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Vibrational nanospectroscopy applied to the study and characterization of extracellular vesicles in the uremic context

Grant number: 23/06583-0
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): January 01, 2024
Effective date (End): November 30, 2027
Field of knowledge:Biological Sciences - Biophysics - Radiology and Photobiology
Principal Investigator:Marcela Sorelli Carneiro Ramos
Grantee:Jéssica Verônica da Silva
Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

In the current stage of medicine, the clinical diagnosis of a patient is obtained through the analysis of clinical exams, comparison with standard values of physiological and genetic parameters, high precision medical images and detection of metabolites in biofluids such as blood or urine. However, even having a wide arsenal available for characterizing and measuring homeostasis, numerous cases of patients with similar symptoms and parameters, but affected by different diseases, are reported. Moreover, the response of different individuals to the same treatment can be quite different. The establishment of a precise and personalized medical diagnosis and therapy (theranostic) considering the needs and response potential of each individual is one of the great challenges of modern medicine, also called precision medicine by some. Obtaining new biomarkers, characterizing their dynamic molecular response and developing new therapeutic strategies, bearing in mind personalized molecular and genetic aspects are possible strategies for overcoming this challenge. In this project, inflammatory processes of systemic origin such as, for example, alterations in the phenotype of cells, the increase in the generation of reactive oxygen species (ROS), the expression of inflammatory cytokines, with rapid degeneration of the cardiovascular system and the increase in the number of circulating extracellular vesicles (EVs) derived from the accumulation of uremic toxins such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS) in the bloodstream, will be characterized by vibrational nanospectroscopy ("Surface Enhancement Raman Spectroscopy", SARS and "Photo-Induced Force Microscopy", PiFM) as well as conventional techniques of molecular and cellular biology of the systems involved. Finally, we believe that the obtained results will help in the understanding of new mechanisms involved in the cardiac and renal alterations induced by the uremic compounds PCS and IS, mediated by EVs.

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