate diagnosis of spinal cord compression

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Scientific Reports 2023年第1期13卷 1-12页

作者： Sun, Shu-Pin phang, Chun-Ren Tzou, Shey-Cherng Chen, Chang-Mu Ko, Li-Wei International Ph.D. Program in Interdisciplinary Neuroscience (UST) College of Biological Science and Technology National Yang Ming Chiao Tung University 734 Engineering Bldg. 5 1001 Daxue Road Hsinchu 30010 Taiwan Department of Medical Research National Taiwan University Hospital Hsin-Chu Branch Hsinchu 300 Taiwan Institute of Molecular Medicine and Bioengineering National Yang Ming Chiao Tung University Hsinchu 300 Taiwan Department of Surgery College of Medicine and Hospital National Taiwan University No. 7 Zhongshan South Road Taipei 10002 Taiwan Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B) College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu 300 Taiwan Institute of Electrical and Control Engineering Department of Electronics and Electrical Engineering National Yang Ming Chiao Tung University Hsinchu 300 Taiwan Department of Biomedical Science and Environment Biology and the Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung 807 Taiwan

This study aimed to integrate magnetic resonance imaging (MRI) and related somatosensory evoked potential (SSEP) features to assist in the diagnosis of spinal cord compression (SCC). MRI scans were graded from 0 to 3 according to the changes in the subarachnoid space and scan signals to confirm differences in SCC levels. The amplitude, latency, and time–frequency analysis (TFA) power of preoperative SSEP features were extracted and the changes were used as standard judgments to detect neurological function changes. Then the patient distribution was quantified according to the SSEP feature changes under the same and different MRI compression grades. Significant differences were found in the amplitude and TFA power between MRI grades. We estimated three degrees of amplitude anomalies and power loss under each MRI grade and found the presence or absence of power loss occurs after abnormal changes in amplitude only. For SCC, few integrated approach combines the advantages of both MRI and evoked potentials. However, integrating the amplitude and TFA power changes of SSEP features with MRI grading can help in the diagnosis and speculate progression of SCC. © 2023, The Author(s).

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ITIH4 alleviates OVA-induced asthma by regulating lung-gut microbiota

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Molecular Medicine 2025年第1期31卷 1-13页

作者： Liu, Yi-Hsuan Lee, Yueh-Lun Han, Chia-Li Lo, Yu-Chun Liao, Zih-An Shih, Yu-Syuan Lin, Yi-Wen Peng, Syue-Wei Lee, Kang-Yun Ho, Shu-Chuan Wu, Sheng-Ming Lin, Cheng-Wei Chung, Kian Fan Chang, Jer-Hwa Chuang, Hsiao-Chi School of Respiratory Therapy College of Medicine Taipei Medical University 250 Wuxing Street Taipei 11031 Taiwan Department of Microbiology and Immunology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Master Program in Clinical Genomics and Proteomics College of Pharmacy Taipei Medical University Taipei Taiwan The Ph.D. Program for Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan Division of Pulmonary Medicine Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Division of Pulmonary Medicine Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan Department of Biochemistry and Molecular Cell Biology Taipei Medical University Taipei Taiwan National Heart and Lung Institute Imperial College London London United Kingdom Division of Pulmonary Medicine Department of Internal Medicine Wan Fang Hospital Taipei Medical University Taipei Taiwan Cell Physiology and Molecular Image Research Center Wan Fang Hospital Taipei Medical University Taipei Taiwan

Background: Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), a Type 2 acute phase protein, is critical for resolving inflammation and promoting tissue repair. While its role in chronic respiratory diseases is recognized, its effects on asthma remain unclear. This study investigated the effects of ITIH4 on the modulation of lung and gut microbiota, the attenuation of allergic inflammation, and the improvement of respiratory outcomes in an asthma mouse model. Methods: Six-week-old male Balb/c mice were divided into five groups: control, ITIH4, ovalbumin (OVA), and two OVA + ITIH4 treatment groups at different doses. Lung function and oxygen saturation were measured, and bronchoalveolar lavage fluid (BALF) was analyzed for white blood cell counts and cytokines. Lung and gut microbiota were profiled using 16 S rRNA gene sequencing, and short-chain fatty acids (SCFAs) were measured using gas chromatography-mass spectrometry (GC-MS). Proteomic profiling of intestinal tissues was conducted to identify ITIH4-associated signaling pathways. Results: ITIH4 administration significantly mitigated OVA-induced asthma symptoms by reducing weight loss, airway resistance, and tissue damping (p < 0.05). Histological analysis showed decreased airway wall thickening and lung injury scores (p < 0.05). ITIH4 also lowered BALF eosinophils and lymphocytes, IgE, and Th2 cytokines (IL-4, IL-5, and IL-13) (p < 0.05). ITIH4 treatment modulated microbiome composition, enriching Gram-positive taxa (Nocardioidaceae and Acholeplasmataceae) and depleting Gram-negative Helicobacteraceae (p < 0.05). SCFAs correlated with microbiome alterations, notably reduced 4-methylpentanoic acid levels (p < 0.05). Proteomic analysis revealed a dose-dependent activation of granzyme A signaling and suppression of metabolic and solute transport pathways. Conclusions: ITIH4 ameliorates asthma symptoms by modulating lung and gut microbiota, dampening Th2-driven inflammation, and restoring mucosal immune balance. Th

关键词： Airway hyperresponsiveness Inflammation Microbiome Short-chain fatty acid Th2

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different synaptic mechanisms of intermittent and continuous theta-burst stimulations in a severe foot-shock induced and treatment-resistant depression in a rat model

