Genomic and Epigenomic Biomarkers of Toxicology and Disease

Genomic and Epigenomic Biomarkers of Toxicology and Disease
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Genomic and Epigenomic Biomarkers of Toxicology and Disease The latest developments in biomarker research applicable to toxicology and medicine Research on genomic and epigenomic biomarkers is developing rapidly with cutting-edge studies scattered throughout the academic literature, making the status of ongoing scientific activity in this area difficult to ascertain. Genomic and Epigenomic Biomarkers of Toxicology and Disease: Clinical and Therapeutic Actions delivers a comprehensive and authoritative compilation of up-to-date developments in the application of genomic and epigenomic biomarkers to toxicology, disease prevention, cancer detection, therapeutics, gene therapy, and other areas. With contributions from a collection of internationally recognized investigators, this edited volume offers unique insights into current trends and future directions of research in the discussed areas. Combining state-of-the-art information on genomic and epigenomic biomarkers from a range of specialists from around the world, this monograph includes: A thorough introduction to microRNAs as non-invasive biomarkers of toxicity and chemical hazard Comprehensive explorations of extracellular vesicle-associated miRNAs as toxic biomarkers, as well as transcriptomic applications in toxicology and medicine Practical discussions of circulating miRNAs as biomarkers of metal exposure, as well as microRNAs biomarkers of malignant mesothelioma In-depth examinations of the role of noncoding RNAs in innate immune responses perturbed by environmental arsenic with a focus on microRNAs Perfect for researchers, toxicologists, risk assessors, and regulators, Genomic and Epigenomic Biomarkers of Toxicology and Disease: Clinical and Therapeutic Actions will also earn a place in the libraries of graduate students with an interest in biomarkers, toxicology, agriculture, or the environment.

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Группа авторов. Genomic and Epigenomic Biomarkers of Toxicology and Disease

Genomic and Epigenomic Biomarkers of Toxicology and Disease. Clinical and Therapeutic Actions

Contents

List of Illustrations

List of Tables

Guide

Pages

Dedication

Preface

Acknowledgements

List of Contributors

1 Genomic and Epigenomic Biomarkers for Predictive Toxicity and Disease

Toxicity Testing in the Twenty-First Century

Biomarkers

Genomic Biomarkers

Epigenomic Biomarkers

MicroRNAs

Circular RNAs

The Need for a Book on Genomic and Epigenomic Biomarkers for Predictive Toxicity and Disease

References

2 MicroRNAs as Non-invasive Biomarkers of Toxicity and Chemical Hazard Genomic and Epigenomic Biomarkers of Toxicology and Disease

Introduction

Mechanisms that Contribute to Extracellular miRNA Release

Packaging into Vesicles and Mechanisms of Release

Biological Interpretations Due to Mechanisms of Release

MicroRNAs as Bioindicators of Toxicity and Disease

Application

Challenges and Future Focus

Conclusions

Acknowledgements

References

3 EV (Extracellular Vesicle)-associated miRNAs as Biomarkers of Toxicity

Introduction

The Classification of Extracellular Vesicles (EVs)

