https://repositorio.ufu.br/handle/123456789/5495 2026-10-08T18:31:18Z https://repositorio.ufu.br/handle/123456789/50436 Title: Avaliação de efeitos citotóxicos de um novo complexo de rutênio “Ru-Naftil” em modelo celular de câncer de próstata metastático Abstract: Prostate cancer remains one of the leading causes of cancer-related mortality among men worldwide, particularly in advanced stages such as metastatic castration-resistant prostate cancer, where resistance to hormonal therapy and limited chemotherapy efficacy compromise clinical outcomes. Ruthenium-based compounds have emerged as promising alternatives to conventional chemotherapy because of their distinct mechanisms of action and improved tumor selectivity. In this study, a novel ruthenium(II)-β-diketonate complex, cis-[Ru(tfnb)(dppm)₂]PF₆ (Ru-Naphthyl), was synthesized in good yield and fully characterized by elemental analysis, Fourier-transform infrared spectroscopy, multinuclear nuclear magnetic resonance spectroscopy, and high-resolution electrospray ionization mass spectrometry, confirming the proposed structure. The complex exhibited selective cytotoxicity toward PC-3 prostate cancer cells, with an IC₅₀ value of 14.19 μM, whereas lower toxicity was observed in non-tumoral PNT-2 cells (IC₅₀ = 34.85 μM), resulting in a selectivity index of 2.46. In contrast, neither the non-coordinated ligand nor the ruthenium precursor showed significant cytotoxic activity under the same experimental conditions. Furthermore, the complex markedly reduced clonogenic survival and promoted intracellular reactive oxygen species accumulation, predominantly in tumor cells. Oxidative stress may have been associated with disruption of cell cycle progression, evidenced by a reduced G2/M population and increased sub-G1 events, culminating in apoptotic cell death. Collectively, these findings demonstrate that Ru-Naphthyl exhibits promising antitumor activity against prostate cancer cells through oxidative stress-mediated mechanisms and supports further investigations to elucidate its molecular targets and evaluate its therapeutic potential. 2026-06-30T00:00:00Z https://repositorio.ufu.br/handle/123456789/50005 Title: Effect of poly(D,L-lactic acid), hydroxyapatite, and ozonated saline on the modulation of tissue repair in experimental chronic wounds: an integrated morphological, biochemical, and metabolomic approach Abstract: Chronic wounds are characterized by persistent inflammation, oxidative stress, and impaired tissue repair. This study evaluated poly(D,L-lactic acid) (PDLLA)- and hydroxyapatite (HA)-containing formulations, ozonized saline solution, and their combinations in Wistar rats with experimentally induced impaired wound healing. Two experimental protocols with different induction and treatment durations were investigated. Treatment responses were assessed through macroscopic wound closure, histological and collagen analyses, redox biomarkers, and untargeted metabolomics of plasma and skin tissue. The PDLLA-containing formulation showed the most consistent macroscopic response, with greater wound closure than the Control group. Semi-quantitative histological analysis revealed no statistically detectable differences among groups at the endpoint, whereas ozone-containing treatments were associated with changes in collagen deposition. Redox analyses showed treatment-specific alterations without a uniform response across treatments. Metabolomics revealed distinct treatment-associated profiles, particularly in plasma samples from ozone-containing groups, involving metabolites related to antioxidant, lipid, sphingolipid, amino acid, purine, and energy metabolism. No statistically significant difference between the experimental protocols was detected for the cumulative macroscopic wound-closure response. Overall, the findings suggest that the evaluated treatments produced distinct and outcome-dependent responses, with the PDLLA-containing formulation showing the most consistent association with wound closure and ozone-containing treatments being associated with specific collagen, redox, and metabolic alterations. 