The inflammasome is a protein complex composed of an intracellular sensor—typically a Nod-like receptor (NLR), the precursor procaspase-1, and the adaptor ASC. Inflammasome activation leads to the maturation of caspase-1 and the processing of its substrates, IL-1β and IL-18. The inflammasome has been implicated numerous diseases, and blockade of inflammasome-derived IL-1β has beneficial effects on several of these diseases. Different books have been edited about the biology of inflammasomes and about methods to study, however, the implication of this complex in the different diseases and pathological conditions show the need of a book about the clinical implications and therapeutic options. This project will show the context where inflammasomes are being studied and the molecular implications in the medical and clinical contexts. Other important topic of the inflammasomes will be the development of pharmacological inhibitors in order to improve new clinical applications. In this sense, we can find new drugs with inhibitory effects or old drugs with an inhibitory potential effect. There is a need for re-establishing the real benefits of the inflammasome inhibitions in pathological situations and the management of the differents diseases where inflammasomes are implicated.
This Methods in Molecular Biology book offers methods for studying inflammasome function, including generation of inflammasome stimuli, monitoring of caspase-1 activity and processing, activation of IL-1β cytokines, plus lab protocols, material lists and tips.
Diabetic cardiomyopathy is a clinical condition of heart dysfunction that develops in the absence of hypertension and coronary atherosclerosis in diabetic patients. The main characteristics of diabetic cardiomyopathy are myocardial fibrosis, cardiac stiffness, left ventricular hypertrophy and decreased left ventricular compliance. This eventually progresses to clinical heart failure with reduced ejection fraction. To detect changes in cardiac structure and function, such as fibrosis, several noninvasive techniques have been used. These include echocardiography, cinematic magnetic resonance imaging, and computed tomography. From a mechanistic perspective; oxidative stress, inflammation, enhanced production and deposition of advanced glycation end products (AGEs), mitochondrial dysfunction, impaired mitochondrial Ca2+ handling and function, and endoplasmic reticulum stress are observed. Furthermore activation of the sympathetic nervous system and renin-angiotensin system, microvascular dysfunction, and cardiac metabolic disorders are involved in the pathophysiology of this condition. Numerous proteins and signaling pathways, such as AMPK, FOXO1, SERCA2A, NF-kB, Nrf2, HO-1, MAPK, PKC, and PPARs, may be implicated in the development of diabetic cardiomyopathy. Additionally, increased levels of O-linked N-acetylglucosamine (O-GlcNAc), C-reactive protein, atrial natriuretic peptide, and, brain natriuretic peptide, among others, may also serve as clinical biomarkers to identify diabetic cardiomyopathy. Lifestyle modifications including aerobic exercise, maintaining a healthy weight, and smoking cessation are beneficial treatment measures to avoid diabetic cardiomyopathy. It is significant to note that in people with diabetes mellitus; high blood glucose and systemic and cardiac insulin resistance, are independently correlated to the development and progression of cardiac dysfunction and heart failure. The prevalence of diabetic cardiomyopathy declines with sustained glycemic management. However, a formal definition for diabetic cardiomyopathy as a distinct clinical entity remains poorly defined due to a lack of accepted diagnostic criteria and knowledge of subclinical cardiovascular diseases at the early stages of diabetes mellitus. There is currently no distinct histological features, biochemical markers, or clinical manifestation that can be used to make a definitive diagnosis of diabetic cardiomyopathy. Additionally, there are no prospective clinical trials to back up the claim that high insulin or blood sugar levels alone, without additional risk factors like obesity, coronary heart disease, or high blood pressure, increase the likelihood of developing diabetic cardiomyopathy. To decipher the precise mechanisms behind the onset and progression of diabetic cardiomyopathy, and to develop novel strategies for reducing the risk of heart failure in people with diabetes, further research is necessary. Hence, more clinical observational studies are required to comprehend the unknown factors underlying diabetic cardiomyopathy, and to further investigate novel biomarkers that can be used for risk assessment, screening, and diagnosis. Early detection and early intervention are essential for preventing diabetic cardiomyopathy, which drives ongoing research to better understand and treat this condition.
Life-threatening organ dysfunction/failure in critically ill patients suffering from sepsis or trauma is caused by a dysregulated host response to infection and/or inflammation. Despite significant advances in our understanding of some of the key signaling pathways involved in the excessive inflammation associated with sepsis/trauma, the translation of our current understanding of the underlying pathophysiology into organ-protective therapeutic strategies is still very limited. Current therapeutic approaches, hence, continue to rely on source control, antibiotics and supportive care, and particularly early goal-directed therapy.
