Download Free Jak Stat Pathway In Disease Book in PDF and EPUB Free Download. You can read online Jak Stat Pathway In Disease and write the review.

This book reviews current understanding of the biological roles of the signal transducer and activator of transcription (STAT) proteins and their dysregulation in diseases. STAT proteins were named after their role as signal transducers and activators of transcription. STAT proteins are highly conserved among species, thus reflecting the importance
JAK tyrosine kinases and STAT transcription factors constitute a signaling pathway, which is activated by cytokines. By activating gene transcription it regulates essential biological responses to environmental cues. The Jak-Stat pathway is involved in the regulation of cell development, differentiation, proliferation and apoptosis. Improper function may contribute to hematopoietic malignancies and cancer. This book provides comprehensive insights into the latest basic and clinical developments in the field. The first part reviews recent findings and new technologies pertaining to basics of Jak-Stat function. The second part describes the evolution of Jak-Stat signaling and the role of the pathway in invertebrate organisms. The third part focuses on Jak-Stat signaling in hematopoietic cells under both physiological and pathophysiological conditions. Finally, chapters in the fourth section describe the relationship of Jak-Stat signaling to various states of disease, particularly infection, leukemias and solid cancers. The book is intended for all scientists in molecular biology, biochemistry and cell biology dealing with biomedical issues.
JAK-STAT pathway is one of the few signal transduction pathways that transduce signals involved in multiple homeostatic biological processes including cell differentiation and proliferation, cell death, hematopoiesis and immune responses. JAK-STAT is an elegant pathway that is relatively simple and evolutionary conserved as gene expression is regulated by external parameters. Activated by growth factors or cytokines, this signal transduction cascade regulates the transcription of genes at the nucleus. Mutations and polymorphisms in JAK-STAT pathway are associated with inflammatory diseases and cancers that could impede regular homeostasis. Features: Details activation and microRNA-mediated regulation of JAK-STAT pathway Provides exclusive information about the association of the pathway in various diseases including allergic inflammation, neuro-inflammatory disorder, atopic dermatitis hematopoietic malignancies, cardiovascular disorder, renal disorder, immunodeficiency, liver fibrosis, diabetes and obesity that affect individuals across the globe Clinical relevance of the signaling cascade has been discussed in context of novel class of therapeutics that targets this pathway. An overview of JAK-STAT signaling pathway and the structure-function relationship of different domains of the cascade are discussed. This book provides detailed information on various diseases that are associated with JAK-STAT pathway. It will act as a very good reference book for basic science researchers, academicians, industry professionals involved in translational research leading to product development. This book will excite future professionals towards better understanding of the regulation of this pathway, its association with other signaling cascades to design novel therapeutics.
This book for the first time comprehensively surveys the research investigating the Jak-Stat pathway and its role in normal blood development as well as its perturbation in disease. It draws on the expertise of world-renowned medical researchers to take the reader from basic biology through to recent therapeutic advances.
Performing a surgical operation must be one of the most complex motor tasks undertaken by humans. To the student rotating on a third-year clerkship, or to the resident beginning a surgical career, the complexity can no doubt be daunting. It is the goal of this handbook to try to bring some degree of order to the complexity, focusing on many of the common operations in general, plastic, thoracic, and vascular surgery, and in organ transplantation. We have done so by dividing each procedure into specific and well-defined steps.
Dysregulation of the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is critically involved in the pathogenesis of multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE). Suppressor Of Cytokine Signaling (SOCS) proteins are the negative regulators of the JAK/STAT pathway. To determine the role of SOCS3 in myeloid cells in EAE, mice with conditional SOCS3 deletion in myeloid cells (LysMCre-SOCS3fl/fl) were created and tested. LysMCre-SOCS3fl/fl mice develop a severe, non-resolving atypical form of disease, characterized by lesions and extensive neutrophil and other inflammatory cell infiltrates in the cerebellum and brainstem, elevated STAT activation, elevated cytokine, chemokine and iNOS expression, and prominent axonal damage. Mechanistically, loss of SOCS3 leads to a pronounced polarization to the pro-inflammatory macrophage (M1) phenotype, which promotes T-cell proliferation and polarization to Th1 and Th17 phenotypes, and has functional consequences for neurons. Cerebellum- and brainstem-infiltrating SOCS3-deficient neutrophils play a critical role in mediating atypical EAE development. Antibody-mediated depletion of neutrophils and blocking CXCR2 signaling ameliorates atypical EAE development. Functionally, SOCS3-deficient neutrophils produce high levels of CXCL2, CCL2, CXCL10, nitric oxide (NO), TNF-a and IL-1b, recruiting themselves and other inflammatory infiltrates into the cerebellum and brainstem and creating a pro-inflammatory environment. Importantly, neutrophils may have a direct pathogenic role in driving axonal damage by local production of NO. As dysregulation of the JAK/STAT pathway has been implicated in MS/EAE, we utilized AZD1480, a JAK1/2 small molecule inhibitor, to investigate its therapeutic potential in models of EAE. Inhibition of JAK1/2 restrains pro-inflammatory responses in both T cells and myeloid cells. AZD1480 treatment suppresses differentiation of Th1 and Th17 cells and exerts an inhibitory effect on M1 polarization. Using AZD1480 for proof-of-principle, we demonstrate that inhibiting the JAK/STAT pathway has striking clinical efficacy in five EAE models: classical EAE, atypical EAE, relapsing-remitting (RR)-EAE, Th1 cell-mediated EAE, and Th17 cell-mediated EAE. In conclusion, these studies reveal a role for SOCS3 in myeloid cells to provide protection against detrimental inflammatory responses in the central nervous system. In addition, our data suggest the feasibility of the JAK/STAT pathway as a therapeutic target for neuroinflammatory diseases.
Written by leading experts in the field and designed for dermatologists and residents, this book includes evidence-based medicine that underscores the clinical data, as well as practical tips on how to use both biologic and systemic agents in the field of dermatology. In the past decade, there have been several groundbreaking advances in medical dermatology. Novel biologic and systemic agents have been developed to treat inflammatory disorders, including psoriasis and atopic dermatitis, as well as skin malignancies such as melanoma. Biologic and Systemic Agents in Dermatology encompasses these developments by describing the mechanism of action of these various agents and the clinical efficacy and safety to treating these respective disorders. The utilization of biologic and systemic agents in other dermatologic conditions, pharmacoeconomics, pharmacovigilance, and clinical trials outcomes are discussed as well as topics including tumor necrosis, conventional systemic agents for psoriatic disease, and oral agents for atopic dermatitis.
This book uniquely relates the broad impact of signal transduction research on the understanding and treatment of human disease. There have been significant advances in the area of signaling in disease processes, yet no resource presently connects these advances with understanding of disease processes and applications for novel therapeutics. Given the emphasis on translational research and biological relevance in biotechnology, and, conversely, the importance of molecular approaches for clinical research, it is evident that a single resource bridging signaling research and human disease will be invaluable.
The pathogenesis of both forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis, depends on complex immune abnormalities, and the investigation of cytokines has become critical to basic, clinical and therapeutic aspects of these enigmatic entities. This book offers clear, concise, state-of-the-art information on the role of various immunoregulatory and pro-inflammatory mediators in Crohn's disease and ulcerative colitis. Each cytokine is analyzed in regard to pathogenic and clinical implications, taking advantage of information derived from patients, animal models, as well as immunological and molecular in vitro systems. This volume is of interest to gastroenterologists, clinical investigators, immunologists, cell biologists and any professional interested in mucosal immunity and inflammation.