Biomedical Research, Medicine, and Disease

Description

Biomedical research is the first step towards the creation of new medications and treatments that help to manage different types of health conditions and diseases. The prevention and cure of diseases would be practically impossible without such type of research. Although the drug discovery and development processes are far too costly, time-consuming, prone to failure, and have low success rate, today the term "translational research or medicine" seems to have become trendy, yet it is insufficient. The present book is a sincere attempt by dedicated researchers to convey the importance of translational biomedical research, medicine, and disease, primarily, basic and clinical difficulties in the translation of diagnostic measures, pharmaceutical advances, biomarkers, diagnostics, and therapeutics. This book is meant for researchers, scientists, healthcare professionals, industry, innovators, and students of biomedical sciences, as well as for those involved in the basic sciences, biochemistry, biotechnology, biophysics, and life sciences in general. The volume comprehensively covers i. Emerging technologies for health care, ii. Various aspects of biomedical research toward understanding of pathophysiology of the diseases, iii. Advances in improvement in diagnostic procedures and therapeutic tools, iv. The fundamental role of biomedical research in the development of new medicinal products. Cover Half Title Title Page Copyright Page Table of Contents Preface Acknowledgments Editor Biographies List of Contributors Section I Advancement in Techniques in Biomedical Science 1 Recent Advancements in Biomedical Sciences and Their Healthcare Applications 1.1 Introduction 1.2 AI and ML in Disease Diagnostics and Prediction 1.3 AI in Drug Development 1.3.1 AI in Drug Design 1.3.2 AI in Polypharmacology 1.3.3 AI in Chemical Synthesis 1.3.4 AI in Drug Repurposing 1.3.5 AI in Drug Screening 1.4 Conclusion References 2 Nanotechnology in Medicine: A Promising Future 2.1 Introduction 2.2 Reviewing Nanotechnology in Biomedical Applications 2.2.1 PillCam 2.2.2 Drug Delivery 2.2.3 Biomarkers 2.2.4 Microbots 2.3 Cancer Detection and Treatment 2.3.1 Multiplexing and Immunoassays 2.4 Extracellular Cancer Biomarkers 2.4.1 Detection By MRNA and MicroRNA 2.4.2 DNA Methylation Detection 2.5 Nanotechnology for In Vivo Imaging 2.5.1 Challenges in Clinical Translation 2.6 Discussion 2.7 Conclusion References 3 How Flow Cytometers Work: An Introduction for Biomedical Scientists 3.1 Introduction 3.2 Instrument Fluidics 3.2.1 Flow Cells and Hydrodynamic Focusing 3.2.2 Instrument Fluidics 3.3 Instrument Optics 3.3.1 Lasers, Laser Optics, and the Laser Intercept 3.3.2 Light Collection and Detectors 3.3.3 Detection Optics 3.4 Electronics, Computers, and Software 3.5 Flow Cytometric Data Acquisition and Analysis 3.5.1 Forward and Side Scatter 3.5.2 Fluorescence Detection and Multicolor Analysis 3.6 The Limits of Multicolor Flow Cytometry 3.7 Cell Sorting 3.8 Other Applications for Flow Cytometry References 4 Multicolor Flow Cytometry and Panel Design 4.1 Introduction 4.2 The Basics: Light, Fluorochromes, and Fluorescence 4.3 Spectral Spillover and Compensation 4.3.1 Practical Rules for Good Compensation 4.3.2 Sources of Spectral Spillover 4.4 Resolution and Background: Distinguishing Positive From Negative 4.5 Elements to Consider When Designing a Multicolor Panel 4.6 Multicolor Panel Design Summary 4.6.1 Experimental Controls 4.7 Conclusions References 5 Digital Watermarking Techniques for Medical Image Security Using the Fuzzy Analytical Hierarchy Process 5.1 Introduction 5.2 Fuzzy Sets 5.2.1 