Components of Exosomes (EVs) RNAs

Proteins

Physiological and Cellular Functions of EVs

Cancer Biomarkers

Toxicology Biomarkers

Isolation and Characterization of EVs from Mouse Blood

Carbon Tetrachloride (CCl4) Administration and Histology

Identification of Differentially Expressed miRNAs by RNA-Seq

Conclusion

Acknowledgments

Competing Interests

Funding

References

4 Circulating miRNAs as Biomarkers of Toxic Heavy Metal Exposure

Metals and the Focus of This Chapter

Exposure to Metals

Biomarkers

Biomarkers of Heavy Metal Exposure

miRNA Biogenesis

Circulating miRNAs as Biomarkers for Disease

Circulating miRNAs Associated with Arsenic Exposure

Circulating miRNAs Associated with Lead Exposure

Circulating miRNAs Associated with Mercury Exposure

Circulating miRNAs Associated with Cadmium Exposure

Circulating miRNAs Associated with Chromium Exposure

Circulating miRNAs Associated with Mixed Metals Exposure

Summary of Potential Circulating miRNA Biomarkers for Heavy Metals

Future Avenues of Research

Techniques and Challenges for Identifying Circulating miRNAs

Acknowledgement

References

5 MicroRNA Biomarkers of Malignant Mesothelioma

Methods for Detecting the Expression of miRNAs

Early Screening for Malignant Mesothelioma

Diagnosis of Malignant Mesothelioma

Differential Expression of miRNAs in Cancer Tissues

Differential Expression of MicroRNAs in Serum and Plasma

Differential Expression of miRNAs in Pleural Effusion

MicroRNAs Associated with Malignant Mesothelioma Tissue Subtypes

Differential Diagnosis

MicroRNAs Related to the Occurrence and Development of Mesothelioma

MicroRNAs Related to Cell Cycle Regulation

MicroRNAs Related to Proliferation and Clone Formation

MicroRNAs Associated with Migration and Invasion

Apoptosis-related miRNAs

Inhibition of miRNAs Associated with Explant Tumor

Exosomal miRNA as a Target for Malignant Mesothelioma

MicroRNAs Related to Prognosis of Malignant Mesothelioma

References

6 Role of Non-coding RNAs in Innate Immune Responses Perturbed by Environmental Arsenic Exposure

Introduction

The Innate Immune System

Negative Impacts of Arsenic on Human Health

Negative Impacts of Arsenic on the Immune Function

The Zebrafish Model for Toxicological Responses to Arsenic

The Zebrafish Model of Innate Immune Responses

Role of Non-coding RNAS in Innate Immunity. Overview of Non-coding RNAs

MiRNAs Regulate Response to Injury and Infection Involving Multiple Cell Types

MiRNAs Regulate Macrophage Function

MiRNAs Regulate Neutrophil Function

The Expression of Non-coding RNAs Altered by Arsenic

Discussion

Gene-by-Environment Interactions

Functional Studies of Non-coding RNAs Using the Zebrafish Model

Future Studies on Gene-by-Environment Interactions

Acknowledgments

References

7 Transcriptomics Applications in Toxicology and Medicine

Introduction

Transcriptomics: Technical Aspects

Superior Sensitivity of Gene Expression Changes to Detect Target Organ Toxicity

Silica Exposure and Toxicity

In Vitro Cell Culture Studies

In Vivo Animal Studies

Lung Response to Crystalline Silica Exposure in Rats

Lung Gene Expression Changes in Response to Crystalline Silica Exposure

Blood Gene Expression Changes in Response to Crystalline Silica Exposure

Blood Gene Expression Signature to Predict/Detect Silica Exposure/Lung Toxicity

Molecular Mechanisms of Lung Response to Silica Exposure

Crystalline Silica and Lung Fibrosis

Transcriptomics and Alzeimer’s Disease

References

8 Network Biology for Biomarker Discovery and Therapy in Cancer

Introduction

Categories of Graphs in Biology

Molecular Networks and Their Role in Cancer Biomarker Discovery

Protein–Protein Interaction Network

Co-expression Network

Gene Transcriptional Regulatory Networks

Metabolic Network

Network Medicine and Drug Design

Conclusion

References

9 Epigenetic Biomarkers Link to Maternal Exposure and Offspring Health Outcomes

Introduction

Alterations in the Epigenetic Markers of Pregnancy or Birth Outcomes and Childhood Disease

Preeclampsia

Small for Gestational Age and Preterm Birth

Allergic Diseases

Metabolic Syndrome

Neurodevelopmental Disorders

Exposure to Prenatal Insults and Epigenetic Changes

Air Pollution and Smoking

Metals

Organic Pollutants

Maternal Diet

New Challenges and Future Directions

References

10 The Role of Dynamic Epigenetic Changes in Modulating Homeostasis after Exposure to Low-dose Environmental Chemicals

Introduction

Dynamic Epigenetic Changes after Environmental Exposure

DNA Methylation as a Potential Epigenetic Memory of Past Exposure Events

Histone Heterochromatin Markers and Their Modulators, Which Reshape the Epigenetic Landscape in Response to Past Exposure Events

