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.
Author(s): Felipe Simon, Carmelo Bernabeu
Series: Advances in Experimental Medicine and Biology, 1408
Publisher: Springer
Year: 2023
Language: English
Pages: 335
City: Cham
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
