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Hepatobiliary Transport in Health and Disease
One major function of the liver is the uptake of endo- and xenobiotics from the bloodstream and their excretion into bile. The transport systems involved in hepatobiliary transport have been recently cloned and characterized at the molecular level and it is becoming clear that mutations and polymorphisms of individual transporter molecules underlie a variety of liver diseases. Furthermore, new research has shown that bile acids, whose function in digestion is long known, also behave as signal molecules in a variety of organs, including the intestinal and biliary epithelia, sinusoidal endothelial and immune cells. This book provides indepth surveys on the structure and function of transport molecules involved in hepatobiliary transport, on the role of different bile acids receptors in various organs and their function in health and disease, the mechanisms of bile salt-induced apoptosis and hepatocyte protection, and the role of transporter mutations as causes and modifiers of liver diseases. The book will be of interest not only for biochemists, structural chemists and biologists, but also for clinicians.
Immune Escape Pathways from the HBV Core18-27 CD8 T Cell Response are Driven by Individual HLA Class I Alleles
Abstract: Background and aims: There is growing interest in T cell-based immune therapies for a functional cure of chronic HBV infection including check-point inhibition, T cell-targeted vaccines or TCR-grafted effector cells. All these approaches depend on recognition of HLA class I-presented viral peptides. The HBV core region 18-27 is an immunodominant target of CD8+ T cells and represents the prime target for T cell-based therapies. Here, a high-resolution analysis of the core18-27 specific CD8+ T cell and the selected escape pathways was performed. Methods: HLA class I typing and viral sequence analyses were performed for 464 patients with chronic HBV infection. HBV-specific CD8+ T-cell...
Cellular and Molecular Mechanisms Underlying the Pathogenesis of Hepatic Fibrosis
Worldwide, liver fibrosis is a major cause of morbidity and mortality and is associated with a high medical and economic burden. It is the common consequence of chronic liver injury due to various etiologies. During fibrogenesis, there is a progressive substitution of the liver parenchyma by scar tissue. Recent advances in the understanding of the history of liver fibrosis have shown that the pathogenesis is driven by different cell types and a large variety of soluble mediators. At present, scientists working in this field aim to increase basic knowledge, improve diagnostics, and try to translate experimental findings into new treatment modalities. This book includes 12 selected contributions from the Special Issue “Cellular and Molecular Mechanisms Underlying the Pathogenesis of Hepatic Fibrosis” that was published in Cells. These articles summarize current perspectives and findings in hepatic fibrosis research showing how scientists try to use basic scientific research to create new therapies and diagnostics.
Phase II Conjugation Enzymes and Transport Systems
This volume on conjugation enzymes and transporters serves to bring together current methods and concepts in an interesting, important and rapidly developing field of cell and systems biology. Phase II Conjugation Enzymes and Transport Systems focuses on the so-called Phase II enzymes of drug metabolism (xenobiotics), which has important ramifications for endogenous metabolism and nutrition. Also included are aspects on Phase III, transport systems. This volume of Methods in Enzymology presents current knowledge and methodology on glucuronidation, sulfation, acetylation, and transport systems in this field of research. Together with the volumes on Quinones and Quinone Enzymes (volumes 378 and 382), and on Glutathione Transferases and gamma-Glutamyl Transpeptidases (volume 401), the state of knowledge on proteomics and metabolomics of many pathways of (waste) product elimination, enzyme protein induction and gene regulation and feedback control is provided. This volume will help stimulate future investigations and speed the advance of knowledge in systems biology. A laboratory standard for more than 40 years Over 400 volumes strong Also available on ScienceDirect
Mammalian Sterols
This book provides a comprehensive description of sterols and their novel biological roles in mammalian signaling, the book covers their biosynthesis and structure, describes sterol receptor -mediated actions, their tissue distribution and their role in disease. It offers insight into new research findings, focusing specifically on novel discoveries in bile acid and oxysterol signaling, including the lanosterol-to-cholesterol intermediates. Special attention is paid on the sex distribution of these sterols (male or female) and their sexually dimorphic roles in mammalian species, such as human, rat and mouse. Since sterols and drugs (xenobiotics) use many identical receptor-mediated signaling pathways, the book will be interesting for researchers working on the cross-road of endogenous and xenobiotic metabolism, it is intended for advanced students and scientists in molecular biology and biochemistry as well as for medical doctors in hepatology.
Drug Transporters
A comprehensive guide to drug transporters that influence the absorption, distribution, and elimination of drugs in the body The development of powerful expression cloning and genome analysis techniques has facilitated the molecular identification and characterization of numerous transporters that play a crucial role in drug disposition. Explaining the principles of drug transport and the associated techniques, Drug Transporters: Molecular Characterization and Role in Drug Disposition: * Provides a comprehensive overview of drug transporters * Includes specific descriptions of transporter families, including substrate and inhibitor specificity, subcellular and tissue localization, mechanisms...
The Liver
Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries ...
Bile Acids and Their Receptors
This book focusses on the latest results related to the field of bile acids as signaling molecules and describes how these receptors have become a major pharmacological target. It covers all major areas of research in this field, from genetics, chemistry, in silico modeling, molecular biology to clinical applications, offering a cross-country view of the functional role of bile acids as signaling molecules, virtually acting on all major areas of metabolism. While FXR and GPBAR1 are essential bile acid sensors that integrate the de novo bile acid synthesis with intestinal microbiota and liver metabolism, in a broader sense, BARs play a pathogenic role in the development of common human alignments including liver, intestinal and metabolic disorders, such as steatosis (NAFLD) and steato-hepatitis (NASH), diabetes, obesity and atherosclerosis.
