Innovative Medicine : Basic Research and Development.
| Main Author: | |
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| Other Authors: | , |
| Format: | eBook |
| Language: | English |
| Published: |
Tokyo :
Springer Japan,
2015.
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| Edition: | 1st ed. |
| Subjects: | |
| Online Access: | Click to View |
Table of Contents:
- Intro
- Preface
- Contents
- Part I: Basic Research for Innovative Medicine
- Diverting Glycolysis to Combat Oxidative Stress
- Chemical Definition and Sources of ROS
- Physiology of ROS
- Biochemical Mechanisms that Preserve Redox Homeostasis
- Metabolic Adaptations to ROS
- The Pentose Phosphate Pathway and NADPH Production
- Phosphofructokinase-1 Inhibition
- Glyceraldehyde 3-Phosphate Dehydrogenase Inhibition
- Pyruvate Kinase M2 Inhibition
- De Novo Serine Synthesis
- Conclusion
- References
- Metabolic Regulation by Nuclear Receptors
- Introduction
- NR Endogenous Ligands Are Dietary Sensors
- Gut and Gut Microbiota
- De Novo Lipogenesis
- Integrative Physiology-Nuclear Receptor-Mediated Crosstalk
- Fibroblast Growth Factors
- Lipids
- Concluding Remarks
- References
- Fighting Fire with Fire in Cancer
- Introduction
- Boosting the Immune System
- Targeting CTLA-4
- IL-7 Treatment
- Targeting Cancer Cell Metabolism
- Targeting Carnitine Palmitoyltransferase-1C
- Targeting Mutated Isocitrate Dehydrogenases
- Targeting Reactive Oxygen Species
- Exploiting Cancer Cell Aneuploidy
- Conclusion
- References
- Linear Polyubiquitination: A Crucial Regulator of NF-κB Activation
- The Ubiquitin Conjugation System
- The Canonical NF-κB Activation Pathways
- The Linear Ubiquitin Chains and Their Roles in NF-κB Activation
- Mechanism Underlying Linear Ubiquitin Chain-Mediated NF-κB Activation
- Perspectives
- References
- VCP, a Major ATPase in the Cells, as a Novel Drug Target for Currently Incurable Disorders
- Background
- VCP in Neurodegenerative Disorders
- Development of Novel Inhibitors (KUSs) of VCP ATPase Activity That Do Not Block VCP Cellular Functions
- KUSs Protected Cells Under ER Stress-Inducing Conditions
- KUSs or Exogenous ATP Prevented ER Stress in Cultured Cells.
- KUSs Mitigated Pathologies of rd10, a Mouse Model of Retinitis Pigmentosa
- Discussion
- References
- Roles of E-cadherin in Hepatocarcinogenesis
- Introduction
- Results
- Physiological Function of E-cadherin in the Liver
- Progenitor Cell Proliferation in CDH1ΔL Mice
- Loss of E-cadherin Accelerates Oncogene-Addicted Liver Carcinogenesis
- Loss of E-cadherin Promotes Chemical-Induced HCC
- Relationship Between E-cadherin Loss and Mesenchymal and Stem Cell Markers in Human HCC
- Discussion
- References
- The Hippo Signaling Pathway: A Candidate New Drug Target for Malignant Tumors
- Introduction
- Loss of Hippo Signaling in the Liver
- Loss of Hippo Signaling in the Pancreas
- Loss of Hippo Signaling in the Intestine
- Loss of Hippo Signaling in the Lung
- Loss of Hippo Signaling in the Skin
- Loss of Hippo Signaling in T Lymphocytes
- Loss of Hippo Signaling in Salivary Glands
- Loss of Hippo Signaling in Neurons
- Loss of Hippo Signaling in Bone
- Concluding Remarks
- References
- Inhibitory Immunoreceptors on Mast Cells in Allergy and Inflammation
- Introduction
- Allergin-1
- Identification of Allergin-1
- Expression of Allergin-1
- Function of Allergin-1
- In Vitro Analyses of Allergin-1
- In Vivo Analyses of Allergin-1
- CD300a
- Identification and Expression of CD300a
- Identification of a Ligand for CD300a
- Function of CD300a
- In Vitro Analyses of CD300a
- In Vivo Analyses of CD300a
- Blockade of CD300a-PS Interaction Prolonged Survival of Mice After CLP
- Conclusion
- References
- Doxycycline-Inducible Autoimmune Blistering Skin Disease Model
- Bullous Pemphigoid (BP), The Most Common Autoimmune Blistering Disease
- Clinical Features of BP
- Pathogenesis of BP
- COL17 as a Main AutoAg for BP
- BP Models Produced by "Humanization of Autoantigen"
- Generation of COL17-Humanized Mice.
