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Microrna In Regenerative Medicine

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MicroRNA in Regenerative Medicine

MicroRNA in Regenerative Medicine Book
Author : Chandan K. Sen
Publisher : Elsevier
Release : 2014-11-26
ISBN : 0124058582
Language : En, Es, Fr & De

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Book Description :

This work encapsulates the uses of miRNA across stem cells, developmental biology, tissue injury and tissue regeneration. In particular contributors provide focused coverage of methodologies, intervention and tissue engineering. Regulating virtually all biological processes, the genome’s 1048 encoded microRNAs appear to hold considerable promise for the potential repair and regeneration of tissues and organs in future therapies. In this work, 50 experts address key topics of this fast-emerging field. Concisely summarizing and evaluating key findings emerging from fundamental research into translational application, they point to the current and future significance of clinical research in the miRNA area. Coverage encompasses all major aspects of fundamental stem cell and developmental biology, including the uses of miRNA across repair and regeneration, and special coverage of methodologies and interventions as they point towards organ and tissue engineering Multi-colour text layout with 150 colour figures to illustrate important findings Take home messages encapsulate key lessons throughout text Short chapters offer focused discussion and clear ‘voice’

RNAi and MicroRNA Mediated Gene Regulation in Stem Cells

RNAi and MicroRNA Mediated Gene Regulation in Stem Cells Book
Author : Baohong Zhang,Edmund J. Stellwag
Publisher : Humana
Release : 2010-08-16
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

This cutting-edge text will be a valuable resource for scientists and aspiring graduate students interested in the intersection of RNAi, miRNA, and stem cell molecular biology and exciting areas of research such as regenerative medicine and cancer.

MicroRNAs

MicroRNAs Book
Author : Alain van Mil
Publisher : Unknown
Release : 2012
ISBN : 9789088915208
Language : En, Es, Fr & De

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Book Description :

Download MicroRNAs book written by Alain van Mil, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Transcriptional and Translational Regulation of Stem Cells

Transcriptional and Translational Regulation of Stem Cells Book
Author : Gary Hime,Helen Abud
Publisher : Springer Science & Business Media
Release : 2013-05-22
ISBN : 9400766211
Language : En, Es, Fr & De

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Book Description :

This volume describes the latest findings on transcriptional and translational regulation of stem cells. Both transcriptional activators and repressors have been shown to be crucial for the maintenance of the stem cell state. A key element of stem cell maintenance is repression of differentiation factors or developmental genes – achieved transcriptionally, epigenetically by the Polycomb complex, and post-transcriptionally by RNA-binding proteins and microRNAs. This volume takes two approaches to this topic – (1) illustrating the general principles outlined above through a series of different stem cell examples – embryonic, iPS and adult stem cells, and (2) describing several molecular families that have been shown to have roles in regulation of multiple stem cell populations.

Exosomes Stem Cells and MicroRNA

Exosomes  Stem Cells and MicroRNA Book
Author : Karl L. Mettinger,Pranela Rameshwar,Vinod Kumar
Publisher : Springer
Release : 2018-04-07
ISBN : 3319744704
Language : En, Es, Fr & De

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Book Description :

This volume provides insight into the pivotal roles of stem cells, exosomes and other microvesicles in biofunction and molecular mechanisms and their therapeutic potential in translational nanomedicine. It further highlights evidence from recent studies as to how stem cell derived exosomes and microRNAs may restore and maintain tissue homeostasis, enable cells to recover critical cellular functions and begin repair regeneration. These early studies in animal models of aging also show evidence of improved immune, cardiovascular and cognitive functions as well as improved health span and life span. The use of exosomes from body fluids to define specific biomarkers for various tumors may also clear the path to patient-targeted treatments by developing exosome-derived microRNA based cancer therapeutics. It is essential reading for graduate students, research fellow and biomedical researchers in academia or the pharmaceutical or biotech industries.