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Experimental Neurology 2023年第1期362卷 114338页

作者： Lee, Chi-Wei Chu, Ming-Chia Wu, Han-Fang Chung, Yueh-Jung Hsieh, Tsung-Han Chang, Chieh-Yu Lin, Yen-Cheng Lu, Ting-Yi Chang, Ching-Hsiang Chi, Hsiang Chang, Hsun-Shuo Chen, Yih-Fung Li, Cheng-Ta Lin, Hui-Ching Department and Institute of Physiology School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Department of Optometry Hsin-Sheng College of Medical Care and Management Taoyuan Taiwan School of Pharmacy College of Pharmacy Kaohsiung Medical University Kaohsiung Taiwan Department of Psychiatry Taipei Veterans General Hospital Taipei Taiwan Brain Research Center National Yang Ming Chiao Tung University Taipei Taiwan Institute of Brain Science National Yang Ming Chiao Tung University Taipei Taiwan Division of Psychiatry Faculty of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University and National Health Research Institute Taipei Taiwan

Treatment-resistant depression (TRd) is a condition wherein patients with depression fail to respond to antidepressant trials. A new form of repetitive transcranial magnetic stimulation (rTMS), called theta-burst stimulation (TBS), which includes intermittent theta-burst stimulation (iTBS) and continuous theta-burst stimulation (cTBS), is non-inferior to rTMS in TRd treatment. However, the mechanism of iTBS and cTBS underlying the treatment of TRd in the prefrontal cortex (PFC) remains unclear. Hence, we applied foot-shock stress as a traumatic event to develop a TRd rat model and investigated the different mechanisms of iTBS and cTBS. The iTBS and cTBS treatment were effective in depressive-like behavior and active coping behavior. The iTBS treatments improved impaired long-term potentiation and long-term depression (LTd), whereas the cTBS treatment only improved aberrant LTd. Moreover, the decrease in mature brain-derived neurotrophic factor (BdNF)-related protein levels were reversed by iTBS treatment. The decrease in proBdNF-related protein expression was improved by iTBS and cTBS treatment. Both iTBS and cTBS improved the decreased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and downregulation of mammalian target of the rapamycin (mTOR) signaling pathway. The iTBS produces both excitatory and inhibitory synaptic effects, and the cTBS only produces inhibitory synaptic effects in the PFC. © 2023

关键词： BdNF Continuous theta-burst stimulation Intermittent theta-burst stimulation Prefrontal cortex Synaptic plasticity Treatment-resistant depression

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Chemoresistance in acute myeloid leukemia: An alternative single-cell RNA sequencing approach

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Hematological oncology 2023年第3期41卷 499-509页

作者： Po-Liang Cheng Tzu-Hung Hsiao Chung-Hsing Chen Miao-Neng Hung Pei-Pei Jhan Li-Wen Lee Ting-Shuan Wu Jia-Rung Tsai Chieh-Lin Jerry Teng Department of Medical Research Taichung Veterans General Hospital Taichung Taiwan. Research Center for Biomedical Science and Engineering National Tsing Hua University Hsinchu Taiwan. Department of Public Health Fu Jen Catholic University New Taipei City Taiwan. Institute of Genomics and Bioinformatics National Chung Hsing University Taichung Taiwan. National Institute of Cancer Research National Health Research Institutes Zhunan Taiwan. Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan. Division of Hematology/Medical Oncology Department of Medicine Taichung Veterans General Hospital Taichung Taiwan. Department of Life Science Tunghai University Taichung Taiwan. School of Medicine Chung Shan Medical University Taichung Taiwan. Ph.D. Program in Translational Medicine National Chung Hsing University Taichung Taiwan. Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung Taiwan.

Our previous study demonstrated that myc, mitochondrial oxidative phosphorylation, mTOR, and stemness are independently responsible for chemoresistance in acute myeloid leukemia (AML) cells. This study aimed to identify potential mechanisms of chemoresistance of the "7 + 3" induction in AML by using a single-cell RNA sequencing (scRNA-seq) approach. In the present study, 13 untreated patients with de novo AML were enrolled and stratified into two groups: complete remission (CR; n = 8) and non-CR (n = 5). Single-cell RNA sequencing was used to analyze genetic profiles of 28,950 AML cells from these patients; results were validated using a previously published bulk RNA-seq dataset. Our study results showed chemoresistant AML cells had premature accumulation during early hematopoiesis. Hematopoietic stem cell-like cells from the non-CR group expressed more leukemic stem cell markers (Cd9, Cd82, IL3RA, and IL1RAP) than those from the CR group. Chemoresistant progenitor cells had impaired myeloid differentiation owing to early arrest of hematopoiesis. Notably, AML cells analyzed by scRNA-seq and bulk RNA-seq harbored a comparable myeloid lineage cell fraction, which internally validated our results. Using the TCGA database, our analysis demonstrated that patients with AML with higher expression of chemoresistant genetic markers (IL3RA and IL1RAP) had a worse overall survival (p < 0.01 for IL3RA; p < 0.05 for IL1RAP). In conclusion, AML cells responsive and resistant to the "7 + 3" induction were derived from a diverse cancerous hematopoietic stem cell population, as indicated by the specific genetic biomarkers obtained using scRNA-seq approach. Furthermore, arrest of hematopoiesis was shown to occur earlier in chemoresistant AML cells, furthering the current understanding of chemoresistance in AML.

关键词： acute myeloid leukemia chemoresistance leukemia stem cells single-cell RNA-seq

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