Download or read book Osteoactivin Plays a Novel Role in Autophagy mediated Bone Homeostasis written by Fatima A. Jaber and published by . This book was released on 2018 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt: Osteoporosis is a disease affecting most the population all over the world. There are some medications to treat this disease but with side effects. For example, bisphosphonates therapy has side effects including osteonecrosis. Therefore, it is important to discover new medications that increase bone formation and decrease bone resorption. Osteoactivin was discovered in an osteopetrotic mutant rat model. Our lab found that osteoactivin acts as anabolic factor to stimulate bone formation by osteoblasts. Autophagy is a catabolic process that allows cells to eliminate unwanted material. Autophagy related proteins have shown to be important for bone cells. Loss of autophagy could lead to dysfunction in bone homeostasis. In this study, we used the autophagy mTOR-independent and dependent pathways to determine its effects on osteoblast differentiation in vitro ex-vivo, and in vivo. First, we treated mesenchymal stem cells (MSCs) and osteoblast with Trehalose (TH) and Rapamycin (R) in culture, and found an increase in osteoblast differentiation and function determined by alkaline phosphatase (ALP) staining, activity, mineralization, and upregulation of osteoblast related gene expression. We found that treatment with TH and R stimulates osteoblast differentiation. Furthermore, we determined that treatments with TH causes induction of autophagosome formation associated with creating of double membrane of autophagic vacuoles in MC3T3-E1 osteoblast-like cells. Next, we wanted to determine if autophagy is important for osteoactivin mediated signaling in osteoblast. Our results have shown that osteoactivin co-localizes with microtubule-associated protein light chain 3II (LC3II), the main marker for autophagosome formation. Furthermore, we found that treatment with TH and R caused new bone formation in neonatal calvarial organ cultures from DBA/2J GPNMB+ and DBA/2J mice. Lastly, we found that osteoactivin enhanced osteoblast differentiation through the autophagy signaling pathway.In the next study, we wanted to determine the role of osteoactivin on osteoclast differentiation and function by mTOR-independent and dependent pathways. Our results revealed that osteoactivin inhibits osteoclast differentiation and size through mTOR-independent pathway but increases osteoclast function by the mTOR-dependent pathway in vitro study by TRAP staining and activity. While in vivo study showed that both autophagy pathways (mTOR-independent and dependent) causes increased osteoclast differentiation and bone resorption by TRAP staining and [mu]CT. Taken together, we believe that the osteoactivin and mTOR-dependent pathway rapamycin interact with each other to increase osteoblast differentiation, bone formation and osteoclast mediated resorption. However, mTOR-independent pathway by TH causes increased osteoblast differentiation, bone formation, and osteoclast differentiation.
Download or read book Webvision written by Helga Kolb and published by . This book was released on 2007 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Bone Toxicology written by Susan Y. Smith and published by Springer. This book was released on 2017-09-27 with total page 479 pages. Available in PDF, EPUB and Kindle. Book excerpt: The content of this book is intended to provide the toxicologist in drug development in the pharmaceutical and biotechnology industries with a broad understanding of bone and its interactions with other organ systems in safety assessments. The book is divided into three parts. The first part describes our current understanding of bone biology and its primary regulatory pathways. Additional chapters address regulatory and study design considerations for incorporating bone end points in toxicology studies, with special consideration being given to juvenile toxicology studies. This is intended to address recent regulatory requirements to evaluate skeletal development for drugs in development for pediatric populations. The second part of the book describes the principal techniques and methods used in bone research; understanding how these end-points are derived is fundamental to their appropriate application. These first two parts of the book provide the background and the means to develop the concepts in part three which describes bone and its interaction with other organ systems. The unique series of chapters in part three, contributed to by key leaders in their respective fields and in bone research, provides a comprehensive collective work. Although constantly evolving, the crosstalk and interaction of the skeleton with several organ systems is now recognized and well documented, such as for the reproductive system, muscle and kidney, while our understanding of the interaction with other organ systems, such as the immune system and CNS, is in its infancy. Recent work highlights the key role of the skeleton in the regulation of energy metabolism and the impact this has on research in metabolic diseases such as obesity and diabetes. The hope is that this book will enlighten many and encourage more to explore the impact of new compounds on the skeleton in the development of effective and safe drugs.
