176 results on '"Ching-Cheng Huang"'
Search Results
52. Rpl13a small nucleolar RNAs regulate systemic glucose metabolism
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Daniel S. Ory, Maria S. Remedi, Alexis N. Harris, Jean E. Schaffer, Jana Mahadevan, Zeno Lavagnino, Christopher L. Holley, Fumihiko Urano, Hideji Fujiwara, Kelly D. Pyles, David E. Scherrer, Rohini Sidhu, David W. Piston, Stanley Ching-Cheng Huang, Jiyeon Lee, and Jessie Zhang
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Ribosomal Proteins ,0301 basic medicine ,Mitochondrion ,Biology ,medicine.disease_cause ,Diabetes Mellitus, Experimental ,Islets of Langerhans ,Mice ,03 medical and health sciences ,Ribosomal protein ,RNA, Small Nuclear ,medicine ,Animals ,Small nucleolar RNA ,Ribonucleoprotein ,Mice, Knockout ,urogenital system ,Pancreatic islets ,Intron ,General Medicine ,Ribosomal RNA ,Introns ,Mitochondria ,Oxidative Stress ,Glucose ,030104 developmental biology ,medicine.anatomical_structure ,Biochemistry ,Reactive Oxygen Species ,Oxidative stress ,Research Article - Abstract
Small nucleolar RNAs (snoRNAs) are non-coding RNAs that form ribonucleoproteins to guide covalent modifications of ribosomal and small nuclear RNAs in the nucleus. Recent studies have also uncovered additional non-canonical roles for snoRNAs. However, the physiological contributions of these small RNAs are largely unknown. Here, we selectively deleted four snoRNAs encoded within the introns of the ribosomal protein L13a (Rpl13a) locus in a mouse model. Loss of Rpl13a snoRNAs altered mitochondrial metabolism and lowered reactive oxygen species tone, leading to increased glucose-stimulated insulin secretion from pancreatic islets and enhanced systemic glucose tolerance. Islets from mice lacking Rpl13a snoRNAs demonstrated blunted oxidative stress responses. Furthermore, these mice were protected against diabetogenic stimuli that cause oxidative stress damage to islets. Our study illuminates a previously unrecognized role for snoRNAs in metabolic regulation.
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- 2016
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53. Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming
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Stanley Ching-Cheng Huang, Daniel Braas, Angelika S. Rambold, Christina M. O’Neill, David E. Sanin, Edward J. Pearce, Jing Qiu, Michael D. Buck, Tobias B. Huber, Oliver Kretz, David O’Sullivan, Gerritje J.W. van der Windt, Ramon I. Klein Geltink, Chih-Hao Chang, Brian T. Edelson, Hiromi Sesaki, Erika L. Pearce, Jonathan D. Curtis, Qiongyu Chen, and Experimental Immunology
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0301 basic medicine ,T-Lymphocytes ,T cell ,Cellular differentiation ,Cell ,Oxidative phosphorylation ,Mitochondrion ,Biology ,Mitochondrial Dynamics ,General Biochemistry, Genetics and Molecular Biology ,GTP Phosphohydrolases ,Electron Transport ,Mice ,03 medical and health sciences ,medicine ,Animals ,Humans ,Beta oxidation ,Catabolism ,Fatty Acids ,Cell Differentiation ,Research Highlight ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Anaerobic glycolysis ,Glycolysis ,Immunologic Memory ,Oxidation-Reduction ,Signal Transduction - Abstract
Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, by altering cristae morphology, fusion in TM cells configures electron transport chain (ETC) complex associations favoring oxidative phosphorylation (OXPHOS) and FAO, while fission in TE cells leads to cristae expansion, reducing ETC efficiency and promoting aerobic glycolysis. Thus, mitochondrial remodeling is a signaling mechanism that instructs T cell metabolic programming.
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- 2016
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54. Navigating metabolic pathways to enhance antitumour immunity and immunotherapy
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Pedro Romero, Mathias Wenes, Sarah-Maria Fendt, Ping-Chih Ho, Stanley Ching-Cheng Huang, and Xiaoyun Li
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0301 basic medicine ,T cell ,medicine.medical_treatment ,Context (language use) ,Antineoplastic Agents ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Neoplasms ,Tumor Microenvironment ,Medicine ,Humans ,business.industry ,Drug Repositioning ,Cancer ,Drug Synergism ,Immunotherapy ,medicine.disease ,Combined Modality Therapy ,3. Good health ,Immunosurveillance ,Drug repositioning ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,business ,Reprogramming ,Metabolic Networks and Pathways - Abstract
The development of immunotherapies over the past decade has resulted in a paradigm shift in the treatment of cancer. However, the majority of patients do not benefit from immunotherapy, presumably owing to insufficient reprogramming of the immunosuppressive tumour microenvironment (TME) and thus limited reinvigoration of antitumour immunity. Various metabolic machineries and nutrient-sensing mechanisms orchestrate the behaviour of immune cells in response to nutrient availability in the TME. Notably, tumour-infiltrating immune cells typically experience metabolic stress as a result of the dysregulated metabolic activity of tumour cells, leading to impaired antitumour immune responses. Moreover, the immune checkpoints that are often exploited by tumour cells to evade immunosurveillance have emerging roles in modulating the metabolic and functional activity of T cells. Thus, repurposing of drugs targeting cancer metabolism might synergistically enhance immunotherapy via metabolic reprogramming of the TME. In addition, interventions targeting the metabolic circuits that impede antitumour immunity have been developed, with several clinical trials underway. Herein, we discuss how these metabolic circuits regulate antitumour immunity and the possible approaches to targeting these pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments that could be used to better unleash the potential of adoptive cell therapies by enhancing T cell metabolism. ispartof: NATURE REVIEWS CLINICAL ONCOLOGY vol:16 issue:7 pages:425-441 ispartof: location:England status: published
- Published
- 2019
55. Biological and Preclinical Evaluations of Designed Optically Guided Medical Devices with Light Scattering Modules for Carpal Tunnel Syndrome Treatment and Surgical Procedure
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Ming-Che Chiang and Ching-Cheng Huang
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medicine.medical_specialty ,Chemistry ,InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL ,medicine ,Radiology ,Carpal tunnel syndrome ,medicine.disease ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Light scattering - Published
- 2019
56. Good Water Absorption and Anti-adhesion Properties of Designed Extra Thin PVA Foam Membranes with Fully Open-cell Microstructures Derived from a Super Clean Air-Foaming Process with Active Molecules for Minimally Invasive Surgery
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K-G Gaßmann, Meng Jen Yang, and Ching Cheng Huang
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chemistry.chemical_compound ,Membrane ,Materials science ,Absorption of water ,chemistry ,Invasive surgery ,Molecule ,General Medicine ,Composite material ,Microstructure ,Polyvinyl alcohol ,Anti adhesion ,Polyurethane - Abstract
The design of medical devices could be applied and developed for new microscopic surgical procedures instead of the traditional surgical procedures.
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- 2019
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57. Preparation of New Acellular Dermal Collagen Scaffolds via Combination of Phytoproteinases and Supercritical Carbon Dioxide Treatments
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Tzu-hung Su, Ing-Lin Chang, Meng-Jen Yang, Wang-Yao Wu, Kuan-Ta Chen, Ching-Cheng Huang, and Tse-wei Ciou
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Dermal collagen ,Supercritical carbon dioxide ,Chemical engineering ,Chemistry - Published
- 2019
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58. Design and Preparation of Novel Cross-linked Polyvinyl Alcohol Extra Permeable Foam Dressings for NPWT via a Combined Process of Super Clean Air foaming and Ultra Precision Machining
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Ing-Lin Chang, Meng-Jen Yang, and Ching-Cheng Huang
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chemistry.chemical_compound ,Matrix (mathematics) ,Materials science ,Machining ,chemistry ,Scientific method ,Composite material ,Ultra precision ,Polyvinyl alcohol - Published
- 2019
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59. Characteristics and Micromorphology of Designed Regenerative a Cellular Dermal Collagen Particles Derived from a Combined Procedure of Supercritical Carbon Dioxide Fluids and Protease Treatments at Low Temperatures
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Ching Cheng Huang
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Dermal collagen ,Supercritical carbon dioxide ,Protease ,Chemical engineering ,Chemistry ,medicine.medical_treatment ,medicine ,Combined procedure - Abstract
A new regenerative collagen particle with extra-cellular matrix (ECM) was designed and prepared from porcine dermal. A specific tissue-cutting machine was designed to prepare extra thin tissue membranes, which could be used for preparing the regenerative collagen particles with ECM. Furthermore, a novel procedure combining supercritical carbon dioxide fluids technology and protease treatments at low temperatures was employed. Characteristics of the resulting regenerative collagen particles with ECM were observed by determining morphology, thermal property and mechanical property for clinic application of medical devices
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- 2019
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60. Collagen Films with Extra Cellular Matrix via Combination of Supercritical Carbon Dioxide Fluid and NH4OH Treatments
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Yu-Lin Shen, Ciao-Yi Syu, Meng-Jen Yang, Cong-Han Xiao, Ing-Lin Chang, Hsiao-Chih Hu, and Ching-Cheng Huang
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Extracellular matrix ,Supercritical carbon dioxide ,Chemical engineering ,Chemistry - Published
- 2019
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61. Characteristics and Micromorphology of New Collagen Scaffolds Derived from Supercritical Fluid of Carbon Dioxide with Alcohol Cosolvents
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Cong-Han Xiao, Ing-Lin Chang, Ciao-Yi Syu, Yi-hung Ho, Yu-Lin Shen, Ching-Cheng Huang, and Meng-Jen Yang
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chemistry.chemical_compound ,chemistry ,Chemical engineering ,Carbon dioxide ,Alcohol ,Supercritical fluid - Published
- 2019
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62. Design and Preparation of Novel Anti-adhesion Polyvinyl Alcohol Foam Nasal Matrix for PM 2.5 Protecting and Hemostasis Treatments via a Combined Procedure of Precision Machining and Super Clean Air-foaming
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Huan Zhou, Meng-Jen Yang, Lei Yang, and Ching-Cheng Huang
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Matrix (chemical analysis) ,Materials science ,Machining ,Hemostasis ,Polyvinyl alcohol foam ,Combined procedure ,Composite material ,Anti adhesion - Published
- 2019
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63. Design and Preparation of Novel Anti-adhesion Extra Thin Polyvinyl Alcohol Foam Dressings for NPWT via a Combined Procedure of Ultra Precision Machining and Super Clean Air-foaming
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Zhiguo Zhang, Meng-Jen Yang, Ching-Cheng Huang, and Ing-Lin Chang
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Matrix (chemical analysis) ,Materials science ,Machining ,Polyvinyl alcohol foam ,Combined procedure ,Composite material ,Ultra precision ,Anti adhesion - Published
- 2019
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64. Optically-guided scalpel with light-scattering module for carpal tunnel surgical procedure via minimally invasive surgery
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Ching-Cheng Huang and Ming-Che Chiang
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musculoskeletal diseases ,Novel technique ,Microsurgery ,medicine.medical_specialty ,Engineering ,Light ,Swine ,medicine.medical_treatment ,Biomedical Engineering ,Biomaterials ,medicine ,Animals ,Humans ,Minimally Invasive Surgical Procedures ,Scattering, Radiation ,Carpal tunnel ,Carpal tunnel syndrome ,Lighting ,Biological evaluation ,business.industry ,Optical Devices ,Equipment Design ,General Medicine ,Surgical procedures ,medicine.disease ,Carpal Tunnel Syndrome ,Surgery ,Equipment Failure Analysis ,body regions ,medicine.anatomical_structure ,Surgery, Computer-Assisted ,Invasive surgery ,Catheter Ablation ,business ,Clinical evaluation ,Biomedical engineering - Abstract
A novel technique and product for carpal tunnel microscopic surgical procedures using a modified medical device containing a head as a surgical scalpel under light guidance were designed and studied. The novel design of the medical device was developed and applied in a new carpal tunnel microscopic surgical procedure in place of the traditional carpal tunnel surgical procedure. Biological and clinical evaluations of carpal tunnel surgical procedure using the designed optically guided medical device were studied. For commercialized reasons, some guidance was considered, such as ISO 10993-1:2009(E), for the biological evaluation of the device. Furthermore, a clinical evaluation was carried out. The designed optically guided medical device could provide a powerful medical device for carpal tunnel syndrome and related applications.