Current Perspectives in microRNAs miRNA

Current Perspectives in microRNAs  miRNA  Book
Author : Shao-Yao Ying
Publisher : Springer Science & Business Media
Release : 2008-09-12
ISBN : 1402085338
Language : En, Es, Fr & De

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Book Description :

Nearly 97% of the human genome is the non-coding DNA, which varies from one species to another, and changes in these sequences are frequently noticed to manifest clinical and circumstantial malfunction. Numerous non-protein-coding genes are recently found to encode microRNAs, which are responsible for RNA-mediated gene silencing through RNA interference (RNAi)-like pathways. MicroRNAs (miRNAs), small single-stranded 17–25 nucleotide RNAs capable of interfering with intracellular messenger RNAs (mRNAs) that contain either complete or partial complementarity, are useful for the design of new therapies against cancer polymorphism and viral mutation. Currently over 1000 native miRNA species found in vertebrates and many more new miRNA homologs continue to be identified; however, most of their functions remain to be determined. In this book, many new perspectives of the miRNA research are reviewed and discussed, including their roles in stem cell maintenance, embryonic development, tissue differentiation, adult physiology, disease pathology, cancer research, viral infection, genetic engineering in plants, and utility in cosmetic applications. These new findings may not only provide significant insight into the various mechanisms of miRNAs but also offer a great opportunity in developing new therapeutic interventions.

MicroRNAs and Metabolites in Na ve to Primed Human Embryonic Stem Cell Transition

MicroRNAs and Metabolites in Na  ve to Primed Human Embryonic Stem Cell Transition Book
Author : Hans Henrik Bertil Sperber
Publisher : Unknown
Release : 2014
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

This dissertation research is focused on the small molecules of the cell: metabolites and miRNAs. The purpose is to gain a deeper understanding of how they control the cell by investigating the role of secondary structure during miRNA biogenesis and of the changes that occur in the metabolome during na??ve to primed human embryonic stem cell (hESC) transition. The first chapter of the thesis focuses on miRNA regulation: Through analysis of miRNA secondary structure and miRNA expression levels in cells with different levels of the enzyme Drosha I have found that miRNAs with mismatches in the precursor region of the miRNA, 9-12 nucleotides from the Drosha cutting site show a higher sensitivity to changes in Drosha levels than miRNAs that lack mismatches in said regions. Through mutagenesis experiments I have shown that by altering the miRNA secondary structure its sensitivity to changes in Drosha levels can be changed. This shows how the cell can selectively regulate a group of miRNAs relative to another by changing Drosha expression and may explain the impact of point mutations outside of the seed region of certain miRNAs. miRNA therapies are also being developed, where the small size of miRNAs makes them excellent candidates for gene therapy. The results of this research can be applied to miRNA therapies by increasing the potency of select miRNAs in their target tissues through structural modifications. In cases where the target tissue has different levels of Drosha compared to surrounding tissues (such as in many types of cancer) the miRNA can also be designed to minimize side effects in surrounding healthy tissues. The second chapter of the thesis focuses on the metabolome in human embryonic stem cells: With the use of mass spectrometry combined with gene expression data I have analyzed the metabolome of naïve and primed hESCs. I show that the two developmental stages have distinct profiles in metabolite set up and I have identified pathways that show a change in activity during nave to primed hESC transition. I show that tryptophan degradation is increased in primed cells leading to an accumulation of the tryptophan degradation product kynurenine, which is known to inhibit the antitumor response of the immune system by activting the transcription factor AhR and could be a mechanism which prevents rejection of the recently implanted embryo. I also show that primed hESCs display a decrease in activity of the enzyme NNMT, which uses the metabolite S-adenosyl methionine (SAM) to convert nicotinamide into 1-methyl nicotinamide. The decrease of NNMT activity makes SAM available as a substrate for other methylation mechanisms and increases H3K27me3 methylation. When knocking down NNMT the H3K27me3 marks are increased, supporting the hypothesis that the metabolome regulates the epigenetic landscape during na??ve to primed hESC transition.