Linguistic Variable 5.2.2 Fuzzy Number 5.2.3 Fuzzy AHP 5.3 The Empirical Framework 5.3.1 Criteria Selection 5.3.2 Results Analysis 5.4 Empirical Analysis 5.4.1 Fuzzy Pair-Wise Matrix 5.5 Conclusion Acknowledgement References 6 Limbal Stem Cell Deficiency: Concurrent Approaches and Scope of Regenerative Stem Cell Therapy and Blood Derivatives 6.1 Introduction 6.2 The Limbus and the Limbal Stem Cell Niche 6.2.1 Structural Anatomy 6.2.2 Microenvironment (ECM) and Putative Biomarkers 6.3 Etiology 6.4 Common Surgical Methods for Treating LSCD 6.4.1 Mechanical Debridement/Keratectomy and Phototherapeutic Keratectomy 6.4.2 Amniotic Membrane Transplantation 6.4.3 Autologous and Allograft Limbal Stem Cell Transplantation 6.4.4 Cultivated Limbal Epithelial Stem Cells 6.5 Regenerative Cell-Based Therapy By Stem Cells: The Emerging Hope 6.5.1 Dental Pulp Stem Cells 6.5.2 Hair Follicle Stem Cells 6.5.3 Adipose-Derived Stem Cells and Conditioned Medium 6.5.4 Embryonic Stem Cells and Conditioned Medium 6.5.5 Umbilical Cord Stem Cells 6.5.6 Epidermal/Epithelial Stem Cells 6.5.7 Bone Marrow-Derived Mesenchymal Stem Cells 6.6 Blood-Derived Factors for Corneal Regeneration: The Budding Potential 6.7 Discussion and Future Perspectives References 7 White Rot Exopolysaccharide: Avenues to Biomedical Applications 7.1 Introduction 7.2 Sources of Polysaccharides 7.2.1 Microbial Polysaccharides 7.2.2 Exopolysaccharides 7.3 Composition and Linkages 7.4 White Rot Fungi 7.4.1 Taxonomic Classification 7.4.2 General Characteristics of White Rot Fungi 7.5 Biomedical Applications 7.5.1 Immunomodulating and Antitumor Activity 7.5.2 Antimicrobial Activity 7.5.3 Antiinflammatory Activity 7.5.4 Antidiabetic Activity 7.5.5 Hepatoprotective Activity 7.5.6 Antioxidant Potential 7.5.7 Prebiotic Activity 7.5.8 Nutraceutical Potential and Functional Foods 7.5.8.1 Nutraceutical Versus Functional Foods and Pharmaceuticals 7.5.8.2 Potential of White Rot Polysaccharide as Nutraceuticals and Functional Food 7.6 Conclusion References Section II Health, Disease, and Management 8 Membrane Lipids From Cellular Barriers to Health and Homeostasis 8.1 Introduction 8.2 Phospholipids as a Backbone to Membrane Formation 8.3 Lipid Transbilayer Asymmetry 8.4 Aminophospholipids in Health and Diseases 8.5 Cardiolipins as Unique Lipids and Their Functions in Mitochondria 8.6 Phosphatidylinositol Phosphates (PIP) and Signalling Molecules 8.7 Lipid–Protein Interactions as Unique Fingerprints 8.8 Membrane Lipids Regulate Virus Entry and Replication 8.9 Lipid Therapy as a Natural Medicine 8.10 Conclusions Acknowledgements References 9 Childhood Cataract: A Clinico-Social Profile 9.1 Introduction 9.2 Classification of Childhood Cataracts 9.2.1 Age of Onset 9.2.1.1 Congenital Cataract 9.2.1.2 Developmental Cataract 9.2.2 Etiology 9.2.2.1 Genetic/Hereditary 9.2.2.2 Secondary 9.2.2.3 Traumatic Cataract 9.2.2.4 Intrauterine Infections 9.2.2.5 Iatrogenic 9.2.3 Morphology 9.3 Maternal Malnutrition and Intrauterine Infections 9.3.1 Maternal Malnutrition 9.3.2 Intrauterine Infections 9.4 Symptoms, Diagnosis, and Treatment 9.4.1 Symptoms and Diagnosis 9.4.2 Treatment for Childhood Cataract 9.5 Prevalence and Epidemiology of Childhood Cataract 9.6 Social Factors Affecting Health-Seeking Behaviour 9.7 Economic Burden of Childhood Bindness 9.8 Psychosocial Impact On Children and Family 9.9 Conclusion References 10 Evidence-Based Practice in Neurodegenerative Disorders: Approaches and Challenges 10.1 Introduction 10.2 Need for Evidence-Based Medicine in Neurodegenerative Disorders 10.3 Evidence-Oriented Approach in the Case of Neurodegenerative Diseases 10.3.1 Screening and Identification