This book provides a comprehensive overview of the multifaceted field of protease in the cellular environment and focuses on the recently elucidated functions of complex proteolytic systems in physiology and pathophysiology. Given the breadth and depth of information covered in the respective contributions, the book will be immensely useful for researchers working to identify targets for drug development. Multidisciplinary in scope, the book bridges the gap between fundamental and translational research, with applications in the biomedical and pharmaceutical industry, making it a thought-provoking read for basic and applied scientists engaged in biomedical research. Proteases represent one of the largest and most diverse families of enzymes known, and we now know that they are involved in every aspect of a given organism’s life functions. Under physiological conditions, proteases are regulated by their endogenous inhibitors. However, when the activity of proteases is not correctly regulated, disease processes such as tumour progression, vascular remodelling, atherosclerotic plaque progression, ulcer, rheumatoid arthritis, Alzheimer’s disease and inflammation can result. Many infective microorganisms require proteases for replication or use them as virulence factors, which has facilitated the development of protease-targeted therapies for a variety of parasitic diseases.

Researchers seeking problems that offer more hope of success often avoid subjects that seem to be difficult to approach experimentally, or subjects for which experimental results are difficult to interpret. The breakdown part of protein turnover in vivo, particularly in nervous tissue, was such a subject in the past – it was difficult to measure and difficult to explore the mechanisms involved. For factors that influence protein metabolism, it was thought that protein content, function, and distribution are controlled only by the synthetic mechanisms that can supply the needed specificity and response to stimuli. The role of breakdown was thought to be only a general metabolic digestion, elimination of excess polypeptides. We now know that the role of breakdown is much more complex: it has multiple functions, it is coupled to turnover, and it can affect protein composition, function, and synthesis. In addition to eliminating abnormal proteins, breakdown has many modulatory functions: it serves to activate and inactivate enzymes, modulate membrane function, alter receptor channel properties, affect transcription and cell cycle, form active peptides, and much more. The hydrolysis of peptide bonds often involves multiple steps, many enzymes, and cycles (such as ubiquination), and often requires the activity of enzyme complexes. Their activation, modification, and inactivation can thus play an important role in biological functions, with numerous families of proteases participating. The specific role of each remains to be elucidated.

Proteases are everywhere from prokaryotes to eukaryotes, from virus to bacteria and in all human tissues, playing a role in many biological functions. Among these functions, the inflammatory reaction is of particular interest. In inflamed tissues, proteases can have a microbial and/or host origin and are involved not only in tissue remodeling, but also in specific signaling to resident or inflammatory cells, thereby contributing to the innate immune response. This volume presents all advances in our knowledge of the role proteases and their inhibitors play in various diseases associated with inflammatory response. Mechanisms involved in protease signaling to cells are presented, and the different types of proteases that are present at inflammatory sites and their effects on the course of inflammation are discussed. Finally, the evidence for considering proteases and their receptors as potential molecular targets for therapeutic interventions in the treatment of inflammatory diseases is discussed in the context of specific organ inflammatory pathologies (the lung, gastrointestinal tract, skin, joints, etc.).

In recent years, there has been increased research on cellular pathophysiology in animal and tissue models simulating human disease processes. The result of this research, which has been carried out primarily by physiologists, pharmacologists, biochemists, anatomists, pathologists, and clinicians, is now presented in this forum. A better understanding of how cellular, subcellular and molecular mechanisms initiate and progressively intensify organic/systemic disease processes is important in the development of rational therapies against these disease processes.

Learn the what, how, and why of pathophysiology! With easy-to-read, in-depth descriptions of disease, disease etiology, and disease processes, Pathophysiology: The Biologic Basis for Disease in Adults and Children, 8th Edition helps you understand the most important and most complex pathophysiology concepts. This updated text includes more than 1,300 full-color illustrations and photographs to make it easier to identify normal anatomy and physiology, as well as alterations of function. This edition includes a NEW chapter on obesity and nutritional disorders, along with expanded coverage of rare diseases and epigenetics. It's the most comprehensive and authoritative pathophysiology text available! - The most comprehensive and authoritative pathophysiology text on the market provides unparalleled coverage of Pathophysiology content. - Over 1,300 full-color illustrations and photographs depict the clinical manifestations of disease and disease processes — more than in any other pathophysiology text. - Consistent presentation of diseases includes pathophysiology, clinical manifestations, and evaluation and treatment. - Lifespan content includes ten separate pediatric chapters and special sections with aging and pediatrics content. - Outstanding authors Kathryn McCance and Sue Huether have extensive backgrounds as researchers and instructors, and utilize expert contributors, consultants, and reviewers in developing this edition. - Algorithms and flowcharts of diseases and disorders make it easy for you to follow the sequential progression of disease processes. - Additional What's New boxes highlight the most current research and clinical development. - Nutrition and Disease boxes explain the link between concepts of health promotion and disease. - Chapter summary reviews provide concise synopses of the main points of each chapter. - NEW! Chapter on obesity and nutritional disorders thoroughly covers these growing global concerns. - NEW! Added coverage of rare diseases and epigenetics further explore genetic disease traits. - NEW! Over 50 new or heavily revised illustrations visually highlight pathophysiology concepts. - NEW! More than 30 new 3D animations on Evolve bring difficult concepts to life for a new perspective on disease processes.