Translating Regenerative Medicine to the Clinic

Translating Regenerative Medicine to the Clinic Book
Author : Jeffrey Laurence
Publisher : Academic Press
Release : 2015-09-01
ISBN : 9780128005484
Language : En, Es, Fr & De

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Book Description :

Translating Regenerative Medicine to the Clinic reviews the current methodological tools and experimental approaches used by leading translational researchers, discussing the uses of regenerative medicine for different disease treatment areas, including cardiovascular disease, muscle regeneration, and regeneration of the bone and skin. Pedagogically, the book concentrates on the latest knowledge, laboratory techniques, and experimental approaches used by translational research leaders in this field. It promotes cross-disciplinary communication between the sub-specialties of medicine, but remains unified in theme by emphasizing recent innovations, critical barriers to progress, the new tools that are being used to overcome them, and specific areas of research that require additional study to advance the field as a whole. Volumes in the series include Translating Gene Therapy to the Clinic, Translating Regenerative Medicine to the Clinic, Translating MicroRNAs to the Clinic, Translating Biomarkers to the Clinic, and Translating Epigenetics to the Clinic. Encompasses the latest innovations and tools being used to develop regenerative medicine in the lab and clinic Covers the latest knowledge, laboratory techniques, and experimental approaches used by translational research leaders in this field Contains extensive pedagogical updates aiming to improve the education of translational researchers in this field Provides a transdisciplinary approach that supports cross-fertilization between different sub-specialties of medicine

Stem Cells Regenerative Medicine

Stem Cells   Regenerative Medicine Book
Author : Krishnarao Appasani,Raghu K. Appasani
Publisher : Springer Science & Business Media
Release : 2010-11-01
ISBN : 9781607618607
Language : En, Es, Fr & De

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Book Description :

Defined as, “The science about the development of an embryo from the fertilization of the ovum to the fetus stage,” embryology has been a mainstay at universities throughout the world for many years. Throughout the last century, embryology became overshadowed by experimental-based genetics and cell biology, transforming the field into developmental biology, which replaced embryology in Biology departments in many universities. Major contributions in this young century in the fields of molecular biology, biochemistry and genomics were integrated with both embryology and developmental biology to provide an understanding of the molecular portrait of a “development cell.” That new integrated approach is known as stem-cell biology; it is an understanding of the embryology and development together at the molecular level using engineering, imaging and cell culture principles, and it is at the heart of this seminal book. Stem Cells and Regenerative Medicine: From Molecular Embryology to Tissue Engineering is completely devoted to the basic developmental, cellular and molecular biological aspects of stem cells as well as their clinical applications in tissue engineering and regenerative medicine. It focuses on the basic biology of embryonic and cancer cells plus their key involvement in self-renewal, muscle repair, epigenetic processes, and therapeutic applications. In addition, it covers other key relevant topics such as nuclear reprogramming induced pluripotency and stem cell culture techniques using novel biomaterials. A thorough introduction to stem-cell biology, this reference is aimed at graduate students, post-docs, and professors as well as executives and scientists in biotech and pharmaceutical companies.

MicroRNAs in Medicine

MicroRNAs in Medicine Book
Author : Charles H. Lawrie
Publisher : John Wiley & Sons
Release : 2013-10-30
ISBN : 1118300343
Language : En, Es, Fr & De

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Book Description :

MicroRNAs in Medicine provides an access point intothe current literature on microRNA for both scientists andclinicians, with an up-to-date look at what is happening in theemerging field of microRNAs and their relevance to medicine. Eachchapter is a comprehensive review, with descriptions of the latestmicroRNA research written by international leaders in their field.Opening with an introduction to what microRNAs are and how theyfunction, the book goes on to explore the role of microRNAs innormal physiological functions, infectious diseases, non-infectiousdiseases, cancer, circulating microRNAs as non-invasive biomarkers,and finally their potential as novel therapeutics. Including background information on the field as well as reviewsof the latest research breakthroughs, MicroRNAs inMedicine is a one-stop source of information to satisfythe specialists and non-specialists alike, appealing to students,researchers, and clinicians interested in understanding thepotential of microRNAs in medicine and research.