of the Problem 10.3.2 Accessing Sources of Information 10.3.3 Analyzing Information / Evaluation of Information 10.3.4 Information Implementation to the Patient 10.3.5 Efficacy Evaluation of This Application On a Patient 10.3.5.1 Research Outcome Utilization Or Response Scale 10.4 Difficulties and Challenges for Evidence-Based-Oriented Approach Against Neurodegenerative Diseases 10.4.1 Heterogeneity in Population 10.4.2 Lack of Etiological Studies 10.4.3 Insufficient Data 10.4.4 Publication Bias 10.4.5 Discordant Reviews 10.5 Concluding Remarks References 11 Pragmatic Utilization of Technology in Dentistry: Current Status and Future Perspectives 11.1 Introduction 11.2 Stem Cells 11.2.1 The Three Main Categories 11.2.1.1 Dental Pulp Stem Cells (DPSCs) 11.2.1.2 Stem Cells From Human Exfoliated Deciduous Teeth (SHED) 11.2.1.3 Periodontal Ligament Stem Cells (PDLSCs) 11.2.1.4 Stem Cells From Apical Papillae (SCAP) 11.2.1.5 Dental Follicle Precursor Cells (DFPCs) 11.2.2 Applications of Stem Cell Therapy in Dentistry 11.2.2.1 Regeneration of the Periodontal Ligament 11.2.2.2 Regeneration of the Dentin and Pulp 11.2.2.3 Regeneration of the Oromaxillofacial Structure Craniofacial Defects 11.2.2.4 Soft Tissue Reconstruction 11.2.2.5 Apexification and Apxogenesis 11.2.2.6 Tooth Regeneration 11.2.3 Future Perspectives 11.3 Gene Therapy 11.3.1 Gene Therapy Is a Two-Step Procedure 11.3.1.1 There Are Two Methods of Delivery of the Vector: In Vivo Or Ex Vivo 11.3.1.2 Vectors 11.3.2 Applications of Gene Therapy in Dentistry 11.3.2.1 Gene Therapy for Bone Repair 11.3.2.2 Gene Therapy for Salivary Glands 11.3.2.3 Gene Therapy for Cancer 11.3.2.4 Gene Therapy for Autoimmune Diseases 11.3.2.5 Gene Therapy for Pain Management 11.3.2.6 Gene Therapy for Orthodontic Tooth Movement 11.3.2.7 Gene Therapy for DNA Vaccinations 11.3.2.8 Gene Therapy for Growth of New Teeth 11.3.3 Challenges in Gene Therapy 11.4 Nanotechnology 11.4.1 Various Types of Nanostructures 11.4.2 Applications in Dentistry 11.4.2.1 Diagnosis 11.4.2.2 Preventive Dentistry 11.4.2.3 Restorative Dentistry 11.4.2.4 Prosthodontics 11.4.2.5 Endodontics 11.4.2.6 Orthodontics 11.4.2.7 Oral Surgery 11.4.2.8 Periodontics 11.4.2.9 Dental Nanorobots 11.4.3 Challenges Faced By Nanodentistry 11.5 Conclusion References 12 Stress Deregulates Memory Consolidation Through Epigentic Modifications 12.1 Introduction 12.2 Neurocircuitry of Memory Consolidation and Extinction 12.3 Memory Consolidation and Stress 12.4 Stress Effects On Extinction Learning 12.5 Epigenetics, Memory, and Stress 12.6 Conclusion References 13 The Management of Autism Spectrum Disorder: Challenges Ahead 13.1 Introduction 13.2 Management of Autism Spectrum Disorder 13.3 “Five-Fingers-Approach” for Management of ASD 13.3.1 Behavioral Therapy 13.3.2 Educational Therapy 13.3.3 Focused Interventions and Therapies 13.3.4 Complementary and Alternative Therapies 13.3.5 Pharmacotherapy 13.4 General Guidelines 13.5 Challenges Ahead References 14 Genetics of Left Ventricular Dysfunction in Coronary Artery Disease 14.1 Introduction 14.2 Inflammatory Pathways 14.2.1 Inflammation 14.2.2 The Role of Inflammation in Heart Failure 14.2.3 Inflammatory Cytokines and HF 14.2.4 Effect of Cytokines On LV Function 14.2.5 Effect of Cytokines On LV Remodelling 14.2.6 Association of Cytokine Gene Polymorphism With LVD 14.3 Sarcomeric Proteins 14.3.1 Sarcomeric Cytoskeletal Proteins 14.3.1.1 Titin 14.3.1.2 Myosin Binding Protein-C 14.3.2 Genetic Polymorphisms in Sarcomeric Genes and LVD 14.4 Signalling Pathway 14.4.1 Renin-Angiotensin-Aldosterone System 14.4.1.1 Components of RAAS 14.4.1.2 RAAS Gene Polymorphisms 14.4.1.3 ACE I/D Polymorphism and LV Remodeling After MI 14.4.1.4 ACE I/D Polymorphism and HF Severity and Progression 14.4.1.5 AT1 A1166C Gene Polymorphism 14.4.1.6 CYP11B2 T-344C Gene Polymorphisms 14.4.1.7 Genetic Polymorphisms in RAAS and LVD 14.4.2 .