The Epigenetic Regulation of Homeostasis. The Epigenetic Regulation of Metabolic Homeostasis

A Major Hypothesis in the Histone Acetylation Regulation of Metabolism

Histone Methylation-Regulated Metabolic Enzymes are Cell Type-Dependent

DNA Methylation Connects the Epigenome in the Nucleus and the Epigenome in Mitochondria

Epigenetic Regulation of Autophagy

Epigenetic Regulation of Calcium Signaling

Epigenetic Alterations Enriched in Homeostasis Pathways as a Potential Biomarker after Environmental Exposure

Conclusions

References

11 Emerging Non-invasive Molecular Biomarkers for Early Cancer Detection

Introduction

Conventional Methods of Early Cancer Diagnosis

Emerging Non-invasive Cancer Biomarkers. Diagnostic ctDNA Markers

MiRNAs as Biomarkers for Early Cancer Diagnosis

Exosomes as Cancer Biomarkers

Concluding Remarks

References

12 Aberrant DNA Methylation of Tumor Suppressor Genes and Oncogenes as Cancer Biomarkers

Introduction

Aberrant DNA Methylation of Tumor Suppressor Genes. P53

RASSF1A

Cadherin-1

Aberrant DNA Methylation of Oncogenes. Ras

ONECUT2

BORIS

Future Perspectives

References

13 SMYD Protein Family as Promising Biomarkers for Cancer Diagnosis and Prognosis

Introduction

SMYD Proteins as Cancer Biomarkers. Genetic Alterations as Biomarkers

Abnormal Expression as Biomarkers

SMYD Protein-mediated Lysine Methylation as a Cancer Biomarker. Functional Impacts of Protein Lysine Methylation

Histone Lysine Methylation as a Biomarker

Non-histone Lysine Methylation as a Biomarker

The RTK-RAS Signaling Pathway

Wnt Signaling Pathway

Cell Cycle Regulation

Concluding Remarks

References

14 Toward Precision Medicine Epigenetic Alterations in Human Melanoma

Introduction

Epigenetic Alterations in Melanoma

DNA Methylation

Histone Modifications

Non-coding RNAs as Epigenetic Regulators

Pathogenesis and Molecular Biology of Melanoma

Current Therapeutic Approaches

Therapeutic Implications of Epigenetic Changes in Melanoma

Conclusion

References

15 Currents Trends and Future Perspectives in Our Epigenetic Signatures What a Diet Can Trigger

How Epigenetics Influences Life: Short Overview

Diet-induced Epigenetic Alterations: Transgenerational Effects and Early Life Nutrition

Exposure to Chemicals through Food Chain

Nutritional Genomic Approaches in Cancers

Epigenetics and Prebiotics, Probiotics, and Postbiotics

Conclusion and Future Perspectives

References

16 Genetic and Epigenetic Biomarkers of Organophosphate Compounds, Dialkyl Phosphate Exposure, and Their Relation to Biological Effects

Introduction

Organophosphate Compounds

Dialkyl Phosphates

Toxicokinetics

OP Exposure

Regulations

OP Biomarkers

DAPs

Cholinesterases

Adducts

OP Toxic Effects

Genotoxicity of OP Compounds

Suggested Mechanisms. Clastogenicity

Aneuploidy

Biomarkers of Genotoxicity

Epigenetic Effects of OP Compounds

Suggested Mechanisms. DNA Methylation

Histone Modification

Adduct Formation

Potential Epigenetic Biomarkers

Concluding Remarks

References

17 Genetic, Epigenetic, and Anatomical Factors in Agenesis and Development of Female Reproductive Tract

Introduction

The Dysregulation of Genomic Factors in the Development of the Müllerian Duct Causes MRKH Syndrome