Alterations of Epigenetics and MicroRNAs in Cancer and Cancer Stem Cell

Alterations of Epigenetics and MicroRNAs in Cancer and Cancer Stem Cell Book
Author : Yoshimasa Saito
Publisher : Frontiers E-books
Release : 2014-11-10
ISBN : 2889193454
Language : En, Es, Fr & De

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Book Description :

Studies have shown that alterations of epigenetics and microRNAs (miRNAs) play critical roles in the initiation and progression of human cancer. Epigenetic silencing of tumor suppressor genes in cancer cells is generally mediated by DNA hypermethylation of CpG island promoter and histone modification such as methylation of histone H3 lysine 9 (H3K9) and tri-methylation of H3K27. MiRNAs are small non-coding RNAs that regulate expression of various target genes. Specific miRNAs are aberrantly expressed and play roles as tumor suppressors or oncogenes during carcinogenesis. Important tumor suppressor miRNAs are silenced by epigenetic alterations, resulting in activation of target oncogenes in human malignancies. Stem cells have the ability to perpetuate themselves through self-renewal and to generate mature cells of various tissues through differentiation. Accumulating evidence suggests that a subpopulation of cancer cells with distinct stem-like properties is responsible for tumor initiation, invasive growth, and metastasis formation, which is defined as cancer stem cells. Cancer stem cells are considered to be resistant to conventional chemotherapy and radiation therapy, suggesting that these cells are important targets of cancer therapy. DNA methylation, histone modification and miRNAs may be deeply involved in stem-like properties in cancer cells. Restoring the expression of tumor suppressor genes and miRNAs by chromatin modifying drugs may be a promising therapeutic approach for cancer stem cells. In this Research Topic, we discuss about alterations of epigenetics and miRNAs in cancer and cancer stem cell and understand the molecular mechanism underlying the formation of cancer stem cell, which may provide a novel insight for treatment of refractory cancer.

Investigation of Stem Cell specific MicroRNA Expression as Potential Stem Cell Regulators in Rabbit Embryos and Embryonic Stem Cells

Investigation of Stem Cell specific MicroRNA Expression as Potential Stem Cell Regulators  in Rabbit Embryos and Embryonic Stem Cells Book
Author : Pouneh Maraghechi
Publisher : Unknown
Release : 2013
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Investigation of Stem Cell specific MicroRNA Expression as Potential Stem Cell Regulators in Rabbit Embryos and Embryonic Stem Cells book written by Pouneh Maraghechi, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Regulation of Stem Cell Self renewal by MicroRNAs