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- 2015
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65. The metabolic control of schistosome egg production
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Edward J. Pearce and Stanley Ching-Cheng Huang
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biology ,Transmission (medicine) ,Ecology ,Host (biology) ,Immunology ,Zoology ,Tropical disease ,Schistosomiasis ,Disease ,medicine.disease ,biology.organism_classification ,Microbiology ,Sexual dimorphism ,Immune system ,Virology ,medicine ,Schistosoma - Abstract
Schistosomiasis is a neglected tropical disease caused by infection with trematode parasites of the genus Schistosoma. Despite ongoing treatment programmes, the prevalence of schistosomiasis has failed to decline and the disease remains a cause of severe morbidity in millions of people. Understanding the biology of egg production by schistosomes is critical since eggs allow transmission of the infection, and when trapped in host tissues induce the immune responses that are responsible for the pathologic changes that underlie disease development. Unusually among trematodes, adult schistosomes exhibit sexual dimorphism and display a fascinating codependency in that the female is dependent on the male to grow and sexually mature. Thus, virgin females are developmentally stunted compared with females from mixed-sex infections and are unable to lay eggs. Moreover, fecund female schistosomes rapidly lose the ability to produce eggs when placed in tissue culture. Here we discuss the metabolic regulation of egg production in schistosomes, and in particular the critical role played by fatty acid oxidation in this process.
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- 2015
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66. Characterization of titanium dioxide and zinc oxide nanoparticles in sunscreen powder by comparing different measurement methods
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S.W. Fang, Stanley Ching-Cheng Huang, Hwei-Fang Cheng, W. L. Cheng, Pei-Jia Lu, and M.C. Huang
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Materials science ,Oxide ,Nanoparticle ,chemistry.chemical_element ,Metal Nanoparticles ,lcsh:TX341-641 ,02 engineering and technology ,Zinc ,010402 general chemistry ,01 natural sciences ,Mass Spectrometry ,Matrix (chemical analysis) ,chemistry.chemical_compound ,Microscopy, Electron, Transmission ,X-Ray Diffraction ,Particle Size ,Pharmacology ,Titanium ,lcsh:RM1-950 ,021001 nanoscience & nanotechnology ,Copper ,0104 chemical sciences ,lcsh:Therapeutics. Pharmacology ,chemistry ,Chemical engineering ,Titanium dioxide ,Particle ,Inductively coupled plasma ,Powders ,Zinc Oxide ,0210 nano-technology ,lcsh:Nutrition. Foods and food supply ,Sunscreening Agents ,Food Science - Abstract
Numerous consumer products, such as cosmetics, contain nanoparticles (NPs) of titanium dioxide (TiO2) or zinc oxide (ZnO); however, this raises questions concerning the safety of such additives. Most of these products do not indicate whether the product includes NPs. In this study, we characterized metal oxide NPs according to size, shape, and composition as well as their aggregation/agglomeration characteristics. In order to comprehend quickly the characterization of metal oxide NPs, we employed single particle inductively coupled plasma (SP-ICPMS) to help quantify the size of metal oxide NPs; then, we use transmission electron microscopy (TEM) to corroborate the results. The crystal size and structure was measured by X-ray diffraction (XRD), there are two crystal phase of TiO2 NPs in sunscreen powder showed in XRD. However, SP-ICPMS proved highly effective in determining the size of NPs, the results of which remarkably good agreement with the TEM measurements. Pre-treatment included a conventional copper grid (requiring sample dilution) to evaluate the size, shape and composition of primary particles or plastic embedding (without the need for sample dilution) to evaluate the aggregate/aggregation of native NOAAs. The proposed method is an effective and fast approach to the characterization of oxide NPs in cosmetic sunscreen powder. These findings outline an alternative approach to the analysis of NPs in powder-form matrix. Keywords: Sunscreen powder, Nanoparticles, Titanium dioxide, Zinc oxide, Single particle inductively coupled plasma
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- 2017
67. TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease
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David M. Holtzman, Yaming Wang, Susan Gilfillan, Alexander A. Loboda, Stanley Ching-Cheng Huang, Herbert W. Virgin, Wilbur M. Song, Marina Cella, Ekaterina Loginicheva, Amal Kambal, Tyler K. Ulland, Emil R. Unanue, Alexey Sergushichev, Jason D. Ulrich, Yingyue Zhou, Nigel J. Cairns, Maxim N. Artyomov, Wandy L. Beatty, and Marco Colonna
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0301 basic medicine ,medicine.medical_specialty ,Plaque, Amyloid ,Biology ,AMP-Activated Protein Kinases ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Mice ,Alzheimer Disease ,Internal medicine ,medicine ,Autophagy ,Neurites ,Animals ,Humans ,Lectins, C-Type ,Receptors, Immunologic ,Receptor ,PI3K/AKT/mTOR pathway ,Membrane Glycoproteins ,Microglia ,TREM2 ,Endoplasmic reticulum ,Macrophages ,TOR Serine-Threonine Kinases ,Neurodegeneration ,medicine.disease ,Cell biology ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Creatinine ,Energy Metabolism ,Intracellular - Abstract
Elevated risk of developing Alzheimer's disease (AD) is associated with hypomorphic variants of TREM2, a surface receptor required for microglial responses to neurodegeneration, including proliferation, survival, clustering, and phagocytosis. How TREM2 promotes such diverse responses is unknown. Here, we find that microglia in AD patients carrying TREM2 risk variants and TREM2-deficient mice with AD-like pathology have abundant autophagic vesicles, as do TREM2-deficient macrophages under growth-factor limitation or endoplasmic reticulum (ER) stress. Combined metabolomics and RNA sequencing (RNA-seq) linked this anomalous autophagy to defective mammalian target of rapamycin (mTOR) signaling, which affects ATP levels and biosynthetic pathways. Metabolic derailment and autophagy were offset in vitro through Dectin-1, a receptor that elicits TREM2-like intracellular signals, and cyclocreatine, a creatine analog that can supply ATP. Dietary cyclocreatine tempered autophagy, restored microglial clustering around plaques, and decreased plaque-adjacent neuronal dystrophy in TREM2-deficient mice with amyloid-β pathology. Thus, TREM2 enables microglial responses during AD by sustaining cellular energetic and biosynthetic metabolism.
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- 2017
68. Carbohydrate and Amino Acid Metabolism as Hallmarks for Innate Immune Cell Activation and Function
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Haoxin Zhao, Stanley Ching-Cheng Huang, and Lydia N. Raines
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immunometabolism ,carbohydrates ,Review ,Biology ,Models, Biological ,Immune system ,Animals ,Humans ,lcsh:QH301-705.5 ,innate immunity ,chemistry.chemical_classification ,amino acids ,Innate immune system ,Myeloid-Derived Suppressor Cells ,fungi ,food and beverages ,General Medicine ,Metabolism ,biochemical phenomena, metabolism, and nutrition ,Carbohydrate ,Phenotype ,Immunity, Innate ,Cell biology ,Amino acid ,lcsh:Biology (General) ,chemistry ,bacteria ,Carbohydrate Metabolism ,Cell activation ,Function (biology) - Abstract
Immune activation is now understood to be fundamentally linked to intrinsic and/or extrinsic metabolic processes which are essential for immune cells to survive, proliferate, and perform their effector functions. Moreover, disruption or dysregulation of these pathways can result in detrimental outcomes and underly a number of pathologies in both communicable and non-communicable diseases. In this review, we discuss how the metabolism of carbohydrates and amino acids in particular can modulate innate immunity and how perturbations in these pathways can result in failure of these immune cells to properly function or induce unfavorable phenotypes.
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- 2020
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69. Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter
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Tiffany A. Reese, Gautam Goel, Maxim N. Artyomov, Stanley Ching-Cheng Huang, Samuel H. Speck, Catherine Y. Liu, Matthew M. Hufford, Andrew J. Jezewski, Xin Zhang, Michael D. Buck, Brian S. Wakeman, Mark H. Kaplan, Edward J. Pearce, Ramnik J. Xavier, Rolf Renne, Amal Kambal, Peter J. Murray, H.S. Choi, and Herbert W. Virgin
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Multidisciplinary ,viruses ,medicine.medical_treatment ,Promoter ,Biology ,biology.organism_classification ,medicine.disease ,Virology ,Article ,Transactivation ,Cytokine ,Viral replication ,Virus latency ,medicine ,Gammaherpesvirinae ,Interferon gamma ,Interleukin 4 ,medicine.drug - Abstract
Parasites make it hard to fight viruses Microbial co-infections challenge the immune system—different pathogens often require different flavors of immune responses for their elimination or containment (see the Perspective by Maizels and Gause). Two teams studied what happens when parasitic worms and viruses infect mice at the same time. Reese et al. found that parasite co-infection woke up a dormant virus. Osborne et al. found that mice already infected with parasitic worms were worse at fighting off viruses. In both cases, worms skewed the immune response so that the immune cells and the molecules they secreted created an environment favorable for the worm at the expense of antiviral immunity. Science , this issue p. 573 and p. 578 ; see also p. 517
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- 2014
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70. Designed drug-release systems having various breathable polyurethane film-backed hydrocolloid acrylated adhesive layers for moisture healing
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Ching-Cheng Huang, Hsia-Wei Liu, and Ching-Hsien Chang
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Materials science ,Polyurethanes ,Biomedical Engineering ,Moisture permeability ,Permeability ,Biomaterials ,chemistry.chemical_compound ,Adhesives ,Materials Testing ,Animals ,Humans ,Colloids ,Interpenetrating polymer network ,Composite material ,Sodium alginate ,Polyurethane ,Wound Healing ,Moisture ,Adhesiveness ,Water ,Membranes, Artificial ,Equipment Design ,General Medicine ,Bandages ,Equipment Failure Analysis ,Acrylates ,chemistry ,Delayed-Action Preparations ,Drug release ,Adsorption ,Adhesive ,Layer (electronics) - Abstract
A series of designed drug-release systems were prepared and established for clear moisture healing. These systems were designed to have an interpenetrating polymer network (IPN) structure, which contained a breathable polyurethane film, hydrocolloidlayer, and polyacrylate adhesive layer. Breathable polyurethane film (2000 g/m(2)/24 hr) with high moisture permeability was employed as a base for new drug-release systems or wound dressings. All drug-release systems having a polyurethane film-backed hydrocolloid acrylated adhesive layer showed an increase of water uptakes with increasing time. After 114 hours, high water uptakes of drug-release systems with 20% hydrocolloid components were observed in the values of 160, 1100, and 1870% for different additional hydrocolloid components of carboxymethylcellulose, sodium alginate, and carbomer U10, respectively. New drug-release systems of polyurethane film-backed hydrocolloid/adhesive layers could be designed and established for wound care managements.