Inflammation and Immunity in Depression: Basic Science and Clinical Applications is the first book to move beyond the established theory of cytokine-induced depression and explore the broader role the immune system plays in this devastating mood disorder. The book fully explores the most recent lines of research into this rapidly advancing field, including alterations of T-cells, the neurobiological implications of neuroinflammation and immune alterations for brain development and function, and the genetic components of neuroinflammation in depression, including the relationships between stress and inflammation that are revealing gene-environment interactions in the disorder. Combining contributions from researchers worldwide, this book provides the most comprehensive discussion available today on the involvement of the innate immune and adaptive immune systems in depressive disorder. Chapters span neuroscience, psychology, clinical applications and future directions, making this book an invaluable resource for advanced students, researchers and practitioners who need to understand the complex and varied role of inflammation and immune responses in depression. - Synthesizes current knowledge of inflammation and immunity in depression, ranging from basic neuroscience research, to clinical applications in psychiatry - Expands on the long-established theory of cytokine-induced depression to discuss broader involvement of the immune system - Explores translational potential of targeting immune dysfunction for clinical interventions
As the number of patients with colitis-associated cancer (CAC) is on the increase, the purpose of this book is to review the latest topics concerning management of the disease. In recent years, the diagnostic power of endoscopy and molecular pathology has also grown tremendously, as a result of which they now have a far greater influence on the treatment of CAC. At the moment, appropriate monitoring programs for ulcerative colitis and Crohn’s disease remain uncertain. At the same time, the latest findings on DNA methylation and microRNAs hold the promise of making revolutionary changes in these areas. Moreover, recent drug advances in the treatment of inflammatory bowel diseases have changed surgical indications. On the other hand, the indication of mucosectomy on colorectal cancer in ulcerative colitis and prophylactic abdominoperineal resection for Crohn’s disease remain controversial. This book provides the latest information on the remaining issues of CAC from the point of view of expert surgeons.
Dieses Fachbuch erläutert die molekularen Grundlagen von Entzündungen, spannt den Bogen zu Infektionskrankheiten und den Zusammenhang zwischen Entzündungen und chronischen Erkrankungen, behandelt abschließend den Heilungsprozess und zeigt Therapiemöglichkeiten.
Inflammasome Biology: Fundamentals, Role in Disease States, and Therapeutic Opportunities is a complete reference on the role of inflammasomes in health and disease. Sections cover the different types of inflammasomes, including cellular signaling, structural and evolutive aspects, overview the role of inflammasomes in key diseases, microbial infections and human body systems conditions, cover the interplay between Inflammasomes and cell death processes, and discuss current therapeutic opportunities driven by inflammasome research, including targeting, blocking and inhibiting the development of inflammasomes through both synthetic and natural compounds. This book is the perfect reference for cell biologists, immunologists and research clinicians to understand the foundations of inflammasomes and explore the therapeutic opportunities they present. Pharma researchers may also find this reference invaluable in devising new approaches to developing anti-inflammatory drugs. - Provides comprehensive coverage of the subject of inflammasome biology - Authored by leading experts worldwide - Provides biological insights that have both health implications and therapeutic potential
This authoritative handbook covers all aspects of immunosenescence, with contributions from experts in the research and clinical areas. It examines methods and models for studying immunosenescence; genetics; mechanisms including receptors and signal transduction; clinical relevance in disease states including infections, autoimmunity, cancer, metabolic syndrome, neurodegenerative diseases, frailty and osteoporosis; and much more.
Inflammation triggers specific metabolic pathways and if not resolved, translates into several painful diseases such as rheumatoid arthritis, lupus, Alzheimer's disease, cardiovascular disorders and psoriasis. Various processes have been explored to understand the factors behind inflammation and consequently, many mechanisms have been examined to suppress it. The nucleotide-binding domain like receptor 3 (NLRP3) inflammasome is an example of such factors which is responsible for triggering sterile and microbe induced inflammation. Studies of genetic variants of the related gene have revealed insights into the mRNA expression pathways that may help researchers to identify crucial disease mechanisms. This book is a review of the scientific findings of distinguished scholars who have studied NLRP3 inflammasome activation and its contribution in worsening the outcomes of inflammatory disorders. This collection of chapters covers many aspects of the multifaceted role of NLRP3 inflammasome. Beginning with airway inflammation and fibrosis, it progresses to explore its involvement in pulmonary hypertension, heart diseases, tuberculosis, cardiovascular complications, and childhood asthma. Additionally, it examines the inflammasome's impact on protozoan parasitic infections and neuropathic pain. The chapters not only elucidate the intricate mechanisms of NLRP3 activation but also discuss potential inhibitors and therapeutic targets. Readers will gain a comprehensive understanding of the NLRP3 inflammasome's diverse implications across different physiological contexts. The book includes references making this book a valuable treatise of insights for researchers, clinicians, and healthcare professionals.