Regulation of Stem Cell Self renewal by MicroRNAs Book
Author : Christopher Paul Arnold
Publisher : Unknown
Release : 2012
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Stem cell self-renewal is dynamically regulated in response to extrinsic stimuli, but the intrinsic mechanisms that mediate the effects of these stimuli remain elusive. Emerging evidence suggests that miRNAs, an abundant class of ~22-nt small regulatory RNAs, play key roles in controlling the post-transcriptional genetic programs in stem and progenitor cells. We systematically examined miRNA expression profiles in various normal and aberrant adult tissue-specific stem and progenitor cells. Delineation of miRNAs whose expression correlated with changes in the self-renewal properties during normal development and as the result of mutant perturbations permitted the identification of miRNAs that marked stem to progenitor transition, termed SPT-miRNAs. Expression of SPT-miRNAs correlated with the exit from a self-renewing state as well as reduced self-renewal capacity in various normal and leukemia stem cells, suggesting that they may play a role in post-transcriptional gene silencing of key mediators of stem cell self-renewal. Consistent with this hypothesis, premature expression of a subset of these miRNAs could diminish the reconstitution potential of hematopoietic stem cells (HSCs) and the self-renewal of embryonic stem cells (ESCs). Furthermore, SPT-miRNAs targeted genes necessary for the self-renewal of HSCs, suggesting that up-regulation of these miRNAs permitted the efficient silencing of self-renewal programs during the stem to progenitor transition. Given the functional overlap of SPT-miRNAs in both embryonic and adult stem cells, we hypothesized that the expression of some SPT-miRNAs may be actively repressed by extrinsic signaling cues in stem cells at multiple developmental stages to potentiate their self-renewal. By subjecting ESCs to various culture conditions that diminished their self-renewal efficiency, we observed an up-regulation of a subset of SPT-miRNAs; in particular, members of the miR-181 family. Ectopic expression of this miRNA reduced ESC self-renewal whereas its deletion augmented ESC self-renewal in serum-free medium. These changes in self-renewal were attributable to simultaneous modulation of ESC proliferation and lineage commitment via target interactions with Lin28A, Spry4, and Dusp6. Finally, we found that the BMP-signaling pathway, necessary for the efficient self-renewal of ESCs, played a key role in the suppression of miR-181a. Collectively, these results reveal how extrinsic signaling cues mediate the quantitative post-transcriptional regulation of stem cell self-renewal programs via the modulation of miRNAs. Our study demonstrated one approach to identify and investigate the role of intrinsic regulators and provided novel insight into how to uncover the intrinsic regulators of stem cell self-renewal with implications on manipulation of stem cell expansion ex vivo.

Frontiers in Stem Cell and Regenerative Medicine Research Volume 9

Frontiers in Stem Cell and Regenerative Medicine Research  Volume 9 Book
Author : Atta-ur-Rahman ,Shazia Anjum
Publisher : Bentham Science Publishers
Release : 2020-05-05
ISBN : 1681087634
Language : En, Es, Fr & De

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Book Description :

Stem cell and regenerative medicine research is an important area of clinical research which promises to change the face of medicine as it will be practiced in the years to come. Challenges in the 21st century to combat diseases such as cancer, Alzheimer’s disease and retinal disorders, among others, may well be addressed employing stem cell therapies and tissue regeneration techniques. Frontiers in Stem Cell and Regenerative Medicine Research is essential reading for researchers seeking updates in stem cell therapeutics and regenerative medicine. This volume includes current literature on a variety of topics: -the utility of exogenous and endogenous neural stem cells in spinal cord injury -somatic cells for human induced pluripotent stem cells (iPSCs) -reactive oxygen species (ROS) mediated cellular signaling for stem cell differentiation -the therapeutic potential of microRNAs in cardiac diseases -stem cell therapy for the treatment of malaria

Regenerative Medicine for Degenerative Muscle Diseases

Regenerative Medicine for Degenerative Muscle Diseases Book
Author : Martin K. Childers
Publisher : Humana Press
Release : 2015-12-19
ISBN : 1493932284
Language : En, Es, Fr & De

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Book Description :

This book compiles and explores cutting-edge research in degenerative skeletal disorders, such as Duchenne muscular dystrophy and congenital myopathy, and new stem-cell based therapies and gene replacement therapy. Twelve expertly-authored chapters navigate the nuances of these treatments in an array of contexts and biological systems. The topics covered include: How are urine cells from a patient with Duchenne muscular dystrophy transformed into beating heart cells? What can reprogrammed cells tell us about heart muscle failure? What do gene mutations mean for those born with a muscle disease? How are manufacturing methods applied to human stem cells? Does therapeutic exercise benefit those patients who receive engineered limb muscle? Is there practical advice about nutrition to enhance muscle function for the Duchenne patient? Can microRNAs be useful to regenerate diseased muscle? Regenerative Medicine for Degenerative Muscle Diseases is ideal for scientists and clinicians from varying disciplines in genetics, cell biology, virology, cell-based manufacturing, rehabilitation medicine, nutrition, veterinary medicine and neurosurgery. The reader will see how transformative changes occur in medicine that can powerfully impact the future for patients suffering from inherited disorders affecting muscles of the body, including the heart.