-Adrenergic Signalling Pathway 14.4.2.1 1-Adrenoceptor 14.4.2.2 2-Adrenoceptor 14.4.2.3 Adnergic Receptors and Congestive HF 14.4.2.4 1-Adrenoceptor Variants and LVD 14.4.3 JAK-STAT Signaling Pathway 14.4.3.1 STATs 14.4.3.2 STAT Signaling in Cardiovascular Diseases 14.5 Myocardial Remodeling 14.5.1 Matrixmetalloproteinases 14.5.1.1 Matrix MMPs and HF Process 14.5.1.2 MMP Gene Polymorphisms 14.5.1.3 Matrix Metalloproteinases-2 (MMP2) 14.5.1.4 Matrix Metalloproteinases-7 (MMP7) 14.5.1.5 Matrix Metalloproteinases-9 (MMP9) 14.6 Multigenetic and Multianalytical Approach in LVD Acknowledgements References 15 Genetics of Diabetic Nephropathy: A Review 15.1 Introduction 15.2 Epidemiology of Diabetic Nephropathy 15.3 Diagnosis of Diabetic Nephropathy 15.4 Classification of Diabetic Nephropathy 15.5 Pathophysiology of Diabetic Nephropathy 15.5.1 Metabolic Factors 15.5.2 Hemodynamic Factors 15.6 Genetics of Diabetic Nephropathy 15.6.1 Advanced Glycation End Products 15.6.2 Oxidative Stress 15.6.3 Hexosamine Pathway 15.6.4 Aldose Reductase (Polyol) Pathway 15.6.5 Renin Angiotensin System 15.6.6 Endothelin Pathway 15.7 Strategies to Identify Genes Associated With Diabetic Nephropathy 15.7.1 Linkage Analysis 15.7.2 Association Studies 15.7.2.1 Genome Wide Association Studies 15.7.2.2 Candidate Gene Studies 15.7.3 Next-Generation Sequencing 15.7.3.1 Exome Sequencing 15.7.3.2 RNA Sequencing 15.8 Differentially Expressed Genes in Diabetic Nephropathy 15.9 Genes Involved in Diabetic Nephropathy 15.9.1 ADIPOQ 15.9.2 TGF-1 15.9.3 TCF7L2 15.9.4 VEGFA 15.9.5 ELMO1 15.10 Epigenetics and DN 15.11 Concluding Remarks References 16 Human Y Chromosome: Genetic Markers, Implications, and Pathologies 16.1 Introduction 16.2 Evolution of Y Chromosome 16.3 Structure of Y Chromosome 16.4 Y Chromosome: Functions and Associated Pathologies 16.4.1 Testis Development and SRY Gene 16.4.2 Hostile to Turner Syndrome Impact 16.4.3 Oncogenic Effects of Y Chromosome 16.4.4 Other Pathological Conditions 16.5 Y-Chromosome Markers 16.5.1 Types of Y-Chromosome Markers 16.6 Y Chromosome as Population Marker 16.7 Y-Chromosome Haplogrouping 16.8 Conclusion References 17 Role of Repair Gene Polymorphism and Hypermethylation of GSTP Gene in the Risk of Prostate Cancer 17.1 Introduction 17.2 Historical Background 17.2.1 What Is a Prostate? 17.2.2 Benign Prostatic Hyperplasia 17.2.3 Tumor-Specific Antigens and Antibodies 17.2.3.1 Prostate-Specific Antigens 17.2.3.2 Tumor-Specific Antibodies 17.3 Epidemiology of Prostate Cancer 17.3.1 International Statistics 17.3.2 Asian Statistics 17.3.3 Indian Statistics 17.4 Risk Factors Involved in Prostate Cancer 17.4.1 Age and Ethnicity 17.4.2 Family History 17.4.3 Socio-Economic Conditions 17.4.4 Occupation 17.4.5 Physical Activity 17.4.6 Diet 17.4.7 Smoking 17.4.8 Vasectomy 17.4.9 Benign Prostatic Hyperplasia 17.4.10 Alcohol Consumption 17.5 Polymorphisms of DNA Repair Genes 17.5.1 Role of Xeroderma Pigmentosum Group D (XPD) Gene 17.5.2 Role of Xeroderma Pigmentosum Group C (XPC) Gene 17.6 Polymorphisms of Metabolic Genes 17.7 Methylation 17.7.1 Methylation in GSTP1 Gene 17.8 Conclusions References 18 Lymphatic Filariasis-Visceral Leishmaniasis Coinfection 18.1 Introduction 18.2 Clinical Manifestations 18.3 Lymphatic Filariasis and Visceral Leishmaniasis Coinfection in Rodents 18.4 Lymphatic Filariasis and Visceral Leishmaniasis Coinfection in Human 18.5 Immune Response Against Lymphatic Filariasis