The Relationship of Epigenomic and Anatomical Factors with MRKH Syndrome

Estrogen Receptors in the Developing Uterus Are Irreversibly Involved in Uterine Function and Disease

Conclusion

Acknowledgment

References

18 Cause or Consequence Epigenomic DNA Methylation Changes in Arsenic-Mediated in Vitro Transformation of Human Prostate Cells

Introduction

Materials and Methods. Cells and Cell Culture

RNA-seq and Differential Expression

BisDNA-seq

Validation of Methylated Sequences by Roche454 Sequencing

Results. Gene Expression by RNA-seq

DNA Base-pair Methylation and Methylation Clusters

Proximity of Hg19 DMCs to the Gene Structure

Correlation of DNA Methylation and Gene Expression

Discussion

Acknowledgment

Disclaimer

References

19 Epigenetic Regulation of Sex Determination and Toxicity in Non-mammalian Vertebrates

Introduction

DNA Methylation

Histone Modifications

Non-coding RNAs

Sex Determinig Cascades in Mammals and Non-mammals

Cyp19a1

Dmrt1

Sex Determination and Reversal in Fish. Sex Determination in Chondricthyan Fish

Diverse Sex Determination Mechanisms in Teleost Fish

Modes of Sex Determination and Reversal among Teleost Species

Genetic Sex Determination

Environmental Sex Determination

Epigenetic Regulation of Sex Determination and Reversal in Gonochorists

Epigenetic Regulation of Sex Reversal in Sequential Hermaphrodites

Primordial Germ Cell Maintenance and Its Effect on Sex Determination

Epigenetic Regulation of Sex Determination in Amphibians and Reptiles. Sex Determination and Reversal in Amphibians

Sex Determination in Reptiles

Epigenetic Regulation of Sex Determination in Reptiles

Differential Methylation of Genomes by Incubation Temperatures

Epigenetic Regulation of Sex Determination in Alligators and Turtles

Comparison between GSD and TSD Species

Epigenetic Machinery and Sex Reversal in an Australian Lizard

Epigenetic Regulation of Sex Determination in Birds. Sex Determination and Gonadal Differentiation in Birds

Hypotheses Regarding Sex Determination in Birds

Sex Steroids and Avian Sex Differentiation

The Epigenetic Regulation of Avian Sex Determination

DNA Methylation and Histone Modifications

Regulation of Dmrt1 Expression by Non-coding RNAs

Possible Effects of Epigenetic Toxicants on Sex Determination of Non-mammalian Vertebrates. Epigenetic Toxicants and Their Implications for Non-mammalian Vertebrates

Case Studies

Possible Application of Non-mammalian Vertebrates as Biomarkers for Epigenetic Toxicants

Acknowledgment

References

20 Characterization of Genomic and Epigenomic Biomarkers of Nanoparticle Toxicity Using the Zebrafish Model System

Zebrafish: A Popular Experimental Animal Model

The Zebrafish Genome. Important Features of the Zebrafish Genome

Zebrafish and “-omics” Approaches

General Molecular Determinants and Genomic and Epigenomic Biomarkers of Nanoparticle Toxicity in Zebrafish

Genome and Genetic Biomarkers of Nanoparticle Toxicity Associated with Different Systems in Zebrafish

Neuronal Lineage Genetic Biomarkers of Nanoparticle Toxicity

Immune Lineage Genetic Biomarkers Associated with Nanoparticle Toxicity

Genetic Biomarkers of Nanoparticle Toxicity Associated with Reproductive Health

Genetic Biomarkers of Nanoparticle Toxicity Associated with Embryonic Development

Future Directions of Zebrafish Research for Informing Genomic and Epigenomic Biomarkers of Nanoparticle Toxicity through Novel Genetic Models and Integrated -omic Approaches to Clinical and Therapeutic Action

Conclusions

Funding

References

Index

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Edited by

Saura C. Sahu

.....

Alexandra N. Nail

Department of Pharmacology and

.....

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