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• Author : Beth Levine,Tamotsu Yoshimori,Vojo Deretic
• Publisher :Unknown
• Release Date :2009-10-03
• Total pages :339
• ISBN : 3642003028

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Summary : Autophagy is a fundamental biological process that enables cells to autodigest their own cytosol during starvation and other forms of stress. It has a growing spectrum of acknowledged roles in immunity, aging, development, neurodegeneration, and cancer biology. An immunological role of autophagy was first recognized with the discovery of autophagy’s ability to sanitize the cellular interior by killing intracellular microbes. Since then, the repertoire of autophagy’s roles in immunity has been vastly expanded to include a diverse but interconnected portfolio of regulatory and effector functions. Autophagy is an effector of Th1/Th2 polarization; it fuels MHC II presentation of cytosolic (self and microbial) antigens; it shapes central tolerance; it affects B and T cell homeostasis; it acts both as an effector and a regulator of Toll-like receptor and other innate immunity receptor signaling; and it may help ward off chronic inflammatory disease in humans. With such a multitude of innate and adaptive immunity functions, the study of autophagy in immunity is one of the most rapidly growing fields of contemporary immunological research. This book introduces the reader to the fundamentals of autophagy, guides a novice and the well-informed reader alike through different immunological aspects of autophagy as well as the countermeasures used by highly adapted pathogens to fight autophagy, and provides the expert with the latest, up-to-date information on the specifics of the leading edge of autophagy research in infection and immunity.

• Author : Daniel Klionsky
• Publisher :Unknown
• Release Date :2009-03-05
• Total pages :560
• ISBN : 0080923259

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Summary : This is the companion volume to Daniel Klionsky’s Autophagy: Lower Eukaryotes, which features the basic methods in autophagy covering yeasts and alternative fungi (aspergillus, podospora, magnaporthe). Klionsky is one of the leading authorities in the field. He is the editor-in-chief of Autophagy. The November 2007 issue of Nature Reviews highlighted his article, “Autophagy: From phenomenology to molecular understanding in less than a decade. He is currently editing guidelines for the field, with 230 contributing authors, that will publish in Autophagy. Particularly in times of stress, like starvation and disease, higher organisms have an internal mechanism in their cells for chewing up and recycling parts of themselves. The process of internal “house cleaning in the cell is called autophagy – literally self-eating. Breakthroughs in understanding the molecular basis of autophagy came after the cloning of ATG1 (autophagy-related gene 1) in yeast. (To date, 30 additional yeast genes have been identified.) These ATG genes in yeast were the stepping stones to the explosion of research into the molecular analysis of autophagy in higher eukaryotes. In the future, this research will help to design clinical approaches that can turn on autophagy and halt tumor growth.

• Author : Daniel Klionsky
• Publisher :Unknown
• Release Date :2009-03-10
• Total pages :536
• ISBN : 0080958486

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Summary : The third and final installment of Daniel J. Klionsky's new three-volume treatment of autophagy, this volume focuses on monitoring autophagy with regard to disease connections, and presents methods that can be used to analyze autophagy in clinical samples. Edited by one of the leading authorities in the field, this volume and its companion volumes, Autophagy: Lower Eukaryotes and Autophagy in Mammalian Systems, provide a comprehensive overview of the techniques involved in studying autophagy in eukaryotes and simple animal systems, mammalian cells and non-human animals, and humans. Particularly in times of stress, like starvation and disease, higher organisms have an internal mechanism in their cells for chewing up and recycling parts of themselves. The process of internal “house cleaning in the cell is called autophagy – literally self-eating. In the future, research in this field will help to design clinical approaches that can turn on autophagy and halt tumor growth. * Provides an overview of autophagy in regards to humans, specifically regarding disease connections and clinical samples. * Includes methods to evaluate the role of autophagy in the drug-induced cell death of cancer cells in culture *Presents reliable methods that, in this relatively new field, allow the reader to find appropriate techniques to identify, monitor, and quantify autophagic processes

• Author : Anonim
• Publisher :Unknown
• Release Date :2011-09-02
• Total pages :808
• ISBN : 0080923267