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- 2014
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71. CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability
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Edward J. Pearce, Michael D. Buck, Teresa Ai, Gerritje J.W. van der Windt, Bart Everts, Amber M. Smith, Stanley Ching-Cheng Huang, Jonathan D. Curtis, Erika L. Pearce, Russell G. Jones, Chih-Hao Chang, David O’Sullivan, Brandon Faubert, and Experimental Immunology
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Hexokinase ,Multidisciplinary ,Bioenergetics ,Effector ,Oxidative phosphorylation ,CD8-Positive T-Lymphocytes ,Biological Sciences ,Mitochondrion ,Biology ,Lymphocyte Activation ,Cell biology ,Mice ,chemistry.chemical_compound ,Biochemistry ,chemistry ,Anaerobic glycolysis ,Animals ,Glycolysis ,Mitochondrial Size ,Energy Metabolism ,Immunologic Memory ,CD8 - Abstract
A characteristic of memory T (T M ) cells is their ability to mount faster and stronger responses to reinfection than naïve T (T N ) cells do in response to an initial infection. However, the mechanisms that allow this rapid recall are not completely understood. We found that CD8 T M cells have more mitochondrial mass than CD8 T N cells and, that upon activation, the resulting secondary effector T (T E ) cells proliferate more quickly, produce more cytokines, and maintain greater ATP levels than primary effector T cells. We also found that after activation, T M cells increase oxidative phosphorylation and aerobic glycolysis and sustain this increase to a greater extent than T N cells, suggesting that greater mitochondrial mass in T M cells not only promotes oxidative capacity, but also glycolytic capacity. We show that mitochondrial ATP is essential for the rapid induction of glycolysis in response to activation and the initiation of proliferation of both T N and T M cells. We also found that fatty acid oxidation is needed for T M cells to rapidly respond upon restimulation. Finally, we show that dissociation of the glycolysis enzyme hexokinase from mitochondria impairs proliferation and blocks the rapid induction of glycolysis upon T-cell receptor stimulation in T M cells. Our results demonstrate that greater mitochondrial mass endows T M cells with a bioenergetic advantage that underlies their ability to rapidly recall in response to reinfection.
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- 2013
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72. Metabolic Reprogramming Mediated by the mTORC2-IRF4 Signaling Axis Is Essential for Macrophage Alternative Activation
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Erika L. Pearce, Joel D. Schilling, Bart Everts, Amber M. Smith, Edward J. Pearce, Marco Colonna, and Stanley Ching-Cheng Huang
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0301 basic medicine ,Macrophage colony-stimulating factor ,Immunology ,Mechanistic Target of Rapamycin Complex 2 ,Oxidative phosphorylation ,Biology ,Article ,Mice ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,Animals ,Immunology and Allergy ,Glycolysis ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Interleukin 4 ,Macrophage Colony-Stimulating Factor ,Macrophages ,TOR Serine-Threonine Kinases ,Macrophage Activation ,Cell biology ,030104 developmental biology ,Infectious Diseases ,Multiprotein Complexes ,Interferon Regulatory Factors ,Phosphorylation ,Interleukin-4 ,Signal transduction ,STAT6 Transcription Factor ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Macrophage activation status is intrinsically linked to metabolic remodeling. Macrophages stimulated by interleukin 4 (IL-4) to become alternatively (or, M2) activated increase fatty acid oxidation and oxidative phosphorylation; these metabolic changes are critical for M2 activation. Enhanced glucose utilization is also characteristic of the M2 metabolic signature. Here, we found that increased glucose utilization is essential for M2 activation. Increased glucose metabolism in IL-4-stimulated macrophages required the activation of the mTORC2 pathway, and loss of mTORC2 in macrophages suppressed tumor growth and decreased immunity to a parasitic nematode. Macrophage colony stimulating factor (M-CSF) was implicated as a contributing upstream activator of mTORC2 in a pathway that involved PI3K and AKT. mTORC2 operated in parallel with the IL-4Rα-Stat6 pathway to facilitate increased glycolysis during M2 activation via the induction of the transcription factor IRF4. IRF4 expression required both mTORC2 and Stat6 pathways, providing an underlying mechanism to explain how glucose utilization is increased to support M2 activation.
- Published
- 2016
73. TPL-2 Regulates Macrophage Lipid Metabolism and M2 Differentiation to Control TH2-Mediated Immunopathology
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Steven C. Ley, Stanley Ching-Cheng Huang, Mark S. Wilson, Edward J. Pearce, Nuha R. Mansour, Hania Khoury, Lewis J. Entwistle, Luiz Pedro S. de Carvalho, Yashaswini Kannan, Jimena Perez-Lloret, Stamatia Papoutsopoulou, Radma Mahmood, and Yanda Li
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0301 basic medicine ,Schistosoma Mansoni ,Cellular differentiation ,Gene Expression ,Pathology and Laboratory Medicine ,Biochemistry ,Mice ,White Blood Cells ,Animal Cells ,Fibrosis ,Immunopathology ,Medicine and Health Sciences ,Macrophage ,Immune Response ,lcsh:QH301-705.5 ,Mice, Knockout ,Cell Differentiation ,MAP Kinase Kinase Kinases ,M2 Macrophage ,Lipids ,3. Good health ,Cell biology ,Schistosoma ,Schistosoma mansoni ,Cellular Types ,medicine.symptom ,Research Article ,lcsh:Immunologic diseases. Allergy ,Lipolysis ,Immune Cells ,Immunology ,Inflammation ,Biology ,Microbiology ,03 medical and health sciences ,Th2 Cells ,Signs and Symptoms ,Extraction techniques ,Diagnostic Medicine ,Proto-Oncogene Proteins ,Helminths ,Virology ,Genetics ,medicine ,Animals ,T Helper Cells ,Molecular Biology ,Blood Cells ,MAP kinase kinase kinase ,Macrophages ,Organisms ,Biology and Life Sciences ,Cell Biology ,Lipid Metabolism ,medicine.disease ,biology.organism_classification ,Invertebrates ,Schistosomiasis mansoni ,RNA extraction ,Research and analysis methods ,Metabolism ,030104 developmental biology ,lcsh:Biology (General) ,Parasitology ,lcsh:RC581-607 ,Developmental Biology - Abstract
Persistent TH2 cytokine responses following chronic helminth infections can often lead to the development of tissue pathology and fibrotic scarring. Despite a good understanding of the cellular mechanisms involved in fibrogenesis, there are very few therapeutic options available, highlighting a significant medical need and gap in our understanding of the molecular mechanisms of TH2-mediated immunopathology. In this study, we found that the Map3 kinase, TPL-2 (Map3k8; Cot) regulated TH2-mediated intestinal, hepatic and pulmonary immunopathology following Schistosoma mansoni infection or S. mansoni egg injection. Elevated inflammation, TH2 cell responses and exacerbated fibrosis in Map3k8 –/–mice was observed in mice with myeloid cell-specific (LysM) deletion of Map3k8, but not CD4 cell-specific deletion of Map3k8, indicating that TPL-2 regulated myeloid cell function to limit TH2-mediated immunopathology. Transcriptional and metabolic assays of Map3k8 –/–M2 macrophages identified that TPL-2 was required for lipolysis, M2 macrophage activation and the expression of a variety of genes involved in immuno-regulatory and pro-fibrotic pathways. Taken together this study identified that TPL-2 regulated TH2-mediated inflammation by supporting lipolysis and M2 macrophage activation, preventing TH2 cell expansion and downstream immunopathology and fibrosis., Author Summary Chronic helminth infections can cause significant morbidity and organ damage in their definitive mammalian hosts. Managing this collateral damage can reduce morbidity and preserve vital tissues for normal organ function. One particular consequence of some chronic helminth infections is the deposition of fibrotic scar tissue, following immune responses directed towards helminth material. In this study we tested the role of a particular signalling kinase, TPL-2, and identified that it critically regulated the magnitude of fibrotic scarring following infection. Using several murine models with genetic deletions of TPL-2 in either all cells or specific deletion in subsets of immune cells (Map3k8 –/– Map3k8 fl/fl) we identified that expression of TPL-2 in myeloid cells was essential to prevent severe immune-mediated pathology. Using genome-wide analyses and metabolic assays, we discovered that TPL-2 was required for normal lipid metabolism and appropriate activation of myeloid cells / macrophages to limit fibrosis. These results revealed a previously unappreciated role for TPL-2 in preventing severe pathology following infection. Thus, activating this pathway may limit immune mediated pathology following chronic helminth infection. More broadly, this pathway is being targeted to treat inflammatory diseases and cancer [1, 2]. This study would suggest that caution should be taken to prevent untoward co-morbidities and fibrosis-related pathologies in patients when targeting TPL-2.
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- 2016
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74. Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation
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Edward J. Pearce, Monika Bambouskova, Maxim N. Artyomov, Russell G. Jones, Luisa Cervantes-Barragan, Vicky Lampropoulou, Emma E. Vincent, Alexey Sergushichev, Ekaterina Loginicheva, Gwendalyn J. Randolph, Stanley Ching-Cheng Huang, Michael S. Diamond, Shabaana A. Khader, Abhinav Diwan, Carla J. Weinheimer, Takla Griss, Xiucui Ma, and Sharmila Nair
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Lipopolysaccharides ,0301 basic medicine ,Physiology ,medicine.medical_treatment ,Cell Respiration ,Succinic Acid ,Regulator ,Inflammation ,Endogeny ,Biology ,Article ,03 medical and health sciences ,medicine ,Journal Article ,Animals ,Macrophage ,Molecular Biology ,Macrophages ,Succinate dehydrogenase ,Succinates ,Cell Biology ,Metabolism ,Macrophage Activation ,Mitochondria ,Mice, Inbred C57BL ,Succinate Dehydrogenase ,030104 developmental biology ,Cytokine ,Biochemistry ,Reperfusion Injury ,biology.protein ,Aconitate decarboxylase ,Female ,medicine.symptom ,Reactive Oxygen Species - Abstract
Summary Remodeling of the tricarboxylic acid (TCA) cycle is a metabolic adaptation accompanying inflammatory macrophage activation. During this process, endogenous metabolites can adopt regulatory roles that govern specific aspects of inflammatory response, as recently shown for succinate, which regulates the pro-inflammatory IL-1β-HIF-1α axis. Itaconate is one of the most highly induced metabolites in activated macrophages, yet its functional significance remains unknown. Here, we show that itaconate modulates macrophage metabolism and effector functions by inhibiting succinate dehydrogenase-mediated oxidation of succinate. Through this action, itaconate exerts anti-inflammatory effects when administered in vitro and in vivo during macrophage activation and ischemia-reperfusion injury. Using newly generated Irg1 −/− mice, which lack the ability to produce itaconate, we show that endogenous itaconate regulates succinate levels and function, mitochondrial respiration, and inflammatory cytokine production during macrophage activation. These studies highlight itaconate as a major physiological regulator of the global metabolic rewiring and effector functions of inflammatory macrophages.
