Advances in Molecular Pathology

Description

The present work corresponds to a compilation of independent contributions in the fields of endocrinology, immunity, cancer, neurobiology, and myology. Revision of current advances as well as novel findings in the form of original articles are presented in a balanced fashion. The book has been divided into three sections in line with the main subject: Molecular pathology of immune, inflammatory, and hemostatic disorders; Molecular pathology of endocrine and muscular disorders; and Molecular pathology of cancer: determinants and potential therapies. In the first section, contributing authors take the reader through the molecular pathology of immune responses, inflammation, and hemostasis, by collating an update on systemic autoimmune diseases, the therapeutic potential of statins in hemostasis, the effects of adrenergic stimulation on coagulation, the emerging field of physical burnout due to the mobility restrictions in response to the 2020 SARS-CoV-2 pandemic imposed worldwide, and the success of community-oriented muscular kinesic rehabilitation. The second section presents engaging results from a survey of iodine intake through the diet of pregnant females, an appraisal of the neuroprotective effect of dexmedetomidine, novel evidence on muscle physiopathology, describing the upregulation of CCL5/RANTES during cholestatic liver disease, the fibrotic response emerging in response to cholic and deoxycholic acids, and the altering effects of bile acids in autophagy and mitogenesis. In the third section, a comprehensive revision of cancer literature is offered with an emphasis on melanoma, myeloid-derived suppressor cells, microRNA-based diagnostic approaches, and new avenues for cancer immunotherapy. Altogether, these individual contributions offer a comprehensive and up-to-date outlook of the current state in the field of molecular pathology. Chapter 14 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com. Preface Contents Editors and Contributors Molecular Pathology of Immune, Inflammatory, and Hemostatic Disorders 1 Immune Responses at Host Barriers and Their Importance in Systemic Autoimmune Diseases Abstract 1.1 Introduction 1.2 Food Allergy 1.2.1 Initiation of Food Allergy at the Intestinal Mucosa 1.2.2 Initiation of Food Allergy at the Skin Barrier 1.2.3 Mechanisms of Oral Tolerance in Food Allergy 1.3 Systemic Lupus Erythematosus and Its Association with Mucosal Barriers 1.3.1 Dysbiosis of Intestinal Microbiota and “Leaky Gut” as Triggers of Inflammation in SLE 1.3.2 Initiation of SLE at the Skin Barrier 1.4 Rheumatoid Arthritis and Its Origin at Mucosal Barriers 1.4.1 Initiation of Rheumatoid Arthritis by Inflammation and Antigen Citrullination in the Oral Cavity 1.4.2 Initiation of Rheumatoid Arthritis by Antigen Citrullination at the Lung Mucosa 1.4.3 Dysbiosis of Intestinal Microbiota and “Leaky Gut” as Triggers of Inflammation in Rheumatoid Arthritis 1.5 Conclusions Statements and Declarations References 2 Statins and Hemostasis: Therapeutic Potential Based on Clinical Evidence Abstract 2.1 Introduction 2.2 Statins in Thrombotic Events 2.3 Statins in Vascular and Cardiovascular-Related Diseases 2.4 Metabolic Diseases and Related Risk Factors 2.5 Other Chronic Diseases 2.6 Molecular Mechanisms in Statins Improved Coagulation 2.7 Concluding Remarks Statements and Declarations References 3 Effects of Adrenergic Receptor Stimulation on Human Hemostasis: A Systematic Review Abstract 3.1 Introduction 3.1.1 Classification of Adrenergic Receptors 3.1.2 Characteristics of Adrenergic Receptors 3.1.3 Tissue