The Role of Mirnas and Pirnas in Planarian Regeneration

The Role of Mirnas and Pirnas in Planarian Regeneration Book
Author : Magda Maria Smielewska
Publisher : Unknown
Release : 2008
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Planarians are bilaterally symmetric metazoans that have the incredible ability to completely regenerate their entire body from a piece as small as 1/279th of a whole animal. This amazing regenerative capacity requires a population of stem cells called neoblasts. Several genes have been identified that are essential for regeneration in the planarian Schmidtea mediterranea. Conservation of most of these genes across the animal kingdom suggests that planarians are an excellent model system to study stem cell biology. MicroRNAs are small non-coding RNA molecules 21-24 nt in length that function by binding to the 3'UTRs of mRNAs where they prevent translation of the encoded protein or promote mRNA degradation. In other species, miRNAs have been shown to be involved in processes as diverse as fat metabolism, hematopoiesis, apoptosis, and the cell cycle. To begin studying the role of miRNAs in regeneration and stem cell function in planarians, we set out to identify miRNAs. During our experiments we sequenced over 2,400,000 small RNAs, which allowed us to identify 104 miRNA encoding loci in the S. Mediterranea genome. Our analysis of sequences from intact, regenerating, and irradiated planarians, has revealed dynamic changes in miRNA expression patterns. In particular, we found that members of the let-7 family of miRNAs appear to be expressed in neoblasts and therefore might be important regulators of stem cell function in planarians. Our sequencing efforts have also identified a second class of small RNAs in planarians called piRNAs. Intriguingly, in contrast to what is observed in other metazoans, in planarians, piRNA expression is not restricted to the germline, but rather appears to be specific to neoblasts. Therefore, piRNAs appear to be regulators of stem cell maintenance and/or self-renewal in planarians. To further study the function of miRNAs in regeneration, we have cloned cDNAs encoding the miRNA synthesis machinery. Depletion of these proteins by RNA interference has revealed that a subset of these proteins are required for regeneration, homeostasis and proper miRNA synthesis. These experiments lay the groundwork for functional studies aimed at clarifying the role of miRNAs and piRNAs in regeneration, cell lineage decisions, and basic stem cell biology.

Stem Cells and Cardiac Regeneration

Stem Cells and Cardiac Regeneration Book
Author : Rosalinda Madonna
Publisher : Springer
Release : 2015-12-18
ISBN : 3319254278
Language : En, Es, Fr & De

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Book Description :

This book provides an update of recent advances in the basic and clinical applications of cell-based therapies for myocardial repair and regeneration in ischemic heart disease (IHD) and heart failure (HF). The first sections of the book illuminate basic aspects of stem cells such as definitions, isolation criteria and characterization of embryonic and adult stem cells, as well as pluripotent stem cells and tissue specific progenitor and stem cells. In the following section, the text examines the role of critical regulators of stem cell differentiation in myocardial regeneration, that include circadian rhythyms, microRNAs, epigenetics, microvescicles, and exosomes. The text concludes with a review of the use of stem/progenitor cells in cardiac regeneration and discuss current controversies, unresolved issues, challenges, and future directions. Stem Cells and Cardiac Regeneration is addressed to a wide audience consisting of cardiologists, clinicians, and research scientists, who will learn new concepts in cardiovascular regeneration and repair with special focus on molecular mechanisms and therapeutic potential for cardiovascular regeneration.