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Summary : This is the companion volume to Daniel Klionsky’s Autophagy: Lower Eukaryotes, which features the basic methods in autophagy covering yeasts and alternative fungi. Klionsky is one of the leading authorities in the field. He is the editor-in-chief of Autophagy. The November 2007 issue of Nature Reviews highlighted his article, “Autophagy: from phenomenology to molecular understanding in less than a decade. He is currently editing guidelines for the field, with 230 contributing authors that will publish in Autophagy. Particularly in times of stress, like starvation and disease, higher organisms have an internal mechanism in their cells for chewing up and recycling parts of themselves. The process of internal “house-cleaning in the cell is called autophagy – literally self-eating. Breakthroughs in understanding the molecular basis of autophagy came after the cloning of ATG1 in yeast. These ATG genes in yeast were the stepping stones to the explosion of research into the molecular analysis of autophagy in higher eukaryotes. In the future, this research will help to design clinical approaches that can turn on autophagy and halt tumor growth. *Establishes the functional roles of specific cellular proteins in selective and nonselective autophagy in mammalian cells, which aides researchers in determining why autophagy is shut down in neoplastia (growth of abnormal tissue mass) and turned on during bacterial invasion *Includes methods to evaluate the role of autophagy in the drug-induced cell death of cancer cells in culture, which helps researchers design clinical approaches that can turn on autophagy and halt tumor growth *Covers higher eukaryotes including lifespan in C.elegans to marine organisms and bridging into the clinical aspects, including autophagy in chronic myelogenous leukemia (CML is one of four types of leukemia), lung cancer, prostate cancer, and cardiac cells.

• Author : Jun Ren,James R. Sowers,Yingmei Zhang
• Publisher :Unknown
• Release Date :2018-04-12
• Total pages :340
• ISBN : 9780128054420

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Summary : Autophagy and Cardiometabolic Diseases: From Moleculer Mechanisms to Translational Medicine covers the science of autophagy in relation to cardiometabolic diseases and the future therapeutic potentials of autophagy regulation in these processes. Processes are not described in isolation, but in concert with other cellular and/or metabolic processes, such as lipogenesis, glucose, energy metabolism and apoptosis. This approach recognizes the multifactorial nature of cardiometabolic diseases, including obesity, diabetes, insulin resistance, hypertension and dyslipidemia. The book provides explanations, while also distinguishing the delicate role for autophagy in pathogenesis and exploring complications for cardiometabolic diseases. By targeting autophagy, it offers new avenues for drug discovery and treatment for cardiometabolic anomalies. It is a perfect resource for cardiology researchers, scientists and medical practitioners. Explains the processes inherent in the protein quality control for pathogenesis and complications of cardiometabolic diseases Provides knowledge from internationally recognized contributors in the field Incorporates a translational approach, covering the basic cellular biology of autophagy and presenting the role of autophagy regulation for both pathogenesis and complication in cardiometabolic diseases Contains access to a companion website with additional illustrations

• Author : Hong-Gang Wang
• Publisher :Unknown
• Release Date :2013-03-30
• Total pages :261
• ISBN : 9781461465614

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Summary : With the explosion of information on autophagy in cancer, this is an opportune time to speed the efforts to translate our current knowledge about autophagy regulation into better understanding of its role in cancer. This book will cover the latest advances in this area from the basics, such as the molecular machinery for autophagy induction and regulation, up to the current areas of interest such as modulation of autophagy and drug discovery for cancer prevention and treatment. The text will include an explanation on how autophagy can function in both oncogenesis and tumor suppression and a description of its function in tumor development and tumor suppression through its roles in cell survival, cell death, cell growth as well as its influences on inflammation, immunity, DNA damage, oxidative stress, tumor microenvironment, etc. The remaining chapters will cover topics on autophagy and cancer therapy. These pages will serve as a description on how the pro-survival function of autophagy may help cancer cells resist chemotherapy and radiation treatment as well as how the pro-death functions of autophagy may enhance cell death in response to cancer therapy, and how to target autophagy for cancer prevention and therapy − what to target and how to target it. ​

• Author : Zhenyu Yue,Charleen T. Chu
• Publisher :Unknown
• Release Date :2012
• Total pages :426
• ISBN : 9789814350440

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Summary : What is autophagy? Why would neurons or other brain cells digest parts of themselves through autophagy? How can autophagy save the lives of cells under some conditions, but act as a culprit or accomplice to cell death in others? How does dysfunction of autophagy contribute to neurological diseases and can it be repaired or restored? This book addresses these questions and provide an expert view of the emerging concepts in autophagy research, focusing on autophagic processes and regulation in neurons. Current experimental evidence for both evolutionarily conserved and specialized regulatory mechanisms for autophagy in the mammalian nervous system will be presented. Advances in our understanding of the complex interplay of autophagy induction and downregulation will be discussed in relation to the critical balance needed to modulate neuroprotection versus neurodegeneration in the context of neurological diseases including Alzheimer's, Parkinson's, Huntington's, ischemic-hypoxic and lysosomal diseases.