Distribution of Adrenergic Receptors 3.1.4 Physiological Activity of Adrenergic Receptors 3.1.5 Therapeutic Modulation of Adrenergic Receptor-Signaling 3.1.6 Chronic Stimulation of Adrenergic Receptors 3.2 Methods 3.3 Results 3.3.1 Study Characteristics 3.3.2 Risk of Bias 3.3.3 Results of Individual Studies and Synthesis 3.3.4 Assessments of Certainty 3.4 Discussion 3.5 Strengths and Limitations 3.6 Conclusions Statements and Declarations References 4 α1-Adrenergic Stimulation Increases Platelet Adhesion to Endothelial Cells Mediated by TRPC6 Abstract 4.1 Introduction 4.2 Methods 4.3 Results 4.3.1 Platelet Adhesion Is Mediated by the α-1 Adrenergic Receptor 4.3.2 TRPC6 Activity Mediates Phenylephrine-Induced Platelet Adhesion to ECs 4.3.3 Phenylephrine, Terazosin and BI-749327 Do Not Show Cytotoxicity in ECs 4.3.4 TRPC6 Expression Mediates Phenylephrine-Induced Platelet Adhesion to ECs 4.3.5 TRPC6 Is Required for Endothelial Integrin αvβ3 Expression Induced by Phenylephrine, but not for P-Selectin and vWF 4.4 Discussion Statements and Declarations References 5 Physical Activity, Burnout, and Engagement in Latin American Students of Higher Education During the COVID-19 Pandemic Abstract 5.1 Introduction 5.2 Methods 5.3 Results 5.4 Discussion 5.5 Research Limitations Author Contributions Ethical Approval References 6 Small Plastics, Big Inflammatory Problems Abstract 6.1 Introduction 6.2 Immune System 6.3 Nervous System 6.4 Respiratory System 6.5 Circulatory System 6.6 Digestive System 6.6.1 Gut 6.6.2 Liver 6.6.3 Excretion 6.7 Reproductive System 6.8 Predisposition to Diseases Ethical Approval References 7 Impact of a Community-Based Pelvic Floor Kinesic Rehabilitation Program on the Quality of Life of Chilean Adult Women with Urinary Incontinence Abstract 7.1 Introduction 7.2 Methods 7.3 Ethical Aspects: 7.4 Results 7.5 Discussion 7.6 Conclusions Acknowledgements References Molecular Pathology of Endocrine and Muscular Disorders 8 Iodine Intake Based on a Survey from a Cohort of Women at Their Third Trimester of Pregnancy from the Bosque County Chile Abstract 8.1 Introduction 8.2 Methods 8.3 Results 8.3.1 Characteristic of Pregnant Women that Participated in the Study 8.3.2 Thyroid Physiological Parameters 8.3.3 Food Iodine Content and Estimated Iodine Consumption 8.3.4 Theorical Estimated Iodine Consumption (tEIC) and Calculated Iodine Consumption (cIC) 8.3.5 Matrix Correlation Analysis 8.4 Discussion 8.5 Conclusion Statements and Declarations References 9 Appraisal of the Neuroprotective Effect of Dexmedetomidine: A Meta-Analysis Abstract 9.1 Introduction 9.2 Methods 9.2.1 Eligibility Criteria 9.2.2 Information Sources and Search Strategy 9.2.3 Selection and Data Collection Processes 9.2.4 Data and Synthesis 9.2.5 Risk of Bias and Certainty Assessment 9.3 Results 9.3.1 Study Characteristics 9.3.2 Results of Syntheses 9.3.3 Risk of Bias and Certainty of Evidence 9.4 Discussion 9.5 Strenghts and Limitations 9.6 Conclusions Statements and Declarations References 10 Bile Acids Alter the Autophagy and Mitogenesis in Skeletal Muscle Cells Abstract 10.1 Introduction 10.2 Methods 10.2.1 Cell Culture 10.2.2 Treatments of C2C12 Myotubes 10.2.3 Protein Extraction 10.2.4 Western Blot 10.2.5 Plasmids 10.2.6 Amplification and Transfection of Plasmids 10.2.7 Luciferase Activity 10.2.8 Statistical Analysis 10.3 Results 10.3.1 Cholic and Deoxycholic Acids Impair Autophagy in C2C12 Myotubes 10.3.2 Cholic and Deoxycholic Acids Decrease PGC-1α Transcriptional Activity Without Altering TFAM Protein Levels in C2C12 Myotubes 10.4 Discussion 10.5 Conclusions Statements and Declarations