Banca de DEFESA: JOHNNY CARVALHO DA SILVA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : JOHNNY CARVALHO DA SILVA
DATE: 24/02/2025
TIME: 14:00
LOCAL: Plataforma Teams
TITLE:

EVALUATION OF THE IMMUNE RESPONSE IN SENESCENT AND NON-SENESCENT PULP CELLS AND THE SEARCH FOR SENOTHERAPEUTIC PEPTIDES

KEY WORDS:

“Senescence; Aging; Dental Pulp; Peptides."

PAGES: 100
BIG AREA: Ciências da Saúde
AREA: Odontologia
SUMMARY:

“Cellular senescence is characterized by the irreversible arrest of the cell cycle, accompanied by morphological, metabolic, lysosomal, and secretory factor alterations. Although it initially evolved as a mechanism to limit the proliferation of aged or damaged cells, senescence contributes to aging, resulting in age-related diseases and the decline of cellular functions. These changes also affect dental pulp cells, impairing their defensive and sensory functions and potentially compromising the success of conservative endodontic treatments. This study was divided into three chapters. Chapter 1 aims to explore senescence in dentistry, focusing on the dentin-pulp complex through a literature review with bibliometric analysis. The research also investigates the scientific literature to identify dental products that induce cellular senescence. Furthermore, the study discusses potential strategies to mitigate the effects of senescence. Our study concludes that, despite increasing research on senescence in the dentin-pulp complex, the topic requires further exploration. Accelerating and deepening studies to identify products that induce or mitigate senescence and translating this knowledge into effective clinical solutions is crucial. Chapter 2 aimed to evaluate the morphology, migration, proliferation, viability, and immune response of human dental pulp cells in senescence and under inflammatory stimulation. Initially, senescence was induced using doxorubicin and confirmed by β-galactosidase staining. To simulate an in vitro inflammatory response, lipopolysaccharide (LPS) and interferongamma (IFN-γ) were used. Morphological changes were analyzed by scanning electron microscopy. Cell proliferation and viability were assessed by trypan blue exclusion, while migration capacity was determined using the scratch assay. The immune response was investigated by assessing the expression of pro-inflammatory cytokine genes, such as indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), and anti-inflammatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor beta 1 (TGF-β1), using qPCR. The results demonstrated that senescent cells showed increased size, fewer extensions, reduced migration, proliferation, and viability, along with increased expression of IDO, TNF-α, and IL-6. TGF-β1 expression was reduced in the LPS-treated group, while IL-10 expression increased without statistical significance. Chapter 3 evaluated the senotherapeutic potential of a library of 15 peptides designed using artificial intelligence. This peptide library, synthesized after in silico design, was tested before and after senescence induction with doxorubicin. The screening of peptides was performed using βgalactosidase staining, while cell viability was assessed using the MTT assay, and nitric oxide (NO) production was measured using the Griess method. Among the peptides tested, two peptides, C2 and C3, showed good potential, as they maintained high cell viability even at high concentrations, reduced β-galactosidase staining, and decreased nitrite production at low concentrations. Overall, the results of our study indicate the presence of exacerbated inflammation associated with immunosuppression, compromising the reparative potential of senescent dental pulp cells, along with reduced migration and proliferation. In this context, cellular senescence may negatively influence the prognosis of conservative endodontic treatments by impairing essential cellular functions. Additionally, several products used in the context of the dentin-pulp complex were observed to have the potential to induce pulp senescence. Thus, the search for new drugs with senotherapeutic potential emerges as a promising alternative to mitigate the effects of senescence in the dental pulp. In this regard, the most promising peptides from this initial analysis will be evaluated in future tests.”

COMMITTEE MEMBERS:
Externo à Instituição - WARLEY LUCIANO FONSECA TAVARES - UFMG
Externa à Instituição - ANA PAULA DIAS RIBEIRO - UFL
Interna - 1278451 - ELIETE NEVES DA SILVA GUERRA
Presidente - 3342495 - TAIA MARIA BERTO REZENDE