- Neonatal BP Model Induced by Maternally Transferred Abs to Human COL17
- Active BP Model
- Doxycycline-Inducible BP Model
- Perspectives
- References
- T Cell Senescence and Autoimmunity
- Introduction: Immune Aging and Senescence- Associated T Cells
- SA-T Cells Represent an Endogenously Arising Follicular T Cell Population with Age
- SA-T Cells Increase Robustly in Bone Fide Lupus-Prone Mice
- SA-T Cells Show Typical Signs and Features of Cellular Senescence
- SA-T Cells Are Activated in Response to Autologous GC B Cells to Produce OPN that Protects Against B Cell Apoptosis in GCs
- Involvement of SA-T Cells in the Expansion of GCs and Autoimmunity in Lupus
- Conclusion and Perspectives
- References
- Part II: Translational Research for Innovative Medicine
- IL-6: A New Era for the Treatment of Autoimmune Inflammatory Diseases
- Introduction
- Pleiotropic Function of IL-6
- Effect of IL-6 in Immune Response
- Effect of IL-6 in Acute-Phase Response
- Other Effects of IL-6
- IL-6 Signaling Systems
- Regulatory Mechanisms of IL-6 Synthesis
- Transcriptional and Post-transcriptional Regulation of IL-6
- Pathological Role of IL-6 in Autoimmune Inflammatory Diseases
- IL-6-Targeting Strategies: A New Era for the Treatment of Autoimmune Inflammatory Diseases
- Efficacy of Tocilizumab in Rheumatoid Arthritis
- Efficacy of Tocilizumab in Systemic Juvenile Idiopathic Arthritis
- Efficacy of Tocilizumab in Castleman's Disease
- Efficacy of Tocilizumab in Other Autoimmune Inflammatory Diseases
- Mechanisms Through Which Tocilizumab Is Efficacious in Various Autoimmune Inflammatory Diseases
- Concluding Remarks
- References
- Pathogenesis of Non-alcoholic Steatohepatitis and Its Potential Therapeutic Strategies
- Introduction
- Interaction Between Adipocytes and Macrophages in Obese Adipose Tissue.
- Development of a Novel Rodent Model of NASH
- Identification of Hepatic Crown-Like Structure (hCLS)
- Macrophage-Induced C-Type Lectin (Mincle)
- Role of Mincle in Adipose Tissue Remodeling and Ectopic Fat Accumulation
- Summary
- References
- Multifaceted Translational Approach to Major Mental Illness
- Introduction
- Major Mental Illness Caused by a Combination of Multiple Genetic Risk Factors and Environmental Stressors in the Pathological Trajectory
- Research Infrastructure That Allows a Multifaceted Translational Approach to Major Mental Illness
- Two Representative Studies that Use the Research Infrastructure
- References
- Translational Research of Leptin in Lipodystrophy and Its Related Diseases
- Introduction
- Transgenic Mice Overexpressing Leptin
- Crossbreeding Experiment of LepTg Mice with A-ZIPTg Mice
- Leptin Replacement Therapy in Japanese Patients with Lipodystrophy
- Significance of Hepatic AMPK in the Metabolic Action of Leptin
- fMRI Analysis of Food-Related Brain Activity in Patients with Lipodystrophy
- Conclusions
- References
- Translational Research of the Activation of the C-Type Natriuretic Peptide (CNP)-Guanylyl Cyclase-B Pathway for Skeletal Dysplasia
- Introduction
- Skeletal Phenotypes of the CNP/GC-B System in Genetically Engineered Mice
- Importance of CNP/GC-B Signaling in Endochondral Bone Growth in Humans: Lessons from Rare Congenital Skeletal Disorders
- Translational Research into Activation of CNP/GC-B Signaling for Skeletal Dysplasias
- Conclusions and Future Prospects
- References
- Clarity and Challenges in Tissue Fibrosis
- Introduction
- Liver Fibrosis
- Mechanisms
- Role of Autophagy
- Genetic Models of Liver Fibrosis
- Reversibility of Hepatic Fibrosis
- Genomics of Fibrosis
- Framework for Antifibrotic Therapies
- Summary
- References.
- TRP Channels: Their Function and Potentiality as Drug Targets
- Introduction
- Modulation of Trpa1 Channel Activity
- Oxidation Sensitivity of the Trpa1 Channel
- Modulation of Trpa1 by Other Activators and Inhibitors
- Subtype-Selective S-Nitrosylation by a Novel Nitrosamine
- TRPC Channels as Therapeutic Targets for Heart Failure
- Structure and Function of TRPC Channels
- Role of TRPC Channels in Pathological Cardiac Remodeling
- Negative Feedback Mechanism in TRPC Channels
- Suppression of Pathological Cardiac Hypertrophy by TRPC3/6 Inhibition
- Conclusion
- References
- Autophagic Cell Death and Cancer Chemotherapeutics
- Apoptosis and Other Types of Cell Death
- Autophagy
- Alternative Macroautophagy
- Autophagic Cell Death
- Cancer and Autophagic Cell Death
- Autophagic Cell Death and Cancer Chemotherapeutics
- References
- Adrenomedullin as a Potential Therapeutic Agent for Refractory Ulcerative Colitis
- Introduction
- Basic Characteristics of AM
- Pathophysiological Roles of AM in Inflammation
- Preclinical Pharmacological Effect of AM in Experimental Model of Colitis
- Exploratory Clinical Study of AM as a Therapeutic Agent for Refractory Ulcerative Colitis
- Conclusion
- References
- RNA Activation
- Introduction
- Molecular Mechanism
- saRNA-Associated Proteins
- Argonaute Proteins
- Heterogeneous Nuclear RNA-Binding Proteins
- Histone Modification Enzymes
- Target Site Selection of saRNA
- Application of saRNA
- Stem Cell Differentiation
- Clinical Therapy (Regenerative Medicine)
- Concluding Remarks
- References
- Part III: New Technology for Innovative Medicine
- Proceedings of the Uehara Memorial Foundation. Innovative Medicine: Basic Research and Development. Cardiac Reprogramming for Heart Repair
- Introduction
- Cell Fate Conversion by Transcription Factors.
- Direct Reprogramming of Mouse Fibroblasts into Cardiomyocytes in Vitro.