and Visceral Leishmaniasis 18.6 Immune Responses in Leishmania–Filaria Coinfection 18.7 Conclusion References 19 Metabolic Dysregulation, Oncogenes, and Tumor Suppressors: A Highly Orchestrated Performance to Induce Carcinogenesis Abbreviations 19.1 Introduction 19.2 Glucose Metabolism in Cancer Cells 19.3 Aerobic Glycolysis Pathway 19.4 Kreb’s Cycle 19.4 Role of Oncogenes and Tumor Suppressor Genes in Aerobic Glycolysis 19.4.1 Hypoxia Inducible Factor 19.4.2 Protein Kinase B 19.4.3 Tumor Protein P53 19.5 Pentose Phosphate Pathway 19.6 Role of Oncogenes and Tumor Suppressor Genes in Pentose Phosphate Pathway 19.6.1 Ras 19.6.2 Nuclear Factor Erythroid 2-Related Factor-2 19.6.3 Tumor Protein P53 References 20 Transthyretin Cardiac Amyloidosis: Recent Advances in Diagnosis and Treatment 20.1 Introduction 20.2 Molecular Mechanism Driving Transthyretin Amyloidogenesis 20.3 Diagnostic Approaches for Transthyretin Cardiac Amyloidosis 20.4 Therapeutic Strategies Undertaken for Transthyretin Cardiac Amyloidosis 20.5 Conclusion References 21 Pathophysiology of Diabetes-Induced Foot Ulcers and Therapy Options 21.1 Introduction 21.2 Classification of Diabetic Foot Ulcers 21.3 Microbial Loading in Diabetic Foot Ulcer 21.4 Pathophysiology of the Diabetic Foot Ulcer 21.4.1 Peripheral Neuropathy 21.4.1.1 Treatment of Peripheral Neuropathic Disease 21.5 Peripheral Arterial Disease 21.6 Role of Reactive Oxygen Species in Diabetic Foot Ulcer 21.6.1 Treatment of Reactive Oxygen Species 21.7 Charcot Foot Pathophysiology 21.7.1 The Microvascular Structure and Bone Turnover 21.7.2 Charcot Treatment 21.8 Role of Flavonoids in the Treatment of Diabetic Foot Ulcers 21.8.1 Catechin 21.8.2 Morin 21.8.3 Hesperidin (hesperetin-7-Rhamnoglucoside) 21.8.4 Genistein 21.8.5 Rutin: (3, 30, 40, 5, 7-Pentahydroxyflavone-3-Rhamnoglucoside) 21.8.6 Naringenin: (NA), (4', 5, 7-Trihydroxy Flavanones 7-Rhamnoglucoside) 21.8.7 Puerarin 21.8.8 Luteolin 21.8.9 Fisetin: (3, 39, 49, 7-Tetrahydroxyflavone) 21.8.10 Naringin: Naringin: (4', 5, 7-Trihydroxy Flavanones 7-Rhamno Glycoside) References 22 Current Challenges in Immunobiology of Autoimmunity and Cancer 22.1 Introduction 22.1.1 What Is Autoimmunity? 22.2 What Are Self-Antigens? 22.3 Some of the Proposed Ways in Which Self-Antigens Can Promote Autoimmunity 22.3.1 Alteration of Self-Antigens 22.3.2 Release of Sequestered Self-Antigens 22.3.3 Cross-Reaction With Foreign Antigens 22.4 Autoimmunity and Diseases 22.5 The Fight Between Self and Non-Self 22.6 Etiology of Autoimmune Diseases 22.6.1 Genetic Factors 22.6.2 Environmental Factors 22.6.3 Hormonal Factors 22.6.4 Co-Occurrence of Autoimmune Diseases 22.7 Selective Immunotherapies for Autoimmune Diseases (Mackay, 2001) 22.7.1 Monoclonal Antibodies Or Blocking Antagonists 22.7.2 CTLA-4 22.7.3 Regulatory Cytokines 22.7.4 Restoration of Tolerance 22.8 Cancer 22.9 Cancer Immunotherapy 22.10 Divisions of Cancer Immunotherapy 22.10.1 Checkpoint Inhibitors 22.10.1.1 Key Challenges 22.10.2 Cytokines 22.10.2.1 Key Challenges 22.10.3 Cell-Based Immunotherapy 22.10.3.1 Key Challenges 22.10.4 Cancer Vaccines 22.10.5 Immunoadjuvants 22.10.5.1 Key Challenges 22.11 Concluding Remarks Acknowledgments References 23 Human Papillomavirus (HPV): Molecular Epidemiology of Infection and Its Associated Diseases 23.1 Introduction 23.1.1 Historical Perspective and Evolution of Human Papillomaviruses 23.1.2 Global Occurrence and Epidemiology of Human Papillomaviruses 23.1.3 General Classification of HPV 23.2 Structural Features 23.3 Genome Organization 23.4 Pathophysiology: Mode of Infection and Transmission 23.4.1 Viral Entry Into the Host Cell 23.4.2 Viral Genome Replication 23.5 