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Obesity is increasing in epidemic proportions worldwide. A low-grade inflammation caused by obesity leads to its many inflammation-associated complications, including insulin resistance, type 2 diabetes, accelerated atherosclerosis, nonalcoholic steatohepatitis that can lead to liver cirrhosis, heart failure, cancer, and Alzheimer’s disease. This systemic inflammation is due to profound changes in the adipose tissue microenvironment, at the heart of which is the adipocyte. Increasing evidence suggests the adipocyte not only stores excess energy, but initiates an escalating pro-inflammatory cascade in adipose tissue during high-fat diet. The adipocyte secretes over 50 cytokines and hormones that both enhance and suppress inflammation, secretes extracellular matrix proteins that impact inflammation, produces and releases toxic lipids that aggravate inflammation, and, more recently, was shown to present antigen to activate CD4+ T cells. Although discovered several decades ago, studies continue to identify pro-inflammatory roles for leptin and anti-inflammatory activities for adiponectin, hormones secreted in large amounts by the adipocyte.
Due to the resultant health consequences and considerable increase in prevalence, obesity has become a major worldwide health problem. “Obesity and Lipotoxicity” is a comprehensive review of the recent researches to provide a better understanding of the lipotoxicity-related mechanisms of obesity and the potential for the development of new treatment strategies. This book overviews the biochemical pathways leading to obesity-related metabolic disorders that occur subsequent to lipotoxicity. Chapters examine the deleterious effects of nutrient excess at molecular level including the cellular and molecular aspects of breast cancer, resistance to leptin, insulin, adiponectin, and interconnection between the circadian clock and metabolic pathways during high-fat feeding. “Lipotoxicity and Obesity” will be a useful resource for clinicians and basic science researchers, such as biochemists, toxicologists, immunologists, nutritionists, adult and pediatric endocrinologists, cardiologists, as well as students who are thought in this field.
During the past decade, a wide range of scientific disciplines have adopted the use of adipose-derived stem/stromal cells (ASCs) as an important tool for research and discovery. In Adipose-Derived Stem Cells: Methods and Protocols, experts from the field, including members of the esteemed International Federation of Adipose Therapeutics and Science (IFATS), provide defined and established protocols in order to further codify the utilization of these powerful and accessible cells. With chapters organized around approaches spanning the discovery, pre-clinical, and clinical processes, much of the emphasis is placed on human ASC, while additional techniques involving small and large animal species are included. As a volume in the highly successful Methods in Molecular BiologyTM series, the detailed contributions include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Adipose-Derived Stem Cells: Methods and Protocols serves as a vital reference text for experienced researchers as well as new students on the path to further exploring the incredible potential of ASCs.
This timely and most comprehensive reference available on the topic covers all the different aspects vital in the fight against the global obesity epidemic. Following a look at adipose tissue development and morphology, the authors go on to examine its metabolic and endocrine functions and its role in disease. The final section deals with comparative and evolutionary aspects of the tissue. The result is an essential resource for cell and molecular biologists, physiologists, biochemists, pharmacologists, and those working in the pharmaceutical industry.
This reference work presents the origins of cells for tissue engineering and regeneration, including primary cells, tissue-specific stem cells, pluripotent stem cells and trans-differentiated or reprogrammed cells. There is particular emphasis on current understanding of tissue regeneration based on embryology and evolution studies, including mechanisms of amphibian regeneration. The book covers the use of autologous versus allogeneic cell sources, as well as various procedures used for cell isolation and cell pre-conditioning , such as cell sorting, biochemical and biophysical pre-conditioning, transfection and aggregation. It also presents cell modulation using growth factors, molecular factors, epigenetic approaches, changes in biophysical environment, cellular co-culture and other elements of the cellular microenvironment. The pathways of cell delivery are discussed with respect to specific clinical situations, including delivery of ex vivo manipulated cells via local and systemic routes, as well as activation and migration of endogenous reservoirs of reparative cells. The volume concludes with an in-depth discussion of the tracking of cells in vivo and their various regenerative activities inside the body, including differentiation, new tissue formation and actions on other cells by direct cell-to-cell communication and by secretion of biomolecules.