• Author : M. A. Hayat
• Publisher :Unknown
• Release Date :2013-07-29
• Total pages :360
• ISBN : 9780124055353

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Summary : Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward thinking, these books offer a valuable guide to both cellular processes while inciting researchers to explore their potentially important connections. Considering that autophagy is associated with numerous biological processes, including cellular development and differentiation, cancer (both antitumor and protumor functions), immunity, infectious diseases, inflammation, maintenance of homeostasis, response to cellular stress, and degenerative diseases such as Alzheimer’s, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and prion diseases, there is a great need to understanding its role. Cell homeostasis is achieved by balancing biosynthesis and cellular turnover. In spite of the increasing importance of autophagy in various pathophysiological situations (conditions) mentioned above, this process remains underestimated and overlooked. As a consequence, its role in the initiation, stability, maintenance, and progression of these and other diseases (e.g., autoimmune disease) remains poorly understood. Volumes in the Series

• Author : Vojo Deretic
• Publisher :Unknown
• Release Date :2006-08-21
• Total pages :286
• ISBN : 9783527608546

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Summary : This first book to cover this new topic at the interface of cell biology, immunology and infection biology offers a unique insight as to how the innate and possibly the adaptive immune system are shaped by cellular mechanisms. Following a comprehensive introduction to autophagy, the work features cellular mechanisms and medical implications, structured according to all major pathogens, while also covering emerging infectious diseases, such as tuberculosis. Edited by one of the authors of a groundbreaking paper on this topic.

• Author : Roberta A. Gottlieb
• Publisher :Unknown
• Release Date :2012-12-31
• Total pages :240
• ISBN : 9780123851024

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Summary : Autophagy in Health and Disease offers an overview of the latest research in autophagy with a translational emphasis. This publication takes scientific research in autophagy a step further and offers integrated content with advancements in autophagy from cell biology and biochemical research to clinical treatments. A necessary reference for the bookshelf of medical and scientific researchers and students, Autophagy in Health and Disease presents high quality, reputable information on autophagy, allowing the reader quick access to the most applicable information. Discusses current understanding of the roles of autophagy in health and disease Covers the background of autophagy, the development of tools and therapeutics to measure and modulate autophagy, and autophagy in tissues and disease processes Features an accompanying website with figures and tables

• Author : William T. Jackson,Michele Swanson
• Publisher :Unknown
• Release Date :2015-02-16
• Total pages :352
• ISBN : 9781118677643

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Summary : The relationship between infection and immunity and autophagy, a pathway of cellular homeostasis and stress response, has been a rapidly growing field of study over the last decade. While some cellular processes are pro- or anti-infection, autophagy has been proven to be both: a part of the innate immune response against some microbes, and a cellular pathway subverted by some pathogens to promote their own replication. Autophagy, Infection, and the Immune Response provides a unified overview of the roles of cellular autophagy during microbial infection. Introductory chapters ground the reader by delineating the autophagic pathway from a cellular perspective, and by listing assays available for measuring autophagy. Subsequent chapters address virus interactions with autophagy machinery, the various roles of autophagy parasitic infection, and interactions of bacteria with the autophagic pathway. Concluding chapters explore the relationships of autophagy to systemic immune responses, including antigen presentation, ER stress, and production of IFN-gamma. Designed as a resource for those interested in initiating studies on the relationship between autophagy and infection or immunity, Autophagy, Infection, and the Immune Response combines practical state-of the art technique descriptions with an overview of the wide variety of known interactions between pathogens and the autophagic pathway.

