Ateneo - UPO

Deepen the understanding of metabolic, protein, and genetic biomarkers in diagnostics, risk prediction, and personalized therapies. Comprehend the application of biochemical and molecular biology techniques in diagnostics, assessing how methodological choices and analytical conditions influence result quality and its informational value in clinical practice. Understand the role and application of enzymatic and metabolic biomarkers in organ function assessment and the diagnosis of metabolic disorders. Develop an integrated perspective on the regulation of metabolic processes across different organs and tissues, analyzing how alterations in intracellular signaling pathways can disrupt cellular and systemic homeostasis.

1) Tietz Textbook of Laboratory Medicine 7th Edition - February 3, 2022 Author: Nader Rifai Language: English Hardback ISBN: 9780323775724 2) Trattato di Biochimica Clinica e Medicina di Laboratorio M. Ciaccio EdizioneI/2021 ISBN9788836230440 3) BIOCHIMICA CLINICA E MEDICINA DI LABORATORIO Casa Editrice:EDISES Autori :Ciaccio-Lippi Volume:UNICO Anno Edizione:2020 Numero Edizione:III ISBN:9788836230228 4) Medical Biochemistry, 6th Edition Authors : John W Baynes & Marek H. Dominiczak ISBN Number 9780323834506 Med, FRCPath Publication Date 18-08-2022 5) Medical Biochemistry Authors: Antonio Blanco and Gustavo Blanco Second Edition • 2022 ISBN 978-0-323-91599-1 6) Antonozzi-Gulletta Medicina di Laboratorio Logica e Patologia Clinica, III Edizione, Piccin

Understand how metabolic, protein, and genetic markers can be applied in diagnostic, predictive, and therapeutic contexts. Learn how biochemical and molecular biology techniques are used in diagnostics and evaluate how the choice of an analytical method and its application impact the quality of results and their clinical relevance. Gain knowledge on the diagnostic applications of enzymatic biomarkers and metabolic markers in assessing organ function and diagnosing metabolic disorders. Develop a comprehensive understanding of metabolic process regulation across different organs and tissues, and analyze how alterations in intracellular signaling pathways can disrupt homeostasis at both cellular and systemic levels.

Familiarity with key metabolic pathways and their regulatory mechanisms. Understanding of signal transduction processes and gene expression regulation. Strong knowledge of cell biology, with a focus on organelle interactions, cellular metabolism, and responses to environmental stimuli

Lectures will be delivered through slide presentations. In-class activities will include problem-solving exercises, quizzes, and case studies to illustrate specific issues in molecular diagnostics and guide students in their resolution. Students will also have the opportunity to complete exercises, quizzes, and case studies at home via the Moodle platform. For exam preparation, they can use the materials provided by the instructor, including: PDFs, slides, Handouts specifically prepared for the course, Selected scientific articles that provide deeper insights into the topics covered.

The PDF copies of the projected slides, the supplementary material, and all information regarding the course and exam procedures will be made available on the Moodle DIR platform (https://www.dir.uniupo.it/).

The objective of the exam is to assess the level of knowledge and depth of the course topics, as well as the reasoning abilities developed by the student. The exam consists of a written test with 40 questions covering all the topics discussed in the course, divided into: i) multiple-choice or true/false questions, and ii) open-ended questions requiring the resolution of problems related to the evaluation of laboratory test properties (sensitivity, specificity, predictive value) or a brief discussion of topics covered during the course. The exam will evaluate theoretical knowledge, critical thinking, reading comprehension (including exercises that require selecting the correct answer from several alternatives), and the ability to apply acquired knowledge to practical situations. The final grade will be expressed in thirtieths (minimum passing grade: 18). During the written test, no materials are allowed, but the use of a calculator is permitted. The program and exam details will be available on the Moodle DIR platform.