Inflammation has become one of the most exciting and rewarding areas of medical research. Recent years have seen a revolution in our understanding of how blood and tissue cells interact and of the intracellular mechanisms controlling their activation. This has revealed the underlying inflammatory pathology of many diseases and provided multiple new targets for anti-inflammatory and immunomodulatory therapy. The Encyclopedia of Inflammatory Diseases will cover the following areas: Inflammatory Processes and Cells Inflammatory Diseases Mediators of Inflammation Pharmacology of Inflammation Since inflammatory diseases and their therapy cover a broad range of scientific and medical fields, the encyclopedia will be co-edited by four international experts, a clinician and three researchers from the disciplines of immunology, biochemistry, and pharmacology, in this way providing students, basic and clinical scientists and practitioners in academia, hospitals and industry with valuable interlinked information. This living project will serve as a reliable and comprehensive data pool for everybody working in inflammation research. Owing to its dynamic nature, it will grow with time and future editions, becoming an indispensible source of information for academia, clinical practitioners and industry.
Over the past decade, significant efforts have been made to develop stem cell-based therapies for difficult to treat diseases. Multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), appear to hold great promise in regards to a regenerative cell-based therapy for the treatment of these diseases. Currently, more than 200 clinical trials are underway worldwide exploring the use of MSCs for the treatment of a wide range of disorders including bone, cartilage and tendon damage, myocardial infarction, graft-versus-host disease, Crohn’s disease, diabetes, multiple sclerosis, critical limb ischemia and many others. MSCs were first identified by Friendenstein and colleagues as an adherent stromal cell population within the bone marrow with the ability to form clonogenic colonies in vitro. In regards to the basic biology associated with MSCs, there has been tremendous progress towards understanding this cell population’s phenotype and function from a range of tissue sources. Despite enormous progress and an overall increased understanding of MSCs at the molecular and cellular level, several critical questions remain to be answered in regards to the use of these cells in therapeutic applications. Clinically, both autologous and allogenic approaches for the transplantation of MSCs are being explored. Several of the processing steps needed for the clinical application of MSCs, including isolation from various tissues, scalable in vitro expansion, cell banking, dose preparation, quality control parameters, delivery methods and numerous others are being extensively studied. Despite a significant number of ongoing clinical trials, none of the current therapeutic approaches have, at this point, become a standard of care treatment. Although exceptionally promising, the clinical translation of MSC-based therapies is still a work in progress. The extensive number of ongoing clinical trials is expected to provide a clearer path forward for the realization and implementation of MSCs in regenerative medicine. Towards this end, reviews of current clinical trial results and discussions of relevant topics association with the clinical application of MSCs are compiled in this book from some of the leading researchers in this exciting and rapidly advancing field. Although not absolutely all-inclusive, we hope the chapters within this book can promote and enable a better understanding of the translation of MSCs from bench-to-bedside and inspire researchers to further explore this promising and quickly evolving field.
Resistance to therapies, both targeted and systemic, and metastases to distant organs are the underlying causes of breast cancer-associated mortality. The second edition of Breast Cancer Metastasis and Drug Resistance brings together some of the leading experts to comprehensively understand breast cancer: the factors that make it lethal, and current research and clinical progress. This volume covers the following core topics: basic understanding of breast cancer (statistics, epidemiology, racial disparity and heterogeneity), metastasis and drug resistance (bone metastasis, trastuzumab resistance, tamoxifen resistance and novel therapeutic targets, including non-coding RNAs, inflammatory cytokines, cancer stem cells, ubiquitin ligases, tumor microenvironment and signaling pathways such as TRAIL, JAK-STAT and mTOR) and recent developments in the field (epigenetic regulation, microRNAs-mediated regulation, novel therapies and the clinically relevant 3D models). Experts also discuss the advances in laboratory research along with their translational and clinical implications with an overarching goal to improve the diagnosis and prognosis, particularly that of breast cancer patients with advanced disease.
This book highlights the important role free fatty acids (FFA) play as potential drug targets. While FFA have long been considered byproducts of cell metabolism, they are now recognized as ligands that regulate cell and tissue function via G-protein-coupled receptors. At least three receptors have been identified for which FFA appear to be the endogenous ligands.
The inverse correlation between allergic diseases and helminth infections has been debated for over 30 years. It was initially assumed that the underlying mechanism is an imbalance between Th1 and Th2 responses that, as a result of reduced exposure to Th1-inducing infectious pathogens, has tipped to allergic Th2 responses. It has only recently been clearly demonstrated that helminth infections have negative effects on allergic disease manifestation. This was shown to be consistent with the activity of regulatory cell populations, which control the effector mechanisms of both Th1 and Th2. In th.