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- 2016
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75. Mitochondrial Membrane Potential Regulates Nuclear Gene Expression in Macrophages Exposed to Prostaglandin E2
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Simon J. Lawless, Fabian Hässler, Stanley Ching-Cheng Huang, Michael D. Buck, Francesc Baixauli, Ramon I. Klein Geltink, Erika L. Pearce, Annette E. Patterson, Christina M. O’Neill, Katarzyna M. Grzes, David E. Sanin, Jing Qiu, David O’Sullivan, Jonathan D. Curtis, Duojiao Wu, Mai Matsushita, Mauro Corrado, Edward J. Pearce, Matteo Villa, Nikki van Teijlingen Bakker, Alanna M. Cameron, Agnieszka M. Kabat, and Gerhard Mittler
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0301 basic medicine ,Immunology ,Mitochondrion ,Biology ,Dinoprostone ,ETV1 ,Mice ,03 medical and health sciences ,Mediator ,medicine ,Transcriptional regulation ,Animals ,Humans ,Immunology and Allergy ,Prostaglandin E2 ,Transcription factor ,Gene ,Cells, Cultured ,Cell Nucleus ,Membrane Potential, Mitochondrial ,Gene Expression Profiling ,Macrophages ,Macrophage Activation ,Cell cycle ,Cell biology ,DNA-Binding Proteins ,Mice, Inbred C57BL ,HEK293 Cells ,030104 developmental biology ,Infectious Diseases ,Gene Expression Regulation ,NIH 3T3 Cells ,Interleukin-4 ,Signal Transduction ,Transcription Factors ,medicine.drug - Abstract
Metabolic engagement is intrinsic to immune cell function. Prostaglandin E2 (PGE2) has been shown to modulate macrophage activation, yet how PGE2 might affect metabolism is unclear. Here, we show that PGE2 caused mitochondrial membrane potential (Δψm) to dissipate in interleukin-4-activated (M(IL-4)) macrophages. Effects on Δψm were a consequence of PGE2-initiated transcriptional regulation of genes, particularly Got1, in the malate-aspartate shuttle (MAS). Reduced Δψm caused alterations in the expression of 126 voltage-regulated genes (VRGs), including those encoding resistin-like molecule α (RELMα), a key marker of M(IL-4) cells, and genes that regulate the cell cycle. The transcription factor ETS variant 1 (ETV1) played a role in the regulation of 38% of the VRGs. These results reveal ETV1 as a Δψm-sensitive transcription factor and Δψm as a mediator of mitochondrial-directed nuclear gene expression.
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- 2018
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76. Activation of Nippostrongylus brasiliensis infective larvae is regulated by a pathway distinct from the hookworm Ancylostoma caninum
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Glyn Ball, Danielle J. Smyth, Stanley Ching Cheng Huang, Murray E. Selkirk, Denice Tsz Yau Chan, and Kleoniki Gounaris
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Male ,Ancylostoma ,Population ,Ancylostomiasis ,Microbiology ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Cytochrome P-450 Enzyme System ,parasitic diseases ,Animals ,Humans ,Secretion ,LY294002 ,Phosphatidylinositol ,Nippostrongylus brasiliensis ,education ,Protein kinase A ,Protein kinase B ,Strongylida Infections ,education.field_of_study ,biology ,Helminth Proteins ,biology.organism_classification ,Rats ,Infectious Diseases ,Biochemistry ,chemistry ,Parasitology ,Nippostrongylus ,Phosphatidylinositol 3-Kinase ,Ancylostoma caninum ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Developmentally arrested infective larvae of strongylid nematodes are activated to resume growth by host-derived cues encountered during invasion of the mammalian host. Exposure of Nippostrongylus brasiliensis infective larvae to elevated temperature (37 °C) is sufficient to activate signalling pathways which result in resumption of feeding and protein secretion. This occurs independently of exposure to serum or glutathione, in contrast to the hookworm Ancylostoma caninum, and is not initiated by chemical exsheathment. No qualitative differences in protein secretion were induced by host serum as visualised by two-dimensional SDS–PAGE, although exposure of larvae to an aqueous extract of rat skin did stimulate secretion of a small pre-synthesised bolus of proteins. Infective larvae began feeding after a lag period of 3–4 h at 37 °C, reaching a maximum of 90% of the population feeding by 48 h. Neither a membrane permeant analogue of cyclic GMP nor muscarinic acetylcholine receptor agonists stimulated feeding at 20 °C, and high concentrations of both compounds inhibited temperature-induced activation. LY294002, an inhibitor of phosphatidylinositol 3-kinase, Akt inhibitor IV, an inhibitor of Akt protein kinase, and ketoconazole, an inhibitor of cytochrome P450, all blocked resumption of feeding and protein secretion at 37 °C. Serotonin increased the rate of feeding assessed by uptake of radiolabelled BSA, but could not initiate feeding independently of elevated temperature. Collectively, the data suggest that the early signalling events for larval activation in N. brasiliensis differ substantially from A. caninum, but that they may converge at pathways downstream of phosphatidylinositol 3-kinase involving steroid hormone synthesis.
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- 2010
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77. The Tumor Necrosis Factor Superfamily Member RANKL Suppresses Effector Cytokine Production in Group 3 Innate Lymphoid Cells
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Susan Gilfillan, Yasuhiro Kobayashi, Keely G. McDonald, David S.J. Allan, Stanley Ching-Cheng Huang, Marina Cella, Jennifer K. Bando, James R. Carlyle, Christina Song, Marco Colonna, and Rodney D. Newberry
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Receptors, CCR6 ,musculoskeletal diseases ,0301 basic medicine ,medicine.medical_treatment ,Immunology ,C-C chemokine receptor type 6 ,Biology ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,RAR-related orphan receptor gamma ,medicine ,Animals ,Immunology and Allergy ,Receptor ,Effector ,RANK Ligand ,Innate lymphoid cell ,Nuclear Receptor Subfamily 1, Group F, Member 3 ,Immunity, Innate ,Lymphocyte Subsets ,Cell biology ,030104 developmental biology ,Infectious Diseases ,Cytokine ,RANKL ,030220 oncology & carcinogenesis ,biology.protein ,Cytokines ,Tumor necrosis factor alpha - Abstract
While signals that activate group 3 innate lymphoid cells (ILC3s) have been described, the factors that negatively regulate these cells are less well understood. Here we found that the tumor necrosis factor (TNF) superfamily member receptor activator of nuclear factor kB ligand (RANKL) suppressed ILC3 activity in the intestine. Deletion of RANKL in ILC3s and T cells increased C-C motif chemokine receptor 6 (CCR6)+ ILC3 abundance and enhanced production of interleukin-17A (IL-17A) and IL-22 in response to IL-23 and during infection with the enteric murine pathogen Citrobacter rodentium. Additionally, CCR6+ ILC3s produced higher amounts of the master transcriptional regulator RORγt at steady state in the absence of RANKL. RANKL-mediated suppression was independent of T cells, and instead occurred via interactions between CCR6+ ILC3s that expressed both RANKL and its receptor, RANK. Thus, RANK-RANKL interactions between ILC3s regulate ILC3 abundance and activation, suggesting that cell clustering may control ILC3 activity.
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- 2018
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78. The transcription factor Bhlhe40 is a novel regulator of large peritoneal macrophages and type 2 immunity
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Nicholas N. Jarjour, Tara R. Bradstreet, Elizabeth A. Schwarzkopf, Chih-Chung Lin, Melissa E. Cook, Stanley Ching-Cheng Huang, Reshma Taneja, Gwendalyn J. Randolph, Joseph F. Urban, and Brian T. Edelson
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Immunology ,Immunology and Allergy - Abstract
Tissue-resident macrophages occupy key roles in immunity and physiology within organ microenvironments. Many tissue macrophages derive from embryonic progenitors and self-maintain locally as unique tissue-specific populations. Resident macrophages can also expand in response to type 2 stimuli including parasites and contribute to control of infection via the alternative activation program. However, the transcriptional basis for this capacity to proliferate in situ is poorly understood. We have observed that the transcription factor basic helix-loop-helix, member e40 (Bhlhe40) is highly expressed in a subset of hematopoietic cell types, including large peritoneal macrophages (LPMs). Based on this data, we hypothesized that Bhlhe40 is a key part of the LPM transcriptional network. We have found that peritoneal macrophages are selectively reduced in Bhlhe40−/− mice, in contrast to other resident macrophages. Mixed bone marrow chimeras, conditional knockout mice, and other approaches demonstrated a specific, intrinsic defect in mature, Bhlhe40-deficient LPMs. Bhlhe40−/− LPMs exhibited an alternative activation-like profile and impaired self-renewal. These functional perturbations were correlated with altered expression of gene sets pertaining to the endoplasmic reticulum (ER) and protein homeostasis, as well as ER morphology changes in Bhlhe40−/− LPMs. Using models of peritoneal type 2 immunity, we observed near-total loss of expansion of Bhlhe40-deficient LPMs, correlated with impaired control of an intestinal helminth. Our findings demonstrate critical roles for Bhlhe40 as a tissue-specific regulator of resident macrophage self-renewal and expansion during type 2 immunity.
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- 2018
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79. Synthesis and properties of various poly(diphenylacetylenes) containing tert-amine moieties
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Toshio Masuda, Ching-Cheng Huang, Masaki Maitani, Toru Katsumata, and Masashi Shiotsuki
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chemistry.chemical_classification ,Polymers and Plastics ,Trimethylsilyl ,Carbazole ,Organic Chemistry ,Polymer ,transition metal catalyst ,Triphenylamine ,chemistry.chemical_compound ,Monomer ,chemistry ,Polymerization ,Polymer chemistry ,Materials Chemistry ,Amine gas treating ,gas permeability ,substituted polyacetylene ,Diphenylacetylene - Abstract
The polymerization of diphenylacetylene derivatives possessing tert-amine moieties, such as triphenylamine, N-substituted carbazole and indole, was examined in the presence of TaCl5–n-Bu4Sn (1:2) catalyst. A polymer with high molecular weight (Mw = 570 × 103) was obtained in good yield by the polymerization of diphenylamine-containing monomer 1b, whereas the isopropylphenylamine derivative (1c) gave a polymer with relatively low molecular weight (Mw = 2.4 × 103). The polymerization of monomer 1d containing cyclohexylphenylamine group did not proceed; however, carbazolyl- and indolyl-containing monomers also produced polymers. Poly(1b), poly(2f) and poly(4b) could be fabricated into free-standing membranes by casting toluene solutions of these polymers. The gas permeability of poly(1b) was too low to be evaluated accurately whereas poly(4b) possessing two chlorine atoms in the repeating unit showed higher gas permeability than that of poly(1b); furthermore, poly(2f) having trimethylsilyl and 3-methylindolyl groups exhibited relatively high gas permeability ( P O 2 = 49 barrers ). In the cyclic voltammograms of diphenylamino group-containing polymers, poly(1b) and poly(2b), the intensities of oxidation and reduction peaks decreased more than those of carbazolyl-containing poly(2a). The molar absorptivity (ɛ) of poly(1b) at ∼700 nm increased with increasing applied voltage in the UV–vis spectrum.