HPV Diseases and Their Association With Cancer 23.5.1 Diseases Associated With HPV 23.5.2 HPV Cancer 23.5.3 Modulatory Role of HPV Proteins On Oncoproteins and Tumor Suppressor Genes in Cancer Progression 23.6 Diagnosis of Human Papilloma Viral Infections 23.6.1 Presence of Warts in the Human Body Indicates HPV Infection 23.6.2 Clinical Laboratory Tests 23.6.3 Molecular Diagnosis 23.6.3.1 Nucleic Acid Hybridization Method 23.6.3.2 Signal Amplification Detection Method 23.6.3.3 DNA Amplification Method 23.7 HPV Vaccines 23.7.1 Bivalent Vaccine 23.7.2 Quadrivalent Vaccine 23.7.3 Nonavalent Vaccine 23.7.4 HPV Vaccine Dose Schedule 23.8 HPV MiRNAs 23.9 Conclusion Acknowledgments References 24 Challenges of Multidrug-Resistant Microbes On Public Health 24.1 Introduction 24.2 Common Antibiotics Used in Aquaculture 24.3 Mechanisms Involved in Multidrug Resistance of Bacteria 24.3.1 Enzyme Degradation 24.3.2 Mutation at Binding Site Or Target Protein 24.3.3 Downregulation of Outer Membrane 24.3.4 Horizontal Gene Transfer 24.3.5 Efflux Pumps 24.4 Antimicrobial Resistance in Aquaculture 23.5 Mitigation References 25 Role of Probiotics in the Prevention and Management of Obesity: What Have We Learned So Far? Abbreviations 25.1 Introduction 25.2 Environment and Obesity 25.3 Current Therapeutic Strategies for Treating Obesity and Their Limitations 25.4 Role of Gut Microbiota in the Human Body 25.5 Diet-Induced Alterations in Gut Microbiota and Their Relationship With Obesity 25.6 Emergence of Probiotics and Definitions 25.7 Probiotics as Medicines 25.8 Probiotics in the Management of Obesity: Lessons Learned From Animal Studies and Clinical Trials 25.9 Commercial Formulations of Probiotics 25.10 Summary and Conclusions Acknowledgments References Section III Therapeutics and Novel Approaches 26 Protease Inhibitors of Marine Origin: Promising Anticancer and HIV Therapies 26.1 Introduction 26.2 Role of Proteases in Cancer Progression 26.2.1 Matrix Metalloproteinases 26.2.2 Urokinase-Type Plasminogen Activator 26.2.3 Apoptosis and Caspases 26.2.4 Lysosomal Proteases 26.2.5 Serine Protease 26.3 Protease Inhibitors of Marine Origin With Potent Anticancer Properties 26.4 Recent Developments On HIV-PIs Towards Malignant Cancers 26.5 Different Pathways Targeted By HIV-PIs 26.5.1 AKT Pathways 26.5.2 ER Stress 26.5.3 Autophagy 26.5.4 Proteasome 26.6 HIV PIs With Potent Antitumor Activity 26.6.1 Nelfinavir 26.6.2 Lopinavir/Ritonavir 26.6.3 Saquinavir 26.6.4 Indinavir 26.7 Discussion and Future Directions 26.8 Conclusion Acknowledgements References 27 Skin Stem Cells: Therapeutic Potential in Vitiligo 27.1 Introduction 27.2 Stem Cell Niches in Skin 27.3 Stem Cells in Treatment of Vitiligo 27.3.1 Hair Follicle Melanocyte Stem Cells 27.3.2 Other Stem Cell Populations in Vitiligo 27.3.3 Surgical Methods Employing Stem Cell Populations 27.4 Conclusions References 28 Interplay of Cancer-Associated Fibroblasts (CAFs) and Tumor-Associated Macrophages (TAMs)... 28.1 Introduction 28.2 Cancer-Associated Fibroblasts 28.2.1 Different Origins of CAFs 28.2.1.1 Normal Fibroblasts 28.2.1.2 Epithelial Cells Through Epithelial-Mesenchymal Transition 28.2.1.3 Mesenchymal Cells 28.2.2 Role of CAF in Tumorigenesis And Metastasis 28.2.2.1 Support Primary Tumor Growth 28.2.2.2 Sustaining Invasion and Metastasis of Tumor Cells 28.2.2.3 Induce Inflammation in Cancer Regions 28.2.3 CAFs as Potential Targets of Anti-Cancer Therapy 28.3 Tumor-Associated Macrophages 28.4 Conclusions References 29 Lantibiotics: Strengthening Our Armor Against Antibiotic-Resistant Pathogens 29.1 Introduction 29.1.1 Antimicrobial Natural Products 29.1.2 Ribosomally Synthesized and