• Author : Iman Tavassoly
• Publisher :Unknown
• Release Date :2015-02-16
• Total pages :79
• ISBN : 9783319149622

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Summary : This interdisciplinary thesis introduces a systems biology approach to study the cell fate decision mediated by autophagy. A mathematical model of interaction between Autophagy and Apoptosis in mammalian cells is proposed. In this dynamic model autophagy acts as a gradual response to stress (Rheostat) that delays the initiation of bistable switch of apoptosis to give the cells an opportunity to survive. The author shows that his dynamical model is consistent with existing quantitative measurements of time courses of autophagic responses to cisplatin treatment. To understand the function of this response in cancer cells, he has provided a systems biology experimental framework to study quantitative and dynamical aspects of autophagy in single cancer cells using live-cell imaging and quantitative fluorescence microscopy. This framework can provide new insights on function of autophagic response in cancer cells.

• Author : Cheng Yang
• Publisher :Unknown
• Release Date :2019
• Total pages :229
• ISBN : OCLC:1167740817

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Summary : Neurodegenerative diseases can be caused by abnormal protein accumulation, mitochondrial dysfunction and intracellular oxidative stress, all of which fall within the realm of autophagy, including autophagic clearance of protein aggregates and autophagic degradation of organelles (e.g. mitophagy). Although the exact mechanisms regulating autophagy in the central nervous system (CNS) remain unknown, it is likely that autophagy failure plays a critical role in the pathology of neurodegenerative disease. This study investigates the role of basal autophagy in oligodendrocyte (OL) development and OL function, focusing on autophagic activity in OL lineage cells and the effect of autophagy on OL production during OL development and in adulthood. It has been reported that myelinophagy, a recently discovered form of selective autophagy, is involved in the degradation of myelin and promotes myelin clearance in the peripheral nervous system (PNS). My current study also examines the role of autophagy in myelination, which has not yet been well investigated. We generate mice lacking autophagy related gene 5 (Atg5) specifically in OL lineage cells to study the role of autophagy in OL development and OL function. Employing immunostaining, electron microscopy and lipidomics analysis, we found that although the loss of autophagy does not have an evident effect on the proliferation and differentiation of OL precursors during OL development, it can cause abnormal aggregations of intracellular proteins in adult-born OLs with age, indicating that autophagy primarily affects adult-born OL function. In addition, a number of astrocytes become reactive in the cortex of these mice, which is the hallmark in response to the CNS pathologies, hinting at the importance of OL autophagy in maintaining brain homeostasis.

• Author : Thomas Hawthorn
• Publisher :Unknown
• Release Date :2019-06-24
• Total pages :126
• ISBN : 1230987654XX

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Summary : Discover how a one day starvation secret won the nobel prize. And how you can use it to lose weight and promote long-term health. In 2016, Yoshinori Ohsumi won the Nobel Prize for his research on Autophagy. Now, not only does autophagy have lifechanging weight loss benefits… It may help treat cancer and neurodegenerative diseases like Alzheimer’s. Why has this unique type of fasting only become established in the past couple of years? It’s simple, the fat cats of our food industry establishment have billions riding on the outdated “3 square meals a day” lifestyle. And not only is this typical American lifestyle outdated, it’s downright dangerous! However, there is another way. And inside this breakthrough book you’ll discover: How to lose weight faster while intermittent fasting IBS pain? You can blame this common food 5 superfoods you can find at your local supermarket How inflamed is your body right now? Exactly what to ask your doctor to find out the truth. How to increase autophagy without fasting for several days in a row 7 best foods for nurturing gut health Eat this “forgotten food” to reverse plaque build up in your arteries How to properly do a water fast without feeling weak or getting hungry. A handful of this food cuts risk of heart disease by 24% 1 in 4 supplements failed quality tests at a leading independent lab. Discover which ones to throw out How to lose weight without working out every day 3 beginner mistakes which actually prevent autophagy, and how to avoid them Do you get autophagy during 16/8 fasting? The surprising truth …and much, much more. Plus countless other health secrets… Including this “miracle beverage” which researchers at the University of Minnesota found lowered diabetes risk by 33%... drinking this also boosts the effectiveness of your fast… plus one drink to avoid which sneakily breaks your fast You’ll also discover How to avoid starvation mode while fasting The raw truth about extended water fasting Is too much autophagy bad? Get the answer from the world’s leading expert Why do dogs who eat 1 meal a day live 20% longer than dogs who eat 3 meals a day? The 3 benefits of autophagy you probably didn’t know about Autophagy success stories – how one obese Mom lost 90lbs in less than 6 months and cured her diabetes All written in plain English. So you don’t need a medical degree to understand and apply what’s inside. This is not just a diet fad. This is a long-term gamechanger in the health and longevity space. Here’s the deal. The traditional “calories in, calories out” weight loss method no longer works. And restrictive low-fat or vegan diets often leave you hungry and irritable. However, when you combine the keto diet with a 2016 Nobel Prize winning breakthrough known as autophagy – you get the keto diet on steroids So take control of your life and show your friends and family that there is a simple way to lose weight and be happy – scroll up and click “add to cart”