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- 2008
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80. Migratory CD103+ dendritic cells suppress helminth-driven Type2 immunity through constitutive expression of IL-12
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Stanley Ching-Cheng Huang, Leentje Dreesen, Wing Y. Lam, Amber M. Smith, Christina M. O’Neill, Roxane Tussiwand, Keke C. Fairfax, Bart Everts, Kenneth M. Murphy, Edward J. Pearce, Brian T. Edelson, and Joseph F. Urban
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Liver Cirrhosis ,0301 basic medicine ,Immunology ,Helminthiasis ,Context (language use) ,chemical and pharmacologic phenomena ,Article ,Immunomodulation ,Mice ,03 medical and health sciences ,Th2 Cells ,Immune system ,Antigens, CD ,Cell Movement ,Immunity ,Helminths ,parasitic diseases ,Animals ,Immunology and Allergy ,Macrophage ,Research Articles ,Disease Resistance ,Mice, Knockout ,biology ,Toll-Like Receptors ,hemic and immune systems ,Dendritic Cells ,biology.organism_classification ,Interleukin-12 ,3. Good health ,Repressor Proteins ,Basic-Leucine Zipper Transcription Factors ,030104 developmental biology ,Gene Expression Regulation ,Immunoglobulin class switching ,Models, Animal ,Interleukin 12 ,Female ,Immunization ,Schistosoma mansoni ,Heligmosomoides polygyrus ,Integrin alpha Chains - Abstract
Everts et al. use Batf3−/− mice to examine the role of Batf3-dependent CD8α+ and CD103+ DCs in Th2 immunity in response to helminth infection. Loss of Batf3-dependent DCs resulted in rapid control of normally chronic infection with Heligmosomoides polygyrus, whereas liver fibrosis was exacerbated with Schistosoma mansoni infection. Mechanistically, steady-state IL-12 production by migratory CD103+ DCs was found to antagonize Th2 responses., CD8α+ and CD103+ dendritic cells (DCs) play a central role in the development of type 1 immune responses. However, their role in type 2 immunity remains unclear. We examined this issue using Batf3−/− mice, in which both of these DC subsets are missing. We found that Th2 cell responses, and related events such as eosinophilia, alternative macrophage activation, and immunoglobulin class switching to IgG1, were enhanced in Batf3−/− mice responding to helminth parasites. This had beneficial or detrimental consequences depending on the context. For example, Batf3 deficiency converted a normally chronic intestinal infection with Heligmosomoides polygyrus into an infection that was rapidly controlled. However, liver fibrosis, an IL-13–mediated pathological consequence of wound healing in chronic schistosomiasis, was exacerbated in Batf3−/− mice infected with Schistosoma mansoni. Mechanistically, steady-state production of IL-12 by migratory CD103+ DCs, independent of signals from commensals or TLR-initiated events, was necessary and sufficient to exert the suppressive effects on Th2 response development. These findings identify a previously unrecognized role for migratory CD103+ DCs in antagonizing type 2 immune responses.
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- 2016
81. New designed nerve conduits with a porous ionic cross-linked alginate/chitisan structure for nerve regeneration
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Jen-Ray Chaw, Hsia-Wei Liu, Yu-Chao Shih, and Ching-Cheng Huang
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Materials science ,Alginates ,Composite number ,Biomedical Engineering ,Ionic bonding ,Prosthesis Design ,Biomaterials ,Chitosan ,chemistry.chemical_compound ,Tissue engineering ,Glucuronic Acid ,Peripheral nerve ,Absorbable Implants ,Materials Testing ,Animals ,Humans ,Peripheral Nerves ,Porosity ,Ions ,Tissue Scaffolds ,Guided Tissue Regeneration ,Hexuronic Acids ,technology, industry, and agriculture ,General Medicine ,Penetration (firestop) ,equipment and supplies ,Glucuronic acid ,Nerve Regeneration ,Equipment Failure Analysis ,Cross-Linking Reagents ,chemistry ,Biomedical engineering - Abstract
A new fabrication process for designing nerve conduits with a porous ionic cross-linked alginate/chitosan composite for nervous regeneration could be prepared. New designed nerve conduits with a porous ionic cross-linked alginate/chitosan composite were developed for nervous regeneration. Nerve conduits (NCs) represent a promising alternative to conventional treatments for peripheral nerve repair. NCs composed of various polysaccharides such as sodium alginate were designed and prepared by lyophilization as potential matrices for tissue engineering. The use of a porous ionic cross-linked alginate/chitosan composite could provide penetration channels that would lead to the products' increasing penetration rate properties. Furthermore, the use of a porous ionic cross-linked alginate/chitosan composite also has a highly cross-linked structure, which would give the products relatively good mechanical properties. Furthermore, the drug could be incorporated into nerve conduits as a new drug-carrying system for nerve regeneration because of its porous and cross-linked structures.
- Published
- 2015
82. Molecular architecture effect on reactivity of polynorbornenes with pendant α,β-unsaturated amide or ester bridged chains via ring-opening metathesis polymerization
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Kueir-Rarn Lee, Ching-Cheng Huang, Juin-Yih Lai, Wen-Hsiang Chen, Shou-Mau Hong, and Der-Jang Liaw
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Materials science ,Polymers and Plastics ,Organic Chemistry ,Radical polymerization ,ROMP ,Ring-opening polymerization ,chemistry.chemical_compound ,Polymerization ,chemistry ,Amide ,Polymer chemistry ,Materials Chemistry ,Copolymer ,Ring-opening metathesis polymerisation ,Norbornene - Abstract
The molecular architecture effect on active structure of miscellaneous polynorbornenes (Scheme 1) was investigated with pendant α,β-unsaturated amide or ester groups via ring-opening metathesis polymerization (ROMP). Remarkable differences in the reactivity and polymerization behavior of active norbornenes depend on various molecular architectures. Polynorbornenes derived from active norbornenes with ethylene between urethane group and ester group such as 3a,b (Scheme 1) showed excellent solubility. Organo-insoluble precipitate was obtained after ROMP of 5c with the amide group. Random copolymerization technique of bicyclo[2.2.1]hept-2-ene (NB) and 5c with amide group was considered to be a strategy to overcome the formation of precipitates, which expected to decrease the hydrogen bonding between two amide groups. High performance polynorbornenes with active groups could be designed with high potential of application for photoresist, UV curing and elastomers. Functional poly(5b) was incorporated into poly(methyl methacylate) [poly(MMA)] to produce AB cross-linked materials. The AB cross-linked material [15 wt% poly(5b), Td10=355 °C in nitrogen] had higher thermal stability than pure poly(MMA) (Td10=250 °C in nitrogen).
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- 2006
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83. Novel fluorescent polynorbornenes with multi-functional armed structure by using highly stable block macroinitiators via a combination of living ring-opening metathesis polymerization and atom transfer radical polymerization
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En-Tang Kang, Der-Jang Liaw, and Ching-Cheng Huang
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Materials science ,Polymers and Plastics ,Atom-transfer radical-polymerization ,Organic Chemistry ,ROMP ,Metathesis ,chemistry.chemical_compound ,chemistry ,Polymerization ,Polymer chemistry ,Materials Chemistry ,Copolymer ,Ring-opening metathesis polymerisation ,Methyl methacrylate ,Norbornene - Abstract
Novel organosoluble fluorescent polynorbornenes with multi-functional armed structure were designed and prepared by using highly stable block macroinitiators via a combination of living ring-opening metathesis polymerization (ROMP) and atom transfer radical polymerization (ATRP). A bromo-containing functional norbornene (NBMBr) was prepared from the Diels–Alder reaction of cyclopentadiene and allyl bromide. The diblock copolymer of 5-( N -carbazolyl methyl)bicycle[2.2.1]hept-2-ene (CbzNB) and NBMBr was successfully prepared using living ROMP and used as a novel macroinitiator [poly(CbzNB- b -NBMBr)] for ATRP. Carbazoyl-containing multi-functional armed copolymer with poly(methyl methacrylate) (PMMA) was prepared by using poly(CbzNB- b -NBMBr) as a macroinitiator for ATRP. Strong fluorescence emissions (370–450 nm) were observed in the low excimer-forming multi-functional armed fluorescent polynorbornenes. The fact is that low excimer-forming carbazole-containing polymeric compound would apparently be favorable in photoconductive materials. The multi-functional armed structure make this compound an attractive candidate for applications as multi-modified hole transport materials in molecular electronic devices. Multi-modification could be further considered to be carried out by using such a functional bromo group at the end of multi-arms.
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- 2006
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84. Color lightness and highly organosoluble fluorinated polyamides, polyimides and poly(amide–imide)s based on noncoplanar 2,2′-dimethyl-4,4′-biphenylene units
- Author
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Ching-Cheng Huang, Wen-Hsiang Chen, and Der-Jang Liaw
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chemistry.chemical_classification ,Condensation polymer ,Materials science ,Polymers and Plastics ,Organic Chemistry ,Polymer ,Gel permeation chromatography ,chemistry.chemical_compound ,Dicarboxylic acid ,chemistry ,Diamine ,Polyamide ,Polymer chemistry ,Materials Chemistry ,Imide ,Tetrahydrofuran - Abstract
A new diamine monomer containing noncoplanar methyl substitution, 2,2′-dimethyl-4,4′-bis(2-trifluoromethyl-4-aminophenoxy)biphenyl (DBTFAPB) was successfully synthesized and used in the preparation of a series of polyamides and polyimides by direct polycondensation with various aromatic dicarboxylic acids and tertacarboxylic dianhydrides. A new noncoplanar dicarboxylic acid monomer containing noncoplanar methyl substitution, 2,2′-dimethyl-4,4′-bis(2-trifluoromethyl-4-trimellitimidophenoxy)biphenyl (DBTFTPB) was also successfully synthesized by refluxing the diamine, DBTFAPB, with trimellitic anhydride in glacial acetic acid. A series of new poly(amide–imide)s were prepared directly from DBTFTPB with various diamines in N-methyl-2-pyrrolidinone (NMP). All the polymers exhibited excellent solubility in solvents, such as N-methyl-2-pyrrolidinone (NMP), N,N-dimethylacetamide (DMAc), N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), pyridine, tetrahydrofuran (THF), cyclohexanone and γ-butyrolactone at room temperature or upon heating at 70 °C. Inherent viscosities of the polymers were found to range between 0.60 and 1.34 dL g−1. Gel permeation chromatography (GPC) of the polymers showed number-average and weight-average molecular weight up to 7.3×104 and 17.9×104, respectively. These polymers showed that the glass transition temperatures were between 230 and 265 °C, and the 10% mass loss temperatures were higher than 460 °C in nitrogen atmosphere. All the polymers could be cast into flexible and tough films from DMAc solutions. They had a tensile strength in the range of 82–124 MPa and a tensile modulus in the range of 1.9–2.9 GPa. These polymers exhibited low dielectric constants ranging from 2.87 to 4.03, low moisture absorption in the range of 0.29–3.20%, and high transparency with an ultraviolet–visible absorption cut-off wavelength in the 347–414 nm range.
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- 2006
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85. Optically Transparency and Light Color of Novel Highly Organosoluble Alicyclic Polyimides with 4-tert-Butylcyclohexyl Group
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Wen-Hsiang Chen, Ching-Cheng Huang, and Der-Jang Liaw
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chemistry.chemical_classification ,Thermogravimetric analysis ,Materials science ,Trifluoromethyl ,Polymers and Plastics ,Organic Chemistry ,Thermal decomposition ,Condensed Matter Physics ,chemistry.chemical_compound ,Alicyclic compound ,chemistry ,Diamine ,Polymer chemistry ,Materials Chemistry ,Thermal stability ,Physical and Theoretical Chemistry ,Glass transition ,Polyimide - Abstract
Novel optically transparent and highly organo-soluble alicyclic polyimides derived from bulky alicyclic diamine containing trifluoromethyl group on either side, 1,1-bis[4(2-trifluoromethyl-4aminophenoxy)phenyl]-4-tert-butylcyclohexane (BTFAPBC), were prepared. All polymers showed excellent solubility in various organic solvents like N-methyl-2-pyrrolidinone (NMP), N,N-dimethyl acetamide (DMAc), N,N-dimethyl formamide (DMF), pyridine, cyclohexanone, and γ-butyrolactone. The cut-off wavelength and 80% transmission wavelength for polyimides ranged from 362 to 407 nm and 436 to 492 nia, respectively. Polyimides with alicyclic tert-butylcyclohexyl cardo and trifluoromethyl substituents exhibited low dielectric constants ranging from 3.38 to 4.07 (at 1 KHz). Inherent viscosities of the polyimides were found to be in the range of 0.52-1.00 dL·g -1 . Polyimides showed glass transition temperatures in the range of 231-262 °C, and possessed a coefficient of thermal expansion (CTE) of 66-79 ppm.°C -1 . Thermogravimetric analyses of the polyimides revealed high thermal stability and decomposition temperature more than 450 °C in nitrogen atmosphere. The 10% weight loss temperature was found to be in the range of 453-544 and 413-502 °C in nitrogen and air atmospheres, respectively. The polyimide films had a tensile strength ranging from 84 to 100 MPa. The elongation at break varied from 6 to 12% and the tensile modulus varied from 1.1 to 2.1 GPa.
