Advances in Molecular Pathology

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