• Author : Aleth Coen
• Publisher :Unknown
• Release Date :2020-02-05
• Total pages :68
• ISBN : 1087864755

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Summary : In a day and age where we are bombarded with fad diets and new health discoveries, it is not always easy to figure out the best way to improve your health and longevity. Many diets claim that they can drastically improve your health, reduce your chances of developing cancer and cardiovascular disease, and cause weight loss, but few have the science to back them up like autophagy. By tapping into this process that has been designed to give you a low and healthy life, you can learn what Nobel-prize winning scientists already know: that autophagy is Nature's own panacea for a host of common ailments. In Autophagy: The Body's Natural Intelligence for Anti-Aging and Healing - Intermittent Fasting for Weight Kiss & Self-Cleansing, you will learn how you can achieve your health for longevity goals. The hard science behind this molecular process does not have to be intimidating. This book will explain it all in terms that even those without a science background can understand and use to their benefit. Autophagy is a natural process that the body utilizes to help you maintain a healthy equilibrium. Considered a type of non-apoptotic cell death, there are many benefits that this pathway confers that extend far beyond the realm of cell degradation. Indeed, autophagy is so common in the body and so easy to tap into that you may find yourself surprised that you had no heard of it before. Reading this book is the first step to changing your life. How many pathways can claim to lengthen your life while also causing you to lose weight. Not many. Your voyage into this exciting world starts here.

• Author : Akitoshi Nakashima
• Publisher :Unknown
• Release Date :2016
• Total pages :229
• ISBN : OCLC:1154196686

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Summary : Autophagy is an evolutionarily conserved process in eukaryotes by which cytoplasmic cargo sequestered inside double-membrane vesicles is delivered to the lysosome for degradation. In early pregnancy, trophoblasts and the fetus experience hypoxic and low-nutrient conditions; nevertheless, extravillous trophoblasts (EVTs) invade the uterine myometrium up to one-third of its depth and migrate along the lumina of spiral arterioles, replacing the maternal endothelial lining. An enhancement of autophagy induced by physiological hypoxia takes part in the invasion and vascular remodeling in EVTs. On the other hand, soluble endoglin, which increased in sera in preeclamptic cases, suppresses EVT-invasion or -vascular remodeling by inhibiting autophagy In vitro. In addition, a substance selectively degraded by autophagy, p62/SQSTM1, accumulates in EVT cells in preeclamptic placental biopsy samples showing impaired autophagy in vivo. Thus, alternation of autophagy could affect fates of mothers and babies. Recently increasing evidence of modulating autophagy has accumulated during pregnancy. In this chapter, we introduce the role of autophagy in embryogenesis, implantation, and maintaining pregnancy.

• Author : Peter Palese,Jean-Pierre Changeux
• Publisher :Unknown
• Release Date :2006-07-11
• Total pages :304
• ISBN : 9781402032424

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Summary : This book is an excellent, up-to-date reference on a relatively young area of research in which virology, cellular biology and molecular pathogenesis govern the principles of coinvestigation. Thus, the book will be of great interest to virologists, molecular immunologists and biologists, and biochemists but also to clinical pharmacologists in the long-term search for new antiviral agents. Ulrich Desselberger, Gif-sur-Yvette/Cambridge. Infection of a naïve (non-immune) host with a virus elicits an immediate response which results in a cascade of changes in the host, including an interferon response (innate immunity). The outcome of this interaction is influenced by the genes of the virus as well as the genes of the host. Interestingly, different viruses do it in different ways. Not only is there a plethora of mechanisms used by the invading organisms, but the host has also evolved a great variety of redundant and robust countermeasures. This interplay of host and virus represents one of the most significant frontiers in biology today. A clearer understanding of the mechanisms involved will arm us with better strategies to deal with viruses, including emerging pathogens and potential bioterrorism agents. This book is sure to benefit students, scientists, and physicians working in the areas of virology, immunology, microbiology, and infectious diseases. Pharmaceutical industry professionals will also find interest in this illuminating look into virus/host interactions.

