Repression Of Hnf4a Enables Transcriptomic Reprogramming During The Hepatic Acute Phase Response

The hepatic acute-phase response is characterized by a massive upregulation of serum proteins, such as haptoglobin and serum amyloid A, at the expense of liver homeostatic functions. Although the transcription factor hepatocyte nuclear factor 4 alpha (HNF4A) has a well-established role in safeguarding liver function and its cistrome spans around 50% of liver-specific genes, its role in the acute-phase response has received little attention so far. We demonstrate that HNF4A binds to and represses acute-phase genes under basal conditions. The reprogramming of hepatic transcription during inflammation necessitates loss of HNF4A function to allow expression of acute-phase genes while liver homeostatic genes are repressed. In a pre-clinical liver organoid model overexpression of HNF4A maintained liver functionality in spite of inflammation-induced cell damage. Conversely, HNF4A overexpression potently impaired the acute-phase response by retaining chromatin at regulatory regions of acute-phase genes inaccessible to transcription. Taken together, our data extend the understanding of dual HNF4A action as transcriptional activator and repressor, establishing HNF4A as gatekeeper for the hepatic acute-phase response.

Completely revised new edition of the premier reference on pediatric liver disease. Liver Disease in Children, 3rd Edition provides authoritative coverage of every aspect of liver disease affecting infants, children, and adolescents. The book offers an integrated approach to the science and clinical practice of pediatric hepatology and charts the substantial progress in understanding and treating these diseases. Chapters are written by international experts and address the unique pathophysiology, manifestations, and management of these disorders in the pediatric population. The third edition has been thoroughly updated and features new contributions on liver development, cholestatic and autoimmune disorders, fatty liver disease, and inborn errors of metabolism. With the continued evolution of pediatric hepatology as a discipline, this text remains an essential reference for all physicians involved in the care of children with liver disease.

This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.

In 1890 a case of myxedema was treated in Lisbon by the implantation of a sheep thyroid gland with the immediate improvement in the patient’s condition. A few years later, medications for the then ill-explained condition of the menopause included tablets made from cow ovaries. In the first quarter of the 20th century the identification of vitamin D, and its sunlight driven production in skin, paved the way to the elimination of rickets as a major medical problem. Twenty years or so later, Sir Vincent Wigglesworth established the endocrine basis of developmental moulting in insects, arguably the most commonly performed animal behaviour on Planet Earth. A paradigm that would unify these disparate observations arose between 1985 and 1987 beginning with the identification of the glucocorticoid receptor and the nuclear receptor super-family. What follows is a timely and positive manifestation of the capacity, productivity and value of international human scientific endeavour. Based on intrigue, lively competition and cooperation a global effort has rapidly fostered a school of biology with widespread ramifications for the understanding of metazoan animals, the human condition and the state of the planet. This book is the first this century to try and capture the spirit of this endeavour, to depict where the field is now and to identify some of the challenges and opportunities for the future.

Experts from academia, the biotechnology and pharmaceutical industries introduce biological, medical and methodological aspects of the emerging field of epigenomics.

Recent studies have highlighted that epithelial-mesenchymal transition (EMT) is not only about cell migration and invasion, but it can also govern many other important elements such as immunosuppression, metabolic reprogramming, senescence-associated secretory phenotype (SASP), stem cell properties, therapy resistance, and tumor microenvironment interactions. With the on-going debate about the requirement of EMT for cancer metastasis, an emerging focus on intermediate states of EMT and its reverse process mesenchymal-epithelial transition (MET) offer new ideas for metastatic requirements and the dynamics of EMT/MET during the entire metastatic cascade. Therefore, we would like to initiate discussions on viewing EMT and its downstream signaling networks as a fulcrum of cellular plasticity, and a facilitator of the adaptive responses of cancer cells to distant organ microenvironments and various therapeutic assaults. We hereby invite scientists who have prominently contributed to this field, and whose valuable insights have led to the appreciation of epithelial-mesenchymal plasticity as a more comprehensive mediator of the adaptive response of cancer cells, with huge implications in metastasis, drug resistance, tumor relapse, and patient survival.

This book explores in depth a wide range of new biomaterials that hold great promise for applications in regenerative medicine. The opening two sections are devoted to biomaterials designed to direct stem cell fate and regulate signaling pathways. Diverse novel functional biomaterials, including injectable nanocomposite hydrogels, electrosprayed nanoparticles, and waterborne polyurethane-based materials, are then discussed. The fourth section focuses on inorganic biomaterials, such as nanobioceramics, hydroxyapatite, and titanium dioxide. Finally, up-to-date information is provided on a wide range of smart natural biomaterials, ranging from silk fibroin-based scaffolds and collagen type I to chitosan, mussel-inspired biomaterials, and natural polymeric scaffolds. This is one of two books to be based on contributions from leading experts that were delivered at the 2018 Asia University Symposium on Biomedical Engineering in Seoul, Korea – the companion book examines in depth the latest enabling technologies for regenerative medicine.

This volume presents one of the clinical foundations of vasculopathies: the biological markers and risk factors associated with cardiovascular disease. A detailed biological and clinical framework is provided as a prerequisite for adequate modeling. Chapter 1 presents cardiovascular risk factors and markers, where the search for new criteria is aimed at improving early detection of chronic diseases. The subsequent chapters focus on hypertension, which involves the kidney among other organs as well as many agents, hyperglycemia and diabetes, hyperlipidemias and obesity, and behavior. The last of these risk factors includes altered circadian rhythm, tobacco and alcohol consumption, physical inactivity, and diet. The volumes in this series present all of the data needed at various length scales for a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. The cardiovascular and respiratory systems are tightly coupled, as their primary function is to supply oxygen to and remove carbon dioxide from the body's cells. Because physiological conduits have deformable and reactive walls, macroscopic flow behavior and prediction must be coupled to nano- and microscopic events in a corrector scheme of regulated mechanisms. Therefore, investigation of flows of blood and air in anatomical conduits requires an understanding of the biology, chemistry, and physics of these systems together with the mathematical tools to describe their functioning in quantitative terms.