Biomarkers Purpose and significance of biomarkers Biological and diagnostic significance of protein, metabolic, and genetic biomarkers. Diagnostic, predictive, prognostic, efficacy, and evolution purposes of biomarkers. Protein and enzymatic biomarkers Protein biomarkers Major plasma proteins Inflammatory markers Tumor markers Proteomics in diagnostic settings Enzymatic biomarkers Criteria for choosing enzymatic biomarkers in clinical laboratories. Methods for determining enzymatic activity. General factors affecting enzyme levels in blood under healthy and diseased conditions. Factors influencing the diagnostic utility of an enzyme. Major enzymes used in clinical laboratories: biochemical basis of their function under normal conditions and biological rationale for their use as disease markers. Definition and diagnostic value of isoenzymes. Organ-specific enzyme patterns and disease conditions associated with increased or decreased transaminases, creatine kinase, lactate dehydrogenase, alkaline phosphatase, gamma-glutamyl transferase, amylase, lipase, trypsin, and cholinesterase. Biochemical and functional characteristics of markers for myocardial pathology: myoglobin and troponins. Metabolic biomarkers: clinical applications of metabolomics Overview of metabolomic analysis Congenital metabolic disorders "Biochemical" classification of laboratory markers used in diagnosing congenital metabolic disorders Metabolome investigations: diagnostic significance of free fatty acids, organic acids, and amino acids profiles. Proteome investigations and enzymatic assays: areas of application and limitations. Definition of diagnostic screening and its applications. Examples of congenital metabolic disorders investigated or potentially detectable by neonatal screening: phenylketonuria, tyrosinemia, cystinuria, congenital hypothyroidism, biotinidase deficiency, adrenogenital syndrome, galactosemia, organic acidemias (Maple Syrup Urine Disease/MSUD), isovaleric aciduria, propionic aciduria, methylmalonic aciduria. Urea cycle disorders, Medium-Chain Acyl-CoA dehydrogenase (MCAD) deficiency, congenital adrenal hyperplasia. Overview of metabolomic analysis in aging studies. Genomic biomarkers: clinical applications of molecular biology Introduction Classification and functional consequences of genetic alterations investigated in molecular diagnostics. Potentials and limitations of molecular tests. The choice of biological material for the investigation depending on the type of test and its purpose. Sensitivity and specificity of molecular tests. Main techniques used in molecular diagnostics. Molecular biomarkers in oncology Colon cancer biomarkers Breast cancer biomarkers Cell signaling in health and disease Calcium signaling Organ Biochemistry Biochemistry of skeletal muscle, smooth muscle, and cardiac muscle. Biochemistry of blood vessels. Endocrine regulation biochemistry Posterior pituitary hormones Vasopressin and oxytocin: structure, mechanism of action, and peripheral metabolic effects. Control of water-salt and blood pressure balance: Renin-angiotensin-aldosterone system. Anterior pituitary hormones, hypothalamic-pituitary axes, and their peripheral targets CRH/ACTH/cortical adrenal hormones, glucocorticoids, and mineralocorticoids: synthesis, structure, mechanism of action, and metabolic effects. Pathological alterations. GnRH/LH-FSH/sexual hormones: General overview of gonadotropins. Regulation, structure, receptors, and function. Sex hormones: progesterone, estrogens, androgens (biosynthesis from cholesterol and regulation by pituitary hormones, structure, and function). TRH/TSH/Thyroid hormones axis: regulation, synthesis, structure, mechanism of action, and metabolic effects. Hypothyroidism and hyperthyroidism: metabolic consequences. GHRH/GH/IGF1 axis: mechanism of action and metabolic effects. Pathological alterations. Intermediate pituitary hormones Pro-opiomelanocortin derivatives: melanocortins, endorphins, lipotropins. Structure, mechanism of action, and metabolic effects. Hormones regulating calcium and phosphate metabolism Parathyroid hormone and calcitriol (structure, biosynthesis, receptor/transduction, and function in regulating blood calcium). Vitamin D. Neuroendocrine regulation: neuromodulatory and hormonal molecules SNS and PNS signaling mechanisms. Catecholamines and stress response: structure, mechanism of action, and peripheral metabolic effects. Biogenic amines (dopamine and serotonin): structure, mechanism of action, and peripheral metabolic effects. Gastrointestinal hormones. Overview of the main hormones in this family. Regulation of energy metabolism and dysfunctions in metabolic syndrome Regulation of catabolic and anabolic processes PI3K/AKT/mTOR signaling pathway AMPK signaling pathway Sirtuins Insulin signaling pathway and systemic metabolic effects. Transcriptional control of energy metabolism. Molecular basis of metabolic syndrome Alterations in insulin signaling pathways and the homeostasis of glucose and lipid metabolism. Overview of caloric restriction, energy metabolism, and aging.

Be able to independently assess how pre-analytical and analytical conditions contribute to determining the quality and informational value of a laboratory result, and choose the most appropriate molecular test based on the chemical-physical principles underlying the test and the characteristics of the genetic marker being investigated. Know the main biochemical markers (protein and metabolic) used in laboratory diagnostics to assess organ function (mainly kidney and liver) and for the diagnosis of congenital metabolic diseases. Understand the key signaling pathways involved in the hormonal regulation of energy metabolism and how various pathological conditions can be characterized by alterations in energy metabolism, and how this knowledge can be used to identify new therapeutic targets. Have a solid understanding of the biochemistry of endocrine signaling, including the molecular mechanisms underlying hormonal regulation, the interaction between hormones and receptors, and the resulting cellular responses, in order to interpret the physiological and pathological implications of these processes.