Download or read book Epigenetics in Human Disease written by Trygve Tollefsbol and published by Academic Press. This book was released on 2012-07-26 with total page 617 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetics is one of the fastest growing fields of sciences, illuminating studies of human diseases by looking beyond genetic make-up and acknowledging that outside factors play a role in gene expression. The goal of this volume is to highlight those diseases or conditions for which we have advanced knowledge of epigenetic factors such as cancer, autoimmune disorders and aging as well as those that are yielding exciting breakthroughs in epigenetics such as diabetes, neurobiological disorders and cardiovascular disease. Where applicable, attempts are made to not only detail the role of epigenetics in the etiology, progression, diagnosis and prognosis of these diseases, but also novel epigenetic approaches to the treatment of these diseases. Chapters are also presented on human imprinting disorders, respiratory diseases, infectious diseases and gynecological and reproductive diseases. Since epigenetics plays a major role in the aging process, advances in the epigenetics of aging are highly relevant to many age-related human diseases. Therefore, this volume closes with chapters on aging epigenetics and breakthroughs that have been made to delay the aging process through epigenetic approaches. With its translational focus, this book will serve as valuable reference for both basic scientists and clinicians alike. Comprehensive coverage of fundamental and emergent science and clinical usage Side-by-side coverage of the basis of epigenetic diseases and their treatments Evaluation of recent epigenetic clinical breakthroughs
Download or read book Pharmacoepigenetics written by Ramón Cacabelos and published by Academic Press. This book was released on 2019-06-04 with total page 986 pages. Available in PDF, EPUB and Kindle. Book excerpt: Pharmacoepigenetics provides a comprehensive volume on the role of epigenetics and epigenomics in drug discovery and development, providing a detailed, but accessible, view of the field, from basic principles, to applications in disease therapeutics. Leading international researchers from across academia, clinical settings and the pharmaceutical industry discuss the influence of epigenetics and epigenomics in human pathology, epigenetic biomarkers for disease prediction, diagnosis, and treatment, current epigenetic drugs, and the application of epigenetic procedures in drug development. Throughout the book, chapter authors offer a balanced and objective discussion of the future of pharmacoepigenetics and its crucial contribution to the growth of precision and personalized medicine. - Fully examines the influence of epigenetics and epigenomics in human pathology, epigenetic biomarkers for disease prediction, diagnosis, treatment, current epigenetic drugs and the application of epigenetic procedures in drug development - Features chapter contributions from leading international researchers in academia, clinical settings and the pharmaceutical industry - Instructs researchers, students and clinicians on how to better interpret and employ pharmacoepigenetics in drug development, efficiency and safety - Provides a balanced and objective discussion of the future of pharmacoepigenetics and its crucial role in precision medicine
Download or read book Innovations for Next Generation Antibody Drug Conjugates written by Marc Damelin and published by Springer. This book was released on 2018-05-29 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: Antibody-drug conjugates (ADCs) stand at the verge of a transformation. Scores of clinical programs have yielded only a few regulatory approvals, but a wave of technological innovation now empowers us to overcome past technical challenges. This volume focuses on the next generation of ADCs and the innovations that will enable them. The book inspires the future by integrating the field’s history with novel strategies and cutting-edge technologies. While the book primarily addresses ADCs for solid tumors, the last chapter explores the emerging interest in using ADCs to treat other diseases. The therapeutic rationale of ADCs is strong: to direct small molecules to the desired site of action (and away from normal tissues) by conjugation to antibodies or other targeting moieties. However, the combination of small and large molecules imposes deep complexity to lead optimization, pharmacokinetics, toxicology, analytics and manufacturing. The field has made significant advances in all of these areas by improving target selection, ADC design, manufacturing methods and clinical strategies. These innovations will inspire and educate scientists who are designing next-generation ADCs with the potential to transform the lives of patients.
Download or read book Inflammation and tendon healing written by Parmis Blomgran and published by Linköping University Electronic Press. This book was released on 2017-10-30 with total page 45 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tendons heal through three different overlapping phases; the inflammatory, proliferative and remodeling phase. Many studies have investigated what factors influence healing of tendons. However, little was known about inflammation and the immune cells present during Achilles tendon healing by the time this thesis started. We developed a flow cytometry method for our rat model of tendon healing, which enabled us to study different leukocyte subpopulations during Achilles tendon healing. The general aim of this thesis was to understand more about inflammation and the immune cell populations present during tendon healing and how the immune cell composition changes during normal tendon healing. Moreover, we investigated how different factors that are known to influence tendon healing affected the composition of the immune cell population. First, we described the immune cells during the time course of tendon healing focusing on different subpopulations of macrophages and T cells. Then, we studied how these cells were influenced by reduced mechanical loading. Mechanical loading prolonged the presence of M1 macrophages and delayed the switch to regulatory T cells and M2 macrophages compared to reduced mechanical loading. Next, the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the leukocyte composition revealed that, even though NSAIDs influence the mechanical properties of healing tendon, this effect was not mediated via changes in the leukocyte sub-populations during early and mid-time tendon healing. Further, the effect of corticosteroids during the inflammatory and remodeling phases of tendon healing was an improved healing of tendons and a reduction of CD8a T cells when corticosteroid was administered after the inflammatory phase. Lastly, we investigated if impairment of tendon healing by NSAIDs was related to mechanotransduction or microdamage during mechanical loading and showed that NSAIDs impair tendon healing by reducing the response to microdamage. In conclusion, these studies show that inflammation plays an important role during Achilles tendon healing, and factors that influence healing can also alter the presence or polarization of immune cell populations.