- Published
- 2006
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86. Novel organosoluble polynorbornene bearing a polar, pendant, ester-bridged epoxy group via living ring-opening metathesis polymerization
- Author
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Chun-Wei Fu, Der-Jang Liaw, and Ching-Cheng Huang
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Polymers and Plastics ,Organic Chemistry ,Dispersity ,ROMP ,chemistry.chemical_compound ,Monomer ,chemistry ,Polymerization ,Polymer chemistry ,Materials Chemistry ,Copolymer ,Living polymerization ,Ring-opening metathesis polymerisation ,Tetrahydrofuran - Abstract
A novel organosoluble polynorbornene bearing a polar, pendant, ester-bridged epoxy group [poly(oxiran-2-ylmethyl 2-methylbicyclo[2.2.1]hept-5-ene-2-carboxylate) (polyOMMC)] was prepared via the living ring-opening metathesis polymerization (ROMP) of active norbornenes with a Ru catalyst. PolyOMMC exhibited excellent solubility in a variety of solvents. The number-average molecular weight of polyOMMC linearly increased with the [M]/[I] ratio (where [M] is the monomer concentration and [I] is the initiator concentration), and a narrow polydispersity of 1.09–1.19 was observed; this was considered a living polymerization. When ROMP of oxiran-2-ylmethyl 2-methylbicyclo[2.2.1]hept-5-ene-2-carboxylate with [M]/[I] = 350 was carried out at 30 °C in CH2Cl2, the number-average molecular weight (7.01 × 104; polydispersity index = 1.07) was close to the calculated molecular weight (7.28 × 104), and a diblock copolymer was observed after the addition of another monomer ([M]/[I] = 350) with an increase in the number-average molecular weight (1.60 × 105; polydispersity index = 1.11), which was close to the calculated molecular weight (1.61 × 105). The modified polynorbornenes retained good solubility in methylene chloride, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, N,N-dimethylacetamide, and N-methyl-2-pyrrdione. High-performance polynorbornenes with active epoxy groups could be designed with great potential for applications in photoresists, UV curing, and elastomers. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4428–4434, 2006
- Published
- 2006
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87. Novel multifunctional polymeric materials with predominant cis microstructures derived from α-norbornenyl macromonomer and stable macroinitiator via ring-opening metathesis polymerization and atom transfer radical polymerization
- Author
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Der-Jang Liaw, Jing-Yang Ju, and Ching-Cheng Huang
- Subjects
Polymers and Plastics ,Atom-transfer radical-polymerization ,Chemistry ,Organic Chemistry ,Macromonomer ,Ring-opening polymerization ,End-group ,chemistry.chemical_compound ,Polymerization ,Polymer chemistry ,Materials Chemistry ,Copolymer ,Ring-opening metathesis polymerisation ,Norbornene - Abstract
Novel star-like polymeric materials with high cis content could be obtained by using α-norbornenyl macromonomers and highly stable macroinitiators derived from an active norbornene derivative [5-(2-bromo-2-methylpropionylaminomethyl)bicyclo[2.2.1]hept-2-ene (NBBrMPAM)], which was synthesized by the reaction of norbornene methylene amine and 2-bromo-2-methylpropionyl bromide. The α-norbornenyl macromonomer (NBPMMA), which is polymethyl methacrylate containing norbornenyl end group, was prepared by atom transfer radical polymerization (ATRP) using NBBrMPAM as an initiator. Star-like polynorbornene with high cis microstructure (cis/trans = 72/28) was obtained directly by ring-opening metathesis polymerization of NBPMMA macromonomer having number molecular weight (Mn) as low as 6.39 × 103. Random ring-opening metathesis copolymerization of NBPMMA and norbornene derivative containing carbazole group (NBCbz) was carried out at 25 °C by using Ru catalyst [(Cy3P)2Cl2Ru = CHPh, Cy = cyclohexyl, Ph = phenyl]. High cis (cis/trans = 63/37) organo-soluble star-like random poly(NBPMMA-co-NBCbz) was successfully obtained with high number-average molecular weight (Mn) of 4.76 × 104 and molecular weight distribution polydispersity index of 1.78. Organo-soluble comb-shaped copolymers with MMA could be successfully obtained using ATRP macroinitiator [poly(HNBBrMPAM)] in diluted macroinitiator solution with a concentration less than 3.64 × 10−2 mol.L−1. This is the first ever attempt to prepare novel star-like organo-soluble polymeric materials with high cis microstructure via the combination of ring-opening metathesis polymerization and ATRP. Multimodification could be considered to be carried out by using the functional bromo group at the end of side chains. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3382–3392, 2006
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- 2006
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88. Effects of the architecture and environment on polymeric molecular assemblies of novel amphiphilic diblock copolynorbornenes with narrow polydispersity via living ring-opening metathesis polymerization
- Author
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Der-Jang Liaw, Ching-Cheng Huang, and En-Tang Kang
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chemistry.chemical_classification ,Hydrodynamic radius ,Polymers and Plastics ,Organic Chemistry ,Dispersity ,Cationic polymerization ,Polymer ,chemistry ,Polymerization ,Polymer chemistry ,Materials Chemistry ,Copolymer ,Ring-opening metathesis polymerisation ,Thermal stability - Abstract
Diblock copolymers of 5-(methylphthalimide)bicyclo[2.2.1]hept-2-ene (NBMPI) and 1,5-cyclooctadiene were synthesized by living ring-opening metathesis polymerization with a well-defined catalyst {RuCl2(CHPh)[P(C6H11)3]2}. Unhydrogenated diblock copolymers showed two glass transitions due to poly(NBMPI) and polybutadiene segments, such as two glass-transition temperatures at −86.5 and 115.3 °C for poly1a and −87.2 and 115.3 °C for poly1b. However, only one melting temperature could be observed for hydrogenated copolymers, such as 119.8 °C for poly2a and 121.7 °C for poly2b. The unhydrogenated diblock copolymer with the longer poly(NBMPI) chain (poly1a; temperature at 10% mass loss = 400 °C) exhibited better thermal stability than the one with the shorter poly(NBMPI) chain (poly1b; temperature at 10% mass loss = 385 °C). Two kinds of hydrogenated diblock copolymers, poly2a and poly2b, exhibited relatively poor solubility but better thermal stability than unhydrogenated diblock copolymers because of the polyethylene segments. Poly[(hydrochloride quaternized 2-norbornene-5-methyleneamine)-b-butadiene]-1 (poly3a) was obtained after the hydrolysis and quaternization of poly1a. Dynamic light scattering measurements indicated that the hydrodynamic diameters of the cationic copolymer (poly3a) in water (hydrodynamic diameter = 1580 nm without salt), methanol/water (4/96 v/v; hydrodynamic diameter = 1500 nm without salt), and tetrahydrofuran/water (4/96 v/v; hydrodynamic diameter = 1200 nm without salt) decreased with increasing salt (NaCl) concentration. The effect of temperature on the hydrodynamic diameter of hydrophobically modified poly3a was also studied. The inflection point of the hydrodynamic diameter of poly3a was observed at various polymer concentrations around 30 °C. The critical micelle concentration of hydrophobically modified poly3a was observed at 0.018 g dL−1. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 2901–2911, 2006
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- 2006
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89. Novel doubly polymerizable functional norbornene: Its synthesis, reactivity, and macromolecular architectures from a dual cure via ring-opening metathesis polymerization and radical photopolymerization
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Ching-Cheng Huang, Der-Jang Liaw, and Shou-Mau Hong
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Polymers and Plastics ,Organic Chemistry ,ROMP ,Grubbs' catalyst ,chemistry.chemical_compound ,Monomer ,Photopolymer ,chemistry ,Polymerization ,Polymer chemistry ,Materials Chemistry ,Ring-opening metathesis polymerisation ,Methyl methacrylate ,Norbornene - Abstract
A novel doubly polymerizable functional norbornene, 5-(methacryloyloxyethylamino carboxylmethyl)bicyclo[2.2.1]hept-2-ene (NBMOACM), was prepared. The ring-opening metathesis polymerization (ROMP) of NBMOACM was carried out to prepare polymers with crosslinkable side chains with the Grubbs catalyst. No gel formation occurred during the ROMP of NBMOACM. The 1H NMR spectrum of poly(NBMOACM) showed broad signals between 5.10 and 5.40 ppm, corresponding to the vinyl protons of the cis and trans double bonds of the ring-opened polymer. Increasing the ratio of the monomer concentration to the catalyst concentration resulted in the formation of higher molecular weight polymers. Poly(NBMOACM) was incorporated into poly(methyl methacrylate) [poly(MMA)] to produce AB crosslinked materials. These crosslinked materials [1 wt % poly(NBMOACM), 10% weight loss temperature = 300 °C in air] had higher thermal stability than pure poly(MMA) (10% weight loss temperature = 276 °C in air). © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6287–6298, 2006
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- 2006
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90. Self-Assembly Aggregation of Highly Stable Copolynorbornenes with Amphiphilic Architecture via Ring-Opening Metathesis Polymerization
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Ching-Cheng Huang, Der-Jang Liaw, and Tsang-Pin Chen
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Aqueous solution ,Polymers and Plastics ,Chemistry ,Organic Chemistry ,Chemical modification ,Polyelectrolyte ,Inorganic Chemistry ,chemistry.chemical_compound ,Amphiphile ,Polymer chemistry ,Materials Chemistry ,Ring-opening metathesis polymerisation ,Self-assembly ,Imide ,Amphiphilic copolymer - Published
- 2005
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91. Partitioning of unsaturated hydrophilic monomer in microemulsion media monitored by pyrene fluorescence method
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Der-Jang Liaw, Ignác Capek, and Ching-Cheng Huang
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Quenching (fluorescence) ,Polymers and Plastics ,Chemistry ,Condensed Matter Physics ,Photochemistry ,Micelle ,Fluorescence spectroscopy ,Polyelectrolyte ,chemistry.chemical_compound ,Ionic strength ,Critical micelle concentration ,Micellar solutions ,Polymer chemistry ,Materials Chemistry ,Pyrene ,Physical and Theoretical Chemistry - Abstract
The extent of intra- and interchain associations of (un)charged water-soluble monomers in the homogeneous and micellar solutions was studied with steady-state fluorescence spectroscopy. Fluorescence spectroscopic experiments were performed on uncharged (acryl amide) and charged hydrophilic monomers [zwitterionic 3-dimethyl(methacryloyloxyethyl)ammonium propane sulfonate (DMAPS), etc.] with pyrene as a probe. In both the homogeneous and micellar solutions, linear Stern–Volmer plots were obtained that implied that the quenching process can be considered as totally dynamic. The Stern–Volmer constant (KSV) for DMAPS decreased with an increasing dielectric constant of solvent and the concentration of simple electrolyte. An abrupt decrease in KSV was observed in the presence of a small amount of anionic emulsifier [below the critical micelle concentration (cmc)]. The dependence of KSV on pH for DMAPS was described by a curve with a maximum at about pH = 7. This was interpreted in terms of segregation of DMAPS and the variation of a optimal microenvironment for the probe and quencher with pH. The quenching rate in the micellar solutions strongly increased above the cmc but was lower than that in the homogeneous solutions. In the micellar solutions (above the cmc), the microenvironment for an interaction between the probe and quencher was suggested to be the whole microdroplet. The dependence of KSV on pH for DMAPS is described by a curve with a maximum at about pH = 9.3. The synergistic effect arises from the segregation of charged quencher molecules within the microdroplets. The complex (or strong interaction) between quencher and additive(s) is supposed to increase the dynamic nature of microdroplets that provides an optimal microenvironment for probe and quencher. A good coemulsifier, however, removes quencher from the interface and creates a barrier for entering monomer (quencher) into the core of micelles; therefore, quenching is depressed. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 571–581, 2003
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- 2003
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92. Effect of Surfactant and Various Salts on Aqueous Solution Properties of Naphthalene-Labeled Poly(hydrochloride-quaternized 2-norbornene-5-methylamine) made by Ring-Opening Metathesis Polymerization (ROMP)
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Pi-Ling Wu, Der-Jang Liaw, and Ching-Cheng Huang
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Aqueous solution ,Polymers and Plastics ,Chemistry ,Organic Chemistry ,Cationic polymerization ,Concentration effect ,Condensed Matter Physics ,Polymerization ,Pulmonary surfactant ,Ionic strength ,Polymer chemistry ,Materials Chemistry ,Ring-opening metathesis polymerisation ,Physical and Theoretical Chemistry ,Reduced viscosity - Abstract
Naphthalene-labeled cationic poly(hydrochloride-quaternized 2-norbornene-5-methyleneamine), poly(HCQNBMA)/NA, has been prepared by ring-opening metathesis polymerization (ROMP), using {RuCl 2 (CHC 6 H 5 )-[P(C 6 H 11 ) 3 ] 2 } as a catalyst in methylene chloride, followed by hydrogenation, hydrolysis, and quaternization. The effect of salt addition on the aqueous solution properties of poly(HCQNBMA)/NA was examined in terms of reduced viscosity, surface tension and fluorescence studies. The reduced viscosity of poly(HCQNBMA)/NA is dependent on the type and concentration of salts added. The viscosity behavior of cationic poly(HCQNBMA)/NA is in contrast with polybetaines. An increase in KCl concentration causes the reduced viscosity of poly(HCQNBMA)/NA to decrease at constant poly(HCQNBMA)/NA concentration. The general shape of the surface tension versus logarithm of concentration curve for poly(HCQNBMA)/NA shows only a slow decrease with increasing polymer concentration upon addition of various salts. The surface tension increases in the series KF>KCl>KBr>KI in a given polymer concentration. When the naphthalene label was introduced into the poly(HCQNBMA), the behavior of the solution properties of the poly(HCQNBMA)/NA could be clearly defined in terms of fluorescence analysis. The quenching efficiency of NaI or CH 3 NO 2 was reduced with increasing KCl concentration arising from compacted conformation of polymer chains. A model of the interaction between poly(HCQNBMA)/NA and surfactant or salt in aqueous solution is proposed.