2026-08-28T00:00:00Z https://repositorio.ufu.br/handle/123456789/49622 Title: Desenvolvimento de modelo de derme humana bioimpressa em 3D: Estabelecimento de protocolo in vitro e perfil metabólico do uso de bioestimuladores de colágeno Abstract: Gelatin-alginate-based bioinks for 3D bioprinting are widely used due to their inherent advantages, such as biocompatibility, biodegradability, and cell-adhesion properties. While the alginate incorporation addresses the risks that thermal instability poses to post-bioprinting structural fidelity, sustaining long-term hydrogel integrity under cell culture conditions remains a critical challenge. This demands a precise balance between effective crosslinking and the preservation of cell viability. We aimed to enhance the stability of fibroblast-laden gelatin-alginate in vitro using a dual-crosslinking approach, thereby establishing a 3D simplified dermis model to profile the metabolomic signatures of common collagen biostimulators. For this purpose, fibroblast (HFF-1) viability and adhesion were evaluated to determine an optimal, biocompatible crosslinking protocol. Subsequently, metabolites were extracted from both the 3D bioprinted construct and its supernatant. As a result, an effective dual-crosslinking strategy was stablished, consisting of 15 minutes of calcium chloride (CaCl2) 500 mM followed by 15 minutes of 1-Ethyl-3-(3- dimethylaminopropyl)carbodiimide (EDC) 100 mM / N-hydroxysuccinimide (NHS) 20 mM. Construct stability and sustained cell viability were confirmed, enabling accurate metabolomic profiling at 48h in vitro. Notably, calcium hydroxylapatite (CaHA) induced metabolic reprogramming toward a regenerative state, whereas poly(D,L-lactic acid) (PDLA) drove adaptations characterized by sphingolipid remodeling and altered cellmicroenvironment communication. Overall, our dual-crosslinked dermis model demonstrates in vitro stability, providing a validated and effective platform for evaluating the metabolic impact of biomaterials in tissue engineering. 2026-07-17T00:00:00Z https://repositorio.ufu.br/handle/123456789/49456 Title: Análises dos efeitos antiparasitários de complexos metálicos a base de rutênio contra Toxoplasma gondii em células trofoblásticas vilosas humanas Abstract: Congenital toxoplasmosis is a zoonotic disease with a broad global impact, especially affecting populations in situations of socioeconomic vulnerability and with limited access to quality healthcare services. The adverse effects and the inability of current therapies to achieve definitive cure highlight the need for the development of new therapeutic approaches. This study aimed to evaluate, for the first time, the therapeutic potential of two novel ruthenium(II)-based complexes (Ru-fluorophenoxy and Ru-methylphenyl) against Toxoplasma gondii in a congenital context. Ru-fluorophenoxy and Ru-methylphenyl exhibited promising antiproliferative activity, outperforming their non-coordinated ligands and precursor complex, with IC₅₀ values of 4.12 ± 0.59 and 7.0 ± 0.18 µM, respectively. Furthermore, they exhibited variable cytotoxicity, with CC50 values higher than 100 µM for Ru-fluorophenoxy and 14 ± 1.45 µM for Ru-methylphenyl. Ru-fluorophenoxy was selected for further analyses due to its higher selectivity (SI > 24.27). The three selected concentrations (1.5, 3, and 6 µM) of Ru-fluorophenoxy showed predominant effects during the late stages of infection. In addition, Ru-fluorophenoxy demonstrated an irreversible effect at 6 µM, whereas the 3 µM concentration showed a tendency to reverse the reduction, and the 1.5 µM concentration completely reversed the reduction in proliferation. Interestingly, 6 µM of the compound reduced the parasite’s ability to invade new host cells, an effect that was not observed during the first cycle of infection. Thus, this study demonstrated significant antiparasitic effects of Ruthenium(II) metal complexes against Toxoplasma gondii in congenital toxoplasmosis. Notes: Agradeço à Universidade Federal de Uberlândia (UFU) pelo apoio concedido. Este trabalho foi financiado pela Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), por meio do auxílio APQ-02468-23, e pelo Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), por meio da bolsa/processo nº 302523/2025-1. Além disso, o presente trabalho também foi realizado com o apoio da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Código de Financiamento 001. 2026-07-10T00:00:00Z