Download or read book Radionuclide and Hybrid Bone Imaging written by Ignac Fogelman and published by Springer. This book was released on 2013-01-03 with total page 1029 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book, written by authors with national and international reputations in the field, covers all aspects of radionuclide and hybrid bone imaging. Introductory sections present the basic science and consider the current status and limitations of conventional radiological techniques. The underlying principles of PET-CT and SPECT-CT are carefully explained, and the value of different PET and SPECT tracers, assessed. The role of single- and dual-modality approaches in the imaging of benign bone diseases and malignancies is then discussed in detail in a series of well-illustrated chapters. The pathologies addressed include metabolic bone disease, arthritis, bone and joint infections, primary bone and soft tissue tumors, and metastases from breast and prostate cancer. A further section considers the role of bone scintigraphy in the pediatric patient, and the closing chapters focus on miscellaneous subjects, including bone densitometry and radionuclide targeted therapy.
Download or read book Reviews on New Drug Targets in Age Related Disorders written by Paul C. Guest and published by Springer Nature. This book was released on 2021-03-16 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt: Aging is an inevitable part of life, and is becoming a worldwide social, economic and health problem due to the fact that an increasing proportion of individuals in the advanced age category have a higher probability of developing age-related disorders. New therapeutic approaches are still in need to decrease or slow the effects of such diseases in this aging society. Advances in ‘omic technologies such as genomics, transcriptomics, proteomics and metabolomics have significantly advanced our understanding of diseases in multiple medical areas. It is hoped that emerging hits from these analyses might be prioritized for further screening as potential novel drug targets for increasing the human healthspan in line with the lifespan, which will in turn lead to new therapeutic strategies and drug development projects by the pharmaceutical industry. This new book presents a series of reviews describing studies which have resulted in the identification of potential new drug targets for age-related disorders. Much of this information has come from ‘omic comparisons of healthy and disease states or from testing the effects of potential new therapeutic approaches. Each chapter will be presented in the context of specific chronic diseases or different therapeutic strategies, providing important information on disease mechanisms related to the aging process. This book will be of interest to researchers in the areas of aging and chronic disease, as well as clinical scientists, physicians, and major drug companies. With contributors from Australia, Brazil, Canada, France, Germany, India, Iran, Iraq, South Africa, South Korea, Thailand, Ukraine, United Kingdom, United States of America, Uruguay and Vietnam, this is a timely follow up to Guest’s previous book Reviews on New Drug Targets in Age-Related Disorders.
Download or read book T Cells in Arthritis written by P. Miossec and published by Springer Science & Business Media. This book was released on 1998-07-21 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt: Rheumatoid arthritis (RA) is the most common and most severe form of inflammatory arthritis. The pathogenesis of RA has been the subject of intense research for several decades. The prevailing hypotheses have changed over the years, and have attempted to incorporate the most recent data. Although T cells represent an important component of the cells which infiltrate the joint synovium, their contribution at a late stage of the disease remains a matter of debate. The goal of this book is to outline the major arguments and data suggesting that T cells may, or may not, be central players in the pathogenesis of chronic RA. While each of the editors and authors has his/her own bias (as will be clear by reading the respective chapters), our hope is that the readers will enjoy a complete and balanced view of the critical questions and experiments. This is not just an intellectual exercise since the direction of future therapeutic interventions depends heavily on how one interprets the pathogenesis of RA and the contribution of T cells.