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- 2002
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93. Effect of salt and surfactant on aqueous solution properties of pyrene-labeled poly(3-dimethyl(methylmethacryloyl ethyl) ammonium propane sulfonate)
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Der-Jang Liaw and Ching-Cheng Huang
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chemistry.chemical_classification ,Aqueous solution ,Polymers and Plastics ,Organic Chemistry ,Concentration effect ,Salt (chemistry) ,Condensed Matter Physics ,chemistry.chemical_compound ,Sulfonate ,Pulmonary surfactant ,chemistry ,Ionic strength ,Polymer chemistry ,Materials Chemistry ,Pyrene ,Ammonium - Abstract
Photophysical and solution properties of pyrene-labeled poly(3-dimethyl(methylmethacryloyl ethyl) ammonium propane sulfonate), poly(DMAPS/Py), were studied in terms of fluorescence emission measurement. The I E /I M was shown as a function of polymer concentration in deionized water. I E /I M value decreases with an increase in the salt concentration. The addition of surfactants to the aqueous solution of poly(DMAPS/Py) can either induce the mixed micelle of intra- polymer and its surrounding surfactants and/or mixed micelle of inter-polymers and their surrounding surfactants. Models of interactions between poly(DMAPS/Py) and surfactant or divalent salt in aqueous solution are proposed.
- Published
- 2002
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94. Photophysical and aqueous solution properties of thermosensitive anionic potassium-2-sulfopropylmethacrylate/N-isopropylacrylamide/1-pyrenemethylmethacrylate terpolymer
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Tze-Shyuan Wang, Ching-Cheng Huang, and Der-Jang Liaw
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Hydrodynamic radius ,Aqueous solution ,Polymers and Plastics ,fungi ,Organic Chemistry ,Analytical chemistry ,Protonation ,Polyelectrolyte ,chemistry.chemical_compound ,Monomer ,chemistry ,Dynamic light scattering ,Pulmonary surfactant ,Polymer chemistry ,Materials Chemistry ,Pyrene - Abstract
This study describes the effect of salt on the aqueous solution property of the anionic terpolymer (SPM/NIPAM/PyMMA) of potassium-2-sulfopropylmethacrylate (SPM), N-isopropylacrylamide (NIPAM), and 1-pyrenemethylmethacrylate (PyMMA) in terms of fluorescence and dynamic light scattering. A plot of the thermally induced changes in I1/I3 and IE/IM ratios for pyrene-labeled SPM/NIPAM/PyMMA with various temperatures was showed. IE/IM value (the ratio of intensities of the excimer and the monomer fluorescence emission) of SPM/NIPAM/PyMMA, which reflects the interactions of pyrene groups and the probability of dimeric pyrene, was investigated. The ratio of intensity of the first to the third vibronic bands (I1/I3) in the fluorescence spectra of pyrene-labeled SPM/NIPAM/PyMMA depends on the polarity in the media, where pyrene exists. The IE/IM value of anionic terpolymer in aqueous solution varied with various surfactant (SDS) concentrations. Hydrodynamic diameters of anionic SPM/NIPAM/PyMMA in aqueous solution were also measured with various surfactant (SDS) concentrations. The same trends were obtained in fluorescence and dynamic light scattering measurements. At the lowered pH, the protonation of anionic terpolymer enhances hydrophobic association of polymer chains. The I1/I3 ratio decreases with increasing temperature, but the IE/IM ratio increases.
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- 2002
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95. YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells
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Cheng-Wen Wu, Ai Sheng Ho, Huan Chau Lin, Yu-Cheng Chang, Chun Chao Chang, Yi Fang Chang, Ken-Hong Lim, Chun Chia Cheng, Stanley Ching-Cheng Huang, Jungshan Chang, and Ling Huang
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0301 basic medicine ,Lung Neoplasms ,Drug Evaluation, Preclinical ,Cancer Treatment ,Gene Expression ,lcsh:Medicine ,Biochemistry ,Lung and Intrathoracic Tumors ,0302 clinical medicine ,Histocompatibility Antigens ,Medicine and Health Sciences ,Growth factor receptor inhibitor ,Epidermal growth factor receptor ,Phosphorylation ,Post-Translational Modification ,lcsh:Science ,DNA methylation ,Multidisciplinary ,biology ,Chemistry ,Autophosphorylation ,Imidazoles ,Chemical Reactions ,Chemical Synthesis ,Chromatin ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,Nucleic acids ,Oncology ,030220 oncology & carcinogenesis ,Physical Sciences ,Epigenetics ,Reductive Methylation ,DNA modification ,Chromatin modification ,Research Article ,Chromosome biology ,Homeobox protein NANOG ,Cell biology ,Antineoplastic Agents ,Afatinib ,Research and Analysis Methods ,Methylation ,03 medical and health sciences ,Cancer stem cell ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,RNA, Messenger ,Lung cancer ,A549 cell ,lcsh:R ,Cancers and Neoplasms ,Biology and Life Sciences ,Proteins ,Cancer ,Histone-Lysine N-Methyltransferase ,DNA ,medicine.disease ,030104 developmental biology ,Quinazolines ,Cancer research ,biology.protein ,lcsh:Q ,Secondary Lung Tumors ,Octamer Transcription Factor-3 ,Naphthoquinones - Abstract
Cancer stem cell survival is the leading factor for tumor recurrence after tumor-suppressive treatments. Therefore, specific and efficient inhibitors of cancer stemness must be discovered for reducing tumor recurrence. YM155 has been indicated to significantly reduce stemness-derived tumorsphere formation. However, the pharmaceutical mechanism of YM155 against cancer stemness is unclear. This study investigated the potential mechanism of YM155 against cancer stemness in lung cancer. Tumorspheres derived from epidermal growth factor receptor (EGFR)-mutant HCC827 and EGFR wild-type A549 cells expressing higher cancer stemness markers (CD133, Oct4, and Nanog) were used as cancer stemness models. We observed that EGFR autophosphorylation (Y1068) was higher in HCC827- and A549-derived tumorspheres than in parental cells; this autophosphorylation induced tumorsphere formation by activating G9a-mediated stemness. Notably, YM155 inhibited tumorsphere formation by blocking the autophosphorylation of EGFR and the EGFR-G9a-mediated stemness pathway. The chemical and genetic inhibition of EGFR and G9a revealed the significant role of the EGFR-G9a pathway in maintaining the cancer stemness property. In conclusion, this study not only revealed that EGFR could trigger tumorsphere formation by elevating G9a-mediated stemness but also demonstrated that YM155 could inhibit this formation by simultaneously blocking EGFR autophosphorylation and G9a activity, thus acting as a potent agent against lung cancer stemness.
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- 2017
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96. Carbodimide cross-linked and biodegradation-controllable small intestinal submucosa sheets
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Ching-Yi Liu, Chi-Yen Huang, Hsia-Wei Liu, and Ching-Cheng Huang
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Morphology (linguistics) ,Swine ,Biomedical Engineering ,Matrix (biology) ,Prosthesis Design ,Cell Line ,Biomaterials ,Mice ,Tissue engineering ,Cell Movement ,Tensile Strength ,Absorbable Implants ,Materials Testing ,medicine ,Cell Adhesion ,Animals ,Intestinal Mucosa ,Cell Proliferation ,Tissue Scaffolds ,Chemistry ,Cell Differentiation ,General Medicine ,Dynamic mechanical analysis ,Biodegradation ,Fibroblasts ,Small intestinal submucosa ,Equipment Failure Analysis ,Carbodiimides ,Cross-Linking Reagents ,Chemical engineering ,Collagenase ,Degradation (geology) ,Rabbits ,medicine.drug - Abstract
The small intestinal submucosa (SIS) is an acellular collagen-based matrix, primarily composed of fibrillar collagens (types I, II, and V). They enhance healing due to a minimal immune response. A good degradation rate is the degradation of materials equal to the rate of remodeling in the host. The SIS should apply a good degradation rate and cytocompatibility. In this study, a series of SIS with different degradation rates is obtained by treatment with Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). Morphology, composition, degradable ratio, mechanical properties and cytocompatibility of the SIS are evaluated. We determined a 20 μm thickness and 60 μm pore size of the native SIS. The degradable ratio of the native SIS was approximately 90% in the presence of 0.25 mg/ml collagenase for 24 hours. The storage modulus of the native SIS was 388 MPa. The degradable ratio of the SIS decreased to 6% and the storage modulus increased to 777 MPa after being treated with 30 mM EDC for 24 hours. In cytocompatibility assay, cell numbers on the native SIS were similar as on the treated SIS due to the non-toxicity of the EDC treatment process. This SIS exhibited collagenase resistance, stronger mechanical strength and good cytocompatibility after the EDC treatment concluded. The cross-linked SIS could be utilized as a potential cell carrier for tissue engineering application.