Volume I.A An outbreak of a respiratory disease first reported in Wuhan, China in December 2019 and the causative agent was discovered in January 2020 to be a novel betacoronovirus of the same subgenus as SARS-CoV and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus disease 2019 (COVID-19) has rapidly disseminated worldwide, with clinical manifestations ranging from mild respiratory symptoms to severe pneumonia and a fatality rate estimated around 2%. Person to person transmission is occurring both in the community and healthcare settings. The World Health Organization (WHO) has recently declared the COVID-19 epidemic a public health emergency of international concern. The ongoing outbreak presents many clinical and public health management challenges due to limited understanding of viral pathogenesis, risk factors for infection, natural history of disease including clinical presentation and outcomes, prognostic factors for severe illness, period of infectivity, modes and extent of virus inter-human transmission, as well as effective preventive measures and public health response and containment interventions. There are no antiviral treatment nor vaccine available but fast track research and development efforts including clinical therapeutic trials are ongoing across the world. Managing this serious epidemic requires the appropriate deployment of limited human resources across all cadres of health care and public health staff, including clinical, laboratory, managerial and epidemiological data analysis and risk assessment experts. It presents challenges around public communication and messaging around risk, with the potential for misinformation and disinformation. Therefore, integrated operational research and intervention, learning from experiences across different fields and settings should contribute towards better understanding and managing COVID-19. This Research Topic aims to highlight interdisciplinary research approaches deployed during the COVID-19 epidemic, addressing knowledge gaps and generating evidence for its improved management and control. It will incorporate critical, theoretically informed and empirically grounded original research contributions using diverse approaches, experimental, observational and intervention studies, conceptual framing, expert opinions and reviews from across the world. The Research Topic proposes a multi-dimensional approach to improving the management of COVID-19 with scientific contributions from all areas of virology, immunology, clinical microbiology, epidemiology, therapeutics, communications as well as infection prevention and public health risk assessment and management studies.

With easy-to-read, in-depth descriptions of disease, disease etiology, and disease processes, Pathophysiology: The Biologic Basis for Disease in Adults and Children, 7th Edition helps you understand the most important and the most complex pathophysiology concepts. More than 1,200 full-color illustrations and photographs make it easier to identify normal anatomy and physiology, as well as alterations of function. This edition includes a NEW Epigenetics and Disease chapter along with additional What's New boxes highlighting the latest advances in pathophysiology. Written by well-known educators Kathryn McCance and Sue Huether, and joined by a team of expert contributors, this resource is the most comprehensive and authoritative pathophysiology text available! Over 1,200 full-color illustrations and photographs depict the clinical manifestations of disease and disease processes - more than in any other pathophysiology text. A fully updated glossary includes 1,000 terms, and makes lookup easier by grouping together similar topics and terms. Outstanding authors Kathryn McCance and Sue Huether have extensive backgrounds as researchers and instructors, and utilize expert contributors, consultants, and reviewers in developing this edition. Chapter summary reviews provide concise synopses of the main points of each chapter. Consistent presentation of diseases includes pathophysiology, clinical manifestations, and evaluation and treatment. Lifespan content includes ten separate pediatric chapters and special sections with aging and pediatrics content. Algorithms and flowcharts of diseases and disorders make it easy to follow the sequential progression of disease processes. Nutrition and Disease boxes explain the link between concepts of health promotion and disease. EXTENSIVELY Updated content reflects advances in pathophysiology including tumor biology invasion and metastases, the epidemiology of cancer, diabetes mellitus, insulin resistance, thyroid and adrenal gland disorders, female reproductive disorders including benign breast diseases and breast cancer, and a separate chapter on male reproductive disorders and cancer. NEW! Chapter on epigenetics and disease. Additional What's New boxes highlight the most current research and clinical development.