Download or read book Limbic predominant Age related TDP 43 Encephalopathy written by Beller Health and published by Independently Published. This book was released on 2019-05-13 with total page 114 pages. Available in PDF, EPUB and Kindle. Book excerpt: Book 9 focuses on a new dementia type, LATE, mistaken as Alzheimer's disease until now.LATE stands for Limbic-predominant age-related TDP-43 encephalopathy, the protein buildup responsible for this dementia. This book is organic, like the series, meaning we never consider our books as finished. Science evolves, which is why our books go through continuous updates. Since LATE is a new dementia classification, we expect continuous further information to emerge. Watch Amazon alerts for potential digital updates. We provide free digital copies on all paperback purchases, so everybody receives free updates.
Download or read book Pulmonary Metastasis written by Leonard Weiss and published by Macmillan Reference USA. This book was released on 1978 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Handbook of Innovations in Central Nervous System Regenerative Medicine written by António Salgado and published by Elsevier. This book was released on 2020-06-10 with total page 712 pages. Available in PDF, EPUB and Kindle. Book excerpt: Handbook of Innovations in CNS Regenerative Medicine provides a comprehensive overview of the CNS regenerative medicine field. The book describes the basic biology and anatomy of the CNS and how injury and disease affect its balance and the limitations of the present therapies used in the clinics. It also introduces recent trends in different fields of CNS regenerative medicine, including cell transplantation, bio and neuro-engineering, molecular/pharmacotherapy therapies and enabling technologies. Finally, the book presents successful cases of translation of basic research to first-in-human trials and the steps needed to follow this path. Areas such as cell transplantation approaches, bio and neuro-engineering, molecular/pharmacotherapy therapies and enabling technologies are key in regenerative medicine are covered in the book, along with regulatory and ethical issues. - Describes the basic biology and anatomy of the CNS and how injury and disease affect its balance - Discusses the limitations of present therapies used in the clinics - Introduces the recent trends in different fields of CNS regenerative medicine, including cell transplantation, bio and neuro-engineering, molecular/pharmacotherapy therapies, and enabling technologies - Presents successful cases of translation of basic research to first-in-human trials, along with the steps needed to follow this path
Download or read book Amyloid and Related Disorders written by Maria M. Picken and published by Humana Press. This book was released on 2015-08-17 with total page 536 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of this text presents an overview of the most recent developments in this area including clinical presentation, etiology, pathogenesis, and differential diagnosis. The rationale for various therapies, including transplantation, is discussed and tissue diagnosis (its pitfalls and strategies for avoiding them) and laboratory support are included. The involvement of all major organ systems including renal/genitourinary, cardiac, gastrointestinal, pulmonary, peripheral nerve/central nervous system, soft tissue, skin, lymph node/spleen and bone marrow pathology is also covered. Amyloid and Related Disorders, Second Edition will be invaluable to specialized and general pathologists as well as cytopathologists. Other medical professionals may also benefit from this concise update on the systemic amyloidoses.
Download or read book Sphingolipids as Signaling and Regulatory Molecules written by Charles Chalfant and published by Springer Science & Business Media. This book was released on 2011-01-12 with total page 311 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book attempts to analyze the latest discoveries in sphingolipid biology and how the alteration of their metabolism leads to altered signaling events and to the development of pathobiological disorders, such as cancer, cardiovascular diseases, asthma, diabetes, inflammation and infectious diseases.
Download or read book Cancer related Bone Pain written by Andrew Davies and published by OUP Oxford. This book was released on 2007-11-15 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer-related bone pain is experienced by patients with primary bone tumours such as myeloma and osteosarcoma, but is more commonly seen in patients with malignant tumours that have metastasised to bone. Bone pain is one of the most common and severe forms of pain associated with breast, prostate and lung cancer, yet little is known about the underlying mechanisms responsible for the pain. Cancer patients identify bone pain as the most disruptive cancer-related event in terms of their quality of life and daily functioning, and it is also associated with increased incidence of morbidity, depression, and anxiety. Part of the Oxford Pain Management Library, this volume summarises the latest evidence-based and practical information on the management of cancer-related bone pain. Chapters cover the pathophysiology and clinical features of bone pain, general principles of management and the use of opioids and other agents. It will be an invaluable reference for all health care professionals involved in the management of patients with bone pain from various disciplines including palliative care, anaesthetics, oncology and general practice.
Download or read book Protein Homeostasis written by Richard I. Morimoto and published by . This book was released on 2012 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proper folding of proteins is crucial for cell function. Chaperones and enzymes that post-translationally modify newly synthesized proteins help ensure that proteins fold correctly, and the unfolded protein response functions as a homeostatic mechanism that removes misfolded proteins when cells are stressed. This book covers the entire spectrum of proteostasis in healthy cells and the diseases that result when control of protein production, protein folding, and protein degradation goes awry.