• Author : Gerry Melino,David Vaux
• Publisher :Unknown
• Release Date :2010-02-22
• Total pages :316
• ISBN : 9780470686577

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Summary : This book on cell death contains 29 self-contained, peer-reviewed articles written by leading scientists in each field. It features overview articles aimed at undergraduates and non-specialists, which present basic information and provide entry into the following advanced articles. These advanced articles are written for postgraduate students and research workers, containing detailed information and key references allowing the reader to investigate a specific area in more depth. The book is an essential resource for educational purposes as well as a reference work for experienced researchers in the field. The articles will also be available electronically as part of the acclaimed Encyclopedia of Life Sciences (ELS). Key features: Provides a comprehensive overview on the research of programmed cell death. Edited by leaders in the field. Clearly written and illustrated articles. Full colour throughout. A spin-on to the acclaimed reference work, the Encyclopedia of Life Science (ELS). Combines introductory information with coverage of the latest discoveries in the field. Features overview level articles for advanced students or people new to a topic and more advanced articles for those requiring more detailed information. Serves as a reference work for advanced students as well as researchers in this field. Ideal library purchase for science, medical, and technology libraries in academia, government, and industry; medical libraries; networks and consortia covering these markets.

• Author : Anonim
• Publisher :Unknown
• Release Date :2018
• Total pages :229
• ISBN : OCLC:1051334734

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Summary : Abstract : Scope: Resveratrol (RSV) has been described as a potent antioxidant, antisteatotic, and antitumor compound, and it has also been identified as a potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary flavonoid with known antitumor, anti‐inflammatory, and antidiabetic effects. Additionally, QCT increases autophagy. To study the hypothetical synergistic effect of both compounds, we test the combined effect of QCT and RSV on the autophagy process in HepG2 cells. Methods and results: Autophagy is studied by western blotting, real‐time RT‐PCR, and cellular staining. Our results clearly indicate a bifunctional molecular effect of RSV. Both polyphenols are individually able to promote autophagy. Strikingly, when RSV is combined with QCT, it promotes a potent reduction of QCT‐induced autophagy and influences proapoptotic signaling. Conclusion: RSV acts differentially on the autophagic process depending on the cellular energetic state. We further characterize the molecular mechanisms related to this effect, and we observe that AMP‐activated protein kinase (AMPK) phosphorylation, heme oxygenase 1 (HO‐1) downregulation, lysosomal membrane permeabilization (LMP), and Zinc (Zn 2+ ) dynamics could be important modulators of such RSV‐related effects and could globally represent a promising strategy to sensitize cancer cells to QCT treatment. Abstract : Quercetin (QCT), in a combined treatment with an autophagy inhibitor, may be an excellent therapeutic approach to reduce cancer cell proliferation and could be a promising strategy to sensitize cells to QCT treatment. In this sense, several synthetic autophagy inhibitors such as chloroquine or 3‐methyladenine have been shown to be successful for this purpose. In this paper, it is described that resveratrol (RSV) will act differentially on the autophagy process depending on the cellular energetic state.

• Author : David A. Gewirtz,Shawn E. Holt,Steven Grant
• Publisher :Unknown
• Release Date :2007-12-17
• Total pages :599
• ISBN : 9781588295279

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Summary : Provides insight into established practices and research into apoptosis and senescence by examining techniques and research in the fields of cell death pathways, senescence growth arrest, drugs and resistance, DNA damage response, and other topics which still hold mysteries for researchers. This book concludes with established cancer therapies.

• Author : Naomi Whittel
• Publisher :Unknown
• Release Date :2018
• Total pages :320
• ISBN : 9781328897671

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Summary : Based on Nobel Prize-winning research, an easy-to-follow lifestyle plan for losing weight, looking younger, and feeling energized.