Post-Translationally Modified Peptides 29.1.3 Lantibiotics 29.1.4 Gene Organization 29.2 Genome Mining Studies for Discovery of Novel Lantibiotics 29.2.1 Class I Lantibiotics 29.2.1.1 Mode of Action of Class I Lantibiotics 29.2.1.2 Heterologous Production of Class I Lantibiotics 29.2.2 Class II Lantibiotics 29.2.2.1 Mode of Action of Class II Lantibiotics 29.2.2.2 Heterologous Production of Class II Lantibiotic 29.2.3 Class III Lantibiotics 29.2.3.1 Heterologous Production of Class III Lanthipeptides 29.2.4 Class IV Lantibiotics 29.2.4.1 Heterologous Production of Class IV Lanthipeptides 29.2.5 Lanthidins, Class V Lanthipeptides 29.2.4.1 Heterologous Production of Class V Lanthipeptides 29.3 Structure-Activity Relationship Studies 29.3.1 Impact of Altering Bonds and Bridges 29.3.2 Substitution of Aromatic Amino Acid 29.3.3 Substitution of Charged Amino Acid 29.3.4 Other Sites 29.4 Conclusion and Future Prospects References 30 Traditional Medicines for the Control of Leishmaniasis: Experimental Studies 30.1 Introduction 30.1.1 Vaccines 30.1.2 Chemotherapy 30.1.3 Immunology 30.2 Traditional Medicines 30.2.1 In Vitro Antileishmanial Activity of Plant Extracts 30.2.2 In Vivo Antileishmanial Activity of Plant Extracts 30.3 Conclusion and Future Implications References 31 Metal-Embedded Complexes: Accelerated Antimicrobial Activity Against Microorganisms 31.1 Introduction 31.2 Overview of Microbes Present in Environment 31.2.1 Bacteria 31.2.2 Fungi 31.2.3 Virus 31.3 Role of Metals in Biomedical Chemistry 31.4 Antimicrobial Mechanism of Metal Complexes 31.5 Metal Complexes as Antimicrobial Agents 31.5.1 First Transition Series Metal Complexes 31.5.2 Second and Third Transition Series Metal Complexes 31.6 Metallosurfactant as Antimicrobial 31.6.1 Metallosurfactants With Metal Ions in Hydrophilic Head 31.6.2 Metallosurfactants With Metallic Counter Ion 31.7 Conclusion References Section IV Drugs and Delivery Systems 32 Stem Cells: Emerging Novel Approaches to Drug Research and Disease Therapeutics 32.1 Introduction 32.2 Classification of Stem Cells and Their Applications in Medicine 32.2.1 Classification of Stem Cells 32.2.1.1 Classification I 32.2.1.2 Classification II 32.2.1.3 Multipotent Stem Cell 32.2.1.4 Unipotent Stem Cell 32.2.2 Clinical Applications of Stem Cells 32.2.2.1 ESCs in Regenerative Medicine 32.2.2.2 TSPSCs in Regenerative Medicine 32.2.2.3 MSCs/Stromal Cells in Regenerative Medicine 32.2.2.4 UCSCs in Regenerative Medicine 32.2.2.5 BMSCs in Regenerative Medicine 32.2.3 Applications in Other Medical Disorders 32.2.3.1 In Neurodegeneration and Brain Or Spinal Cord Injury 32.2.3.2 In Frailty Syndrome 32.2.3.3 In Cardiovascular Disease 32.2.3.4 In Blood-Cell Formation 32.2.3.5 In Regrowing Teeth 32.2.3.6 In Cochlear Hair Cell Regrowth 32.2.3.7 In Disorders of Pancreatic Beta Cells 32.3 Challenges Facing Stem Cell Therapy 32.4 Conclusions References 33 Bioinformatics Review in MiRNA System Biology and Drug Discovery 33.1 Introduction 33.2 MiRNA 33.3 Target Prediction in MiRNAs 33.4 MiRNA Biogenesis and Function 33.5 Tools for MiRNA Biogenesis and Functional Analysis 33.6 System Biology 33.7 Tools Used for Network Analysis in System Biology 33.8 Pathway and Network Analysis 33.9 Drug Design 33.10 Structure-Based Drug Design 33.11 Target Identification 33.12 Binding Site Prediction 33.13 Molecular Docking 33.14 A Case Study: Computational Repositioning of Ethno Medicine-Elucidated Anti-Harper Drug Target E6 33.15 Conclusion Acknowledgments References 34 Biomaterial-Based Nanofibers for Drug Delivery Applications 34.1 Nanofibers 34.1.1 History of Nanofibers 34.1.2 Characteristics of Nanofibers 34.2 Types of Methods