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- 2014
97. Ly6Chigh Monocytes Become Alternatively Activated Macrophages in Schistosome Granulomas with Help from CD4+ Cells
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Wing Y. Lam, Stanley Ching-Cheng Huang, Amber M. Smith, Emmanuel L. Gautier, Marcia Nascimento, Bart Everts, Gwendalyn J. Randolph, Elizabeth Bassity, and Edward J. Pearce
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Male ,Monoblast ,Pathogenesis ,Pathology and Laboratory Medicine ,Monocytes ,Hepatitis ,Mice ,White Blood Cells ,Animal Cells ,CX3CR1 ,Medicine and Health Sciences ,Macrophage ,Antigens, Ly ,Schistosomiasis ,Immune Response ,lcsh:QH301-705.5 ,Mice, Knockout ,biology ,Cell Differentiation ,Flow Cytometry ,3. Good health ,medicine.anatomical_structure ,Schistosoma mansoni ,medicine.symptom ,Cellular Types ,Research Article ,lcsh:Immunologic diseases. Allergy ,Cell type ,Immune Cells ,Immunology ,Inflammation ,Context (language use) ,Real-Time Polymerase Chain Reaction ,Microbiology ,Th2 Cells ,Virology ,Genetics ,medicine ,Animals ,Molecular Biology ,Blood Cells ,Monocyte ,Macrophages ,Immunity ,Biology and Life Sciences ,Cell Biology ,biology.organism_classification ,Acquired Immune System ,Mice, Inbred C57BL ,Disease Models, Animal ,lcsh:Biology (General) ,Immune System ,Parasitology ,lcsh:RC581-607 - Abstract
Accumulation of M2 macrophages in the liver, within the context of a strong Th2 response, is a hallmark of infection with the parasitic helminth, Schistosoma mansoni, but the origin of these cells is unclear. To explore this, we examined the relatedness of macrophages to monocytes in this setting. Our data show that both monocyte-derived and resident macrophages are engaged in the response to infection. Infection caused CCR2-dependent increases in numbers of Ly6Chi monocytes in blood and liver and of CX3CR1+ macrophages in diseased liver. Ly6Chi monocytes recovered from liver had the potential to differentiate into macrophages when cultured with M-CSF. Using pulse chase BrdU labeling, we found that most hepatic macrophages in infected mice arose from monocytes. Consistent with this, deletion of monocytes led to the loss of a subpopulation of hepatic CD11chi macrophages that was present in infected but not naïve mice. This was accompanied by a reduction in the size of egg-associated granulomas and significantly exacerbated disease. In addition to the involvement of monocytes and monocyte-derived macrophages in hepatic inflammation due to infection, we observed increased incorporation of BrdU and expression of Ki67 and MHC II in resident macrophages, indicating that these cells are participating in the response. Expression of both M2 and M1 marker genes was increased in liver from infected vs. naive mice. The M2 fingerprint in the liver was not accounted for by a single cell type, but rather reflected expression of M2 genes by various cells including macrophages, neutrophils, eosinophils and monocytes. Our data point to monocyte recruitment as the dominant process for increasing macrophage cell numbers in the liver during schistosomiasis., Author Summary Schistosomiasis is an important neglected tropical disease caused by parasitic worms of the genus Schistosoma. During infection with S. mansoni, parasite eggs become trapped in the liver and elicit granulomatous inflammation characterized by accumulations of immune cells intermixed with liver cells around the eggs. This inflammation is responsible for disease symptoms, but also plays an important role in protecting the host against liver damage that can be caused by egg products. Granulomas, by definition, contain a significant number of macrophages (phagocytic cells of the immune system). Recent work has emphasized that macrophage numbers in inflammation can increase due either to recruitment of precursor cells (called monocytes) from the blood, or as a result of proliferation of tissue-resident macrophages. Local proliferation has been noted in other worm infections, during which the immune response is Th2-like and IL-4 produced by Th2 cells promotes macrophages to become “alternatively (or M2) activated”. We examined the origin of the increased numbers of macrophages in liver inflammation due to schistosomiasis, in which there is also a prominent Th2 response. We found that the cells mostly originated from monocytes recruited into the tissue from the blood. This response was critical for host survival during infection.
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- 2014
98. Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival
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Stanley Ching-Cheng Huang, David B. Wilson, Gwendalyn J. Randolph, Genevieve Marcelin, Jeremy S. Francis, Peter L. Wang, Jesse W. Williams, Maxim N. Artyomov, Keke C. Fairfax, Paola Leone, Edward J. Pearce, Emmanuel L. Gautier, and Stoyan Ivanov
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endocrine system ,Cell Survival ,Immunology ,Molecular Sequence Data ,Enteroendocrine cell ,Apoptosis ,Cell Count ,Biology ,Amidohydrolases ,Mice ,GATA6 Transcription Factor ,Immunology and Allergy ,Animals ,Transcription factor ,Regulation of gene expression ,GATA6 ,Brief Definitive Report ,Macrophage Activation ,Cell biology ,Aspartoacylase ,Mice, Inbred C57BL ,Haematopoiesis ,Gene Expression Regulation ,Macrophages, Peritoneal ,Homeostasis - Abstract
Gata6 regulates differentiation, metabolism and survival of peritoneal macrophages., The transcription factor Gata6 regulates proliferation and differentiation of epithelial and endocrine cells and cancers. Among hematopoietic cells, Gata6 is expressed selectively in resident peritoneal macrophages. We thus examined whether the loss of Gata6 in the macrophage compartment affected peritoneal macrophages, using Lyz2-Cre x Gata6flox/flox mice to tackle this issue. In Lyz2-Cre x Gata6flox/flox mice, the resident peritoneal macrophage compartment, but not macrophages in other organs, was contracted, with only a third the normal number of macrophages remaining. Heightened rates of death explained the marked decrease in peritoneal macrophage observed. The metabolism of the remaining macrophages was skewed to favor oxidative phosphorylation and alternative activation markers were spontaneously and selectively induced in Gata6-deficient macrophages. Gene expression profiling revealed perturbed metabolic regulators, including aspartoacylase (Aspa), which facilitates generation of acetyl CoA. Mutant mice lacking functional Aspa phenocopied the higher propensity to death and led to a contraction of resident peritoneal macrophages. Thus, Gata6 regulates differentiation, metabolism, and survival of resident peritoneal macrophages.
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- 2014
99. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization
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Kelly M. Stewart, Stanley Ching-Cheng Huang, Abhishek K. Jha, Edward M. Driggers, Ekaterina Loginicheva, Karina Chmielewski, Maxim N. Artyomov, Alexey Sergushichev, Yulia Ivanova, Juliet Ashall, Bart Everts, Edward J. Pearce, and Vicky Lampropoulou
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Glycosylation ,Transcription, Genetic ,Glutamine ,Immunology ,Citric Acid Cycle ,Macrophage polarization ,Mitochondrion ,Biology ,Nitric Oxide ,Argininosuccinic Acid ,Mice ,Immunology and Allergy ,Animals ,Gene Regulatory Networks ,Aspartate Aminotransferase, Mitochondrial ,chemistry.chemical_classification ,Regulation of gene expression ,Chemokine CCL22 ,Aspartic Acid ,Uridine Diphosphate N-Acetylglucosamine ,Interleukin-6 ,Macrophages ,Immunity, Innate ,Isocitrate Dehydrogenase ,Cell biology ,Mitochondria ,Citric acid cycle ,Enzyme ,Isocitrate dehydrogenase ,Infectious Diseases ,Biochemistry ,chemistry ,Gene Expression Regulation ,Signal transduction ,Metabolic Networks and Pathways ,Signal Transduction - Abstract
SummaryMacrophage polarization involves a coordinated metabolic and transcriptional rewiring that is only partially understood. By using an integrated high-throughput transcriptional-metabolic profiling and analysis pipeline, we characterized systemic changes during murine macrophage M1 and M2 polarization. M2 polarization was found to activate glutamine catabolism and UDP-GlcNAc-associated modules. Correspondingly, glutamine deprivation or inhibition of N-glycosylation decreased M2 polarization and production of chemokine CCL22. In M1 macrophages, we identified a metabolic break at Idh, the enzyme that converts isocitrate to alpha-ketoglutarate, providing mechanistic explanation for TCA cycle fragmentation. 13C-tracer studies suggested the presence of an active variant of the aspartate-arginosuccinate shunt that compensated for this break. Consistently, inhibition of aspartate-aminotransferase, a key enzyme of the shunt, inhibited nitric oxide and interleukin-6 production in M1 macrophages, while promoting mitochondrial respiration. This systems approach provides a highly integrated picture of the physiological modules supporting macrophage polarization, identifying potential pharmacologic control points for both macrophage phenotypes.
- Published
- 2014
100. Synthesis and characterization of novel diblock copolymers of 5-(N-carbazoyl methyl)bicyclo[2.2.1]hept-2-ene and 5-(phthalimide methyl)bicyclo[2.2.1]hept-2-ene via living ring-opening metathesis polymerization
- Author
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Der-Jang Liaw, Pi-Ling Wu, and Ching-Cheng Huang
- Subjects
Materials science ,Polymers and Plastics ,Organic Chemistry ,Dispersity ,ROMP ,Phthalimide ,chemistry.chemical_compound ,Monomer ,chemistry ,Polymerization ,Polymer chemistry ,Materials Chemistry ,Copolymer ,Ring-opening metathesis polymerisation ,Thermal stability - Abstract
Ring-opening metathesis polymerization (ROMP) has been performed with {RuCl2(CHPh)[P(C6H11)3]2} catalyst to make low polydispersity block copolymers of 5-(N-carbazoyl methyl)bicyclo[2.2.1]hept-2-ene (CbzNB) and 5-(phthalimide methyl)bicyclo[2.2.1]hept-2-ene (NBMPI). Three diblock copolymers with the CbzNB and NBMPI were made, varying both molecular weight and percent of each block. The hydrogenated diblock copolymers were successfully obtained by using p-toluenesulfonylhydrazide as a reducing agent. The novel diblock copolymers were characterized by means of gel permeation chromatography (GPC) 1H NMR, fluorescence, differential scanning calorimeter (DSC) and thermogravimetric analysis (TGA). The molecular weight distributions of the diblock copolymers are narrow ( M w / M n ∼1.5). Unhydrogenated diblock copolymers exhibited a strong carbazole fluorescence, with monomer emission occurring in the near-UV at approximately 380 nm and extending into the blue–violet region. Similar results were also observed on hydrogenated diblock copolymers. All diblock copolymers exhibited good solubility in a variety of solvents such as methylene chloride, chloroform, tetrahydrofuran and 1,2-dichlorobenzene; however, there was no remarkable difference between unhydrogenated and hydrogenated diblock copolymers. Two Tg values were observed for the CbzNB segment and the NBMPI segment before and after hydrogenation. Unhydrogenated diblock copolymers exhibited good thermo-oxidative stability, losing 10% mass in the range 369–389°C in air and 400–416°C in nitrogen. However, hydrogenated diblock copolymers showed better thermal stability than unhydrogenated diblock copolymers, and 10% mass loss temperatures were recorded in the range 375–396°C in air and 415–428°C in nitrogen.
- Published
- 2001
- Full Text
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