Regenerative Medicine from Protocol to Patient

Regenerative Medicine   from Protocol to Patient Book
Author : Gustav Steinhoff
Publisher : Springer
Release : 2016-04-25
ISBN : 3319275836
Language : En, Es, Fr & De

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Book Description :

Regenerative medicine is the main field of groundbreaking medical development and therapy using knowledge from developmental and stem cell biology, as well as advanced molecular and cellular techniques. This collection of volumes on Regenerative Medicine: From Protocol to Patient, aims to explain the scientific knowledge and emerging technology, as well as the clinical application in different organ systems and diseases. International leading experts from all over the world describe the latest scientific and clinical knowledge of the field of regenerative medicine. The process of translating science of laboratory protocols into therapies is explained in sections on regulatory, ethical and industrial issues. This collection is organized into five volumes: (1) Biology of Tissue Regeneration, (2) Stem Cell Science and Technology, (3) Tissue Engineering, Biomaterials and Nanotechnology, (4) Regenerative Therapies I, and (5) Regenerative Therapies II. The textbook gives the student, the researcher, the health care professional, the physician and the patient a complete survey on the current scientific basis, therapeutical protocols, clinical translation and practiced therapies in regenerative medicine. Volume 1 contains eleven chapters addressing the latest basic science knowledge on the “Biology of Tissue Regeneration”. The principles of cell regeneration control by extracellular matrix and the biology of stem cell niches are explained. Depicted are the principles of molecular mechanisms controlling asymmetric cell division, stem cell differentiation, developmental and regenerative biology, epigenetic and genetic control as well as mathematical modelling for cell fate prediction. Regenerative biology of stem cells in the central nervous and cardiovascular systems leading to complex tissue regeneration in the model species axolotl and zebrafish, as well as the impact of immune signalling on nuclear reprogramming are outlined. These up to date accounts gives the readers advanced insights into the biological principles of the regenerative processes in stem cells, tissues and organisms.

Modulation of Intestinal Micrornas by a Chemoprotective Diet

Modulation of Intestinal Micrornas by a Chemoprotective Diet Book
Author : Manasvi Shailesh Shah
Publisher : Unknown
Release : 2013
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

We have hypothesized that dietary modulation of intestinal miRNA expression may contribute to the chemoprotective effects of nutritional bioactives (fish oil and pectin). Using a rat colon carcinogen model, we determined miRNAs-let-7d, miR-15b, miR-107, miR-191 and miR-324-5p were modulated by fish oil + pectin. We also demonstrated that BACE1 and PTEN are targets of miR-107 and miR-21, respectively. To further elucidate the biological effects of diet and carcinogen on miRNAs, we integrated global miRNAs, total and polysomal gene expression datasets obtained from the above mentioned study and used four computational approaches. We demonstrated that polysomal profiling is tightly related to microRNA changes when compared with total mRNA profiling. In addition, diet and carcinogen exposure modulated a number of microRNAs and complementary gene expression analyses showed that oncogenic PTK2B, PDE4B, and TCF4 were suppressed by the chemoprotective diet at both the mRNA and protein levels. To determine the function of select diet and colon carcinogen modulated miRNAs and to validate their targets, we carried out a series of loss and gain of function experiments along with luciferase reporter assays. We verified that PDE4B and TCF4 are direct targets of miR-26b and miR-203, respectively. PTK2B was determined to be an indirect target of miR-19b. In addition, microRNA physiological function was assessed by examining effects on apoptosis and cell proliferation. To better understand how the colonic stem cell population responds to environmental factors such as diet and carcinogen, we investigated the chemoprotective effects of dietary agents on miRNAs in colonic stem cells obtained from Lgr5-EGFP-IRES-creER^T2 knock in mice injected with AOM. We demonstrated that based on relative expression of miR-125a-5p, miR-190b and miR-191 in stem cells vs. daughter cells and differentiated cells, these miRNAs may be stem cell specific miRNAs. We also identified miR-21 to be significantly reduced in stem cells compared to differentiated cells and selectively modulated by these dietary agents in stem cells. In summary, our results indicate for the first time that fish oil plus pectin protect against colon tumorigenesis in part by modulating a subset of miRNAs and their target genes (mRNAs) implicated in the regulation of the colon stem cell niche and tumor development. The electronic version of this dissertation is accessible from http://hdl.handle.net/1969.1/148169

Cancer Research

Cancer Research Book
Author : Anonim
Publisher : Unknown
Release : 2009-05
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Cancer Research book written by , available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.