for Producing Nanofibers 34.2.1 Self-Assembly Method 34.2.2 Centrifugal Spinning Method 34.2.3 Freeze-Drying Method 34.2.4 Electrospinning Method 34.2.4.1 Types of Electrospinning 34.2.4.2 Recent Advances in Electrospinning 34.3 Biomaterials for Nanofibers 34.3.1 Alginate 34.3.2 Chitosan 34.3.3 Collagen 34.3.4 Gelatin 34.3.5 Albumin 34.3.6 Silk Proteins 34.3.6.1 Silk Sericin 34.3.6.2 Silk Fibroin 34.3.7 Silk Fibroin Nanofibers 34.4 Applications in Drug Delivery 34.4.1 Wound Healing 34.4.2 Diabetic Wound Healing 34.5 Conclusions References 35 Therapeutic Translational Potential of Surface-Decorated Nanoparticles 35.1 Introduction 35.2 Surface-Decorated Nanoparticles in Diagnosis of Diseases Via Imaging 35.2.1 MRI 35.2.2 CT 35.2.3 PET 35.2.4 Fluorescence Imaging 35.2.4.1 QDs 35.2.4.2 Silica NPs 35.3 Surface-Decorated Nanoparticles in Treatment of Diseases Via Receptor Targeting 35.3.1 CD44 Targeting 35.3.2 Folate Receptor 35.3.3 Asialoglycoprotein Receptor (ASGPR) 35.3.4 Epidermal Growth Factor Receptor (EGFR) 35.3.5 Tumour-Associated Glycoprotein 72 (TAG 72) Receptor 35.3.6 TransferrinReceptors (TFRs) 35.3.7 Tyrosine Kinase Receptors 35.3.8 Vascular Endothelial Growth Factor Receptors (VEGFRs) 35.3.9 Integrin Receptors 35.3.10 Death Receptors 35.3.11 Mannose Receptor 35.4 Patented Surface-Decorated NPs for Theranostics 35.5 Limitations and Perspectives 35.6 Conclusion References Section V Nutra-Chemistry 36 Towards Developing Biofortified Food Crops for Enhancing Nutritional Aspects and Human Health 36.1 Importance of Biofortification in Combating Micronutrient Deficiencies 36.2 Various Modes/Techniques of Biofortification 36.2.1 Biofortification Through Fertilizer Application 36.2.2 Biofortification Through Traditional Plant Breeding 36.2.3 Biofortification Through Transgenic Techniques 36.3 Agronomic Approaches for Biofortification 36.4 Some Biofortified Crops 36.4.1 Legumes and Pulses 36.4.2 Chickpea 36.4.3 Lentil 36.4.4 Beans 36.4.5 Cowpea 36.5 Cereals 36.5.1 Pearl Millet 36.5.2 Maize 36.5.3 Rice 36.6 Vegetables 36.6.1 Potato 36.6.2 Sweet Potato 36.6.3 Cassava 36.6.4 Lettuce 36.6.5 Carrot 36.6.6 Cauliflower 36.7 FRUITS 36.7.1 Tomato 36.7.2 Banana 36.7.3 Grapes 36.7.4 Mango 36.8 Oilseeds 36.8.1 Mustard 36.8.2 Canola 36.9 Conclusions References 37 Production of Sesquiterpene Lactones in Family Asteraceae: Structure, Biosynthesis, and Applications 37.1 Introduction 37.2 Structure of Sesquiterpene Lactones 37.2.1 Germacranolides 37.2.2 Eudesmanolides 37.2.3 Guaianolides 37.2.4 Pseudoguaianolides 37.3 Biosynthesis of STLs 37.3.1 Biosynthesis of Germacranolides 37.3.2 Biosynthesis of Guaianolides, Pseudoguaianolides, and Eudesmanolides 37.4 Medicinal Properties of Various STLs 37.4.1 Anticancer and Cytotoxic Activity 37.4.2 Anti-Inflammatory Activity 37.4.3 Antimicrobial and Antibacterial Activity 37.4.4 Antimalarial Activity 37.4.5 Antiulcer Activity 37.4.6 Antifungal Activity 37.5 Concluding Remarks References 38 Multiple Therapeutic Applications of Pomegranate Fruit and Its Bioactive Phytochemicals in Health and Disease 38.1 Introduction 38.2 History of Pomegranate 38.3 Phytochemicals Present in Different Pomegranate Parts 38.4 Cardioprotective and Antiosteoarthritis Effects of Pomegranate 38.5 Neuroprotective Effects of Pomegranate 38.6 Pomegranate Bioactive Constituents Target Multiple Oncogenic Signaling and Molecular Mechanisms for the Prevention and Management of Cancer 38.7 Antibacterial and Antiviral Activities of Pomegranate Fruit and Juice 38.8 The Prebiotic Properties of Edible and Non-Edible Parts of Pomegranate 38.9 Future Opportunities, Challenges, and Conclusion Acknowledgments References Index