References 11 Upregulation of CCL5/RANTES Gene Expression in the Diaphragm of Mice with Cholestatic Liver Disease Abstract 11.1 Introduction 11.2 Methods 11.2.1 Animals 11.2.2 Plasma Bile Acids Levels 11.2.3 Parameters of Liver Injury 11.2.4 Hepatomegaly 11.2.5 Measurement of Muscle Mass 11.2.6 Maximal Incremental Exercise Test 11.2.7 Grip Strength Test 11.2.8 RT-qPCR 11.2.9 Statistical Analysis 11.3 Results 11.4 Discussion 11.5 Conclusion Statements and Declarations References 12 Differential Fibrotic Response of Muscle Fibroblasts, Myoblasts, and Myotubes to Cholic and Deoxycholic Acids Abstract 12.1 Introduction 12.2 Methods 12.3 Results 12.4 Discussion 12.5 Conclusion Statements and Declarations References 13 BMAL1 Regulates Glucokinase Expression Through E-Box Elements In Vitro Abstract 13.1 Introduction 13.2 Methods 13.3 Results 13.4 Discussion Statements and Declarations References Molecular Pathology of Cancer: Determinants and Potential Therapies 14 Correlation Between Endoglin and Malignant Phenotype in Human Melanoma Cells: Analysis of hsa-mir-214 and hsa-mir-370 in Cells and Their Extracellular Vesicles Abstract 14.1 Introduction 14.2 Methods 14.3 Results 14.4 Discussion Statements and Declarations References 15 Increase in Frequency of Myeloid-Derived Suppressor Cells in the Bone Marrow of Myeloproliferative Neoplasm: Potential Implications in Myelofibrosis Abstract 15.1 Introduction 15.2 Methods 15.3 Results 15.3.1 Myeloproliferative Neoplasm Patients’ Clinical Data 15.3.2 The Frequency of T-MDSCs and PMN-MDSCs is Elevated in the Bone Marrow of MPNs Patients 15.3.3 The Frequency of T-MDSCs and PMN-MDSCs is Increased in the Peripheral Blood of MPNs Patients 15.3.4 MPNs-Related MDSCs Exhibited Immunosuppressive Capabilities 15.3.5 Fibrosis in the Bone Marrow of MPNs Patients 15.3.6 TGF-β1 Induces MDSC from Bone Marrow Mononuclear Cells 15.4 Discussion Statements and Declarations References 16 The “Ins and Outs” of Prostate Specific Membrane Antigen (PSMA) as Specific Target in Prostate Cancer Therapy Abstract 16.1 Introduction 16.2 Methods 16.3 Results 16.3.1 PSMA Localization is Restricted to Secretory Poles of Specific Epithelial Cells 16.3.2 Small Molecule PSMA-617 is not Selective for Prostate PSMA and Can Recognize Salivary and Kidney PSMA 16.3.3 J591-Based Minibody Binds a Portion of the Extracellular Domain of PSMA by the Region of Binding of PSMA-617 16.3.4 J591-Based Minibody is not Specific for Prostatic PSMA and Can React with PSMA of Other Tissues 16.3.5 PSMA KO Model Confirms J591-Based Minibody Specificity 16.4 Discussion Statements and Declarations References 17 Transforming Growth Factor-β1 in Cancer Immunology: Opportunities for Immunotherapy Abstract 17.1 Introduction 17.2 Transforming Growth Factor-β1 Signaling 17.3 Transforming Growth Factor-β Role in Cancer 17.4 Transforming Growth Factor-β and Cellular Immune System Interactions 17.4.1 TGF-β Regulates T-cell Activities and Function 17.4.2 TGF-β Promotes the Generation of CD4+ Regulatory T-cells 17.4.3 TGF-β Regulates Natural Killer Cell Function and Activity 17.4.4 TGF-β Represses Dendritic Cells Functionality 17.4.5 TGF-β1 Increases the Expansion and Function of Myeloid-Derived Suppressor Cells 17.4.6 TGF-β Regulates Tumor-Associated Macrophages Polarization and Function 17.4.7 Tumor-Associated Neutrophils and TGF-β 17.5 Perspectives for Targeting TGF-β1 in Cancer Immunotherapies 17.5.1 Immune Checkpoint Immunotherapy and TGF-β 17.5.2 Adoptive Cell Therapy/Chimeric Antigen Receptor (CAR) T-Cell Therapy and TGF-β 17.6 Concluding Remarks Statements and Declarations References Index