Ingrid Gracielle Martins da Silva

Background/Objectives: American trypanosomiasis, caused by Trypanosoma cruzi, remains a major public health challenge due to the limited efficacy and adverse effects associated with current treatments. Octyl gallate (OG), a semi-synthetic derivative of gallic acid, has demonstrated promising biological activities, including antiparasitic effects. Methods: The in vitro trypanocidal activity of OG was evaluated against T. cruzi. Mechanism of action studies included the inhibition of the trypanothione reductase enzyme and flow cytometry assays to measure cell death pathways (propidium iodide uptake). Additionally, the immunomodulatory potential of the compound was investigated by assessing cytokine production and innate immune responses. Results: In this study, the trypanocidal activity of OG against different evolutionary forms of T. cruzi was investigated. Using MTT-based viability assays, OG exhibited significant activity against epimastigotes (IC50 = 5.92 ± 0.47 µM), trypomastigotes (EC50 = 3.20 ± 0.14 µM), and intracellular amastigotes (EC50 = 4.07 ± 0.72 µM). The compound also demonstrated favorable selectivity indices, particularly against trypomastigotes and amastigotes, indicating selective toxicity toward the parasite compared to mammalian host cells. In infected macrophages, OG increased TNF-α and IL-12 production while reducing IL-10 and IL-6 levels, in addition to stimulating reactive oxygen species (ROS) and nitric oxide (NO) production, suggesting an immunomodulatory effect that contributes to parasite control. Molecular docking analyses revealed a favorable interaction between OG and trypanothione reductase (TR), while biochemical assays demonstrated reduced NADPH consumption, indicating interference with TR activity. Ultrastructural analysis revealed severe morphological alterations, including membrane disruption, cytoplasmic disorganization, mitochondrial swelling, and features consistent with apoptosis-like cell death. Conclusions: Collectively, these findings demonstrate that OG exhibits potent and selective trypanocidal activity associated with immunomodulatory effects, ultrastructural damage, and disruption of parasite redox metabolism through TR inhibition, supporting its potential as a candidate for future preclinical studies against Chagas disease.

This study aimed to evaluate the effects of an ethanolic extract from Punica granatum L. (EE-PG) on bovine ovarian tissue vitrification, focusing on follicular morphology, ultrastructure, stromal cell density, collagen distribution, redox status, and mRNA expression of antioxidant-related genes. Bovine ovarian cortex fragments were divided into a fresh control group for in vivo tissue evaluation or vitrified either with the base vitrification solution (αMEM) alone or supplemented with different concentrations of EE-PG (10, 50, and 100 µg/mL), and subsequently stored in liquid nitrogen for 5 days. After warming, fragments were allocated for morphological and oxidative stress analyses or incubated for 24 h to resumption of cellular metabolism. The concentrations of 10 and 100 µg/mL preserved follicular morphology immediately after warming, and were therefore selected for ultrastructural evaluation. Both concentrations mitigated vitrification-induced damage. Gene expression analysis showed decreased levels of catalase (cat), Glutathione Peroxidase 1 (gpx1), and Nuclear Factor Erythroid 2-Related Factor 2 (nrf2) compared with the fresh control, whereas Superoxide Dismutase (SOD) enzymatic activity increased after incubation with 10 µg/mL EE-PG compared with all experimental groups. Moreover, Malondialdehyde (MDA) levels in tissues treated with 10 or 100 µg/mL were comparable to fresh controls after incubation. Overall, EE-PG at 10 or 100 µg/mL in the vitrification solution supported the maintenance of tissue morphology, redox balance—despite the downregulation of essential antioxidant genes, which may be associated with a reduced demand for enzymatic antioxidant defense—and cellular metabolism, indicating potential for improving bovine ovarian tissue vitrification outcomes.

Chagas disease remains a significant neglected tropical disease that predominantly affects vulnerable populations in rural, low-income areas of Latin America. The management of this condition is severely hindered by the limitations of current therapies, which are characterized by substantial toxicity, diminished efficacy during the chronic phase, and the emergence of parasitic resistance. Given the promising activity of SB-83 (a 2-aminothiophenic derivative) against Leishmania spp., the present study sought to evaluate its trypanocidal activity against Trypanosoma cruzi. The results showed that SB-83 exhibited potent inhibitory effects on the epimastigote forms of T. cruzi (IC₅₀ = 6.23 ± 0.84 μM), trypomastigotes (EC₅₀ = 7.31 ± 0.52 μM) and intracellular amastigotes (EC₅₀ = 5.12 ± 0.49 μM). Furthermore, the cellular proliferation assay results indicated CC₅₀ values of 77.80 ± 2.05 µM for LLC-MK2 CCL-7 and 24.21 ± 1.2 µM for Vero CCL-87, with a selectivity index above 10 for LLC-MK2 cells. In addition, the compound increased TNF-α, IL-12, nitric oxide, and ROS while decreasing IL-10. Moreover, in silico and in vitro assays confirmed its binding to trypanothione reductase, disrupting redox balance. Flow cytometry further revealed apoptosis induction in trypomastigotes, whereas electron microscopy showed cellular disruption and organelle disorganization. Therefore, SB-83 demonstrated potent activity against the TcI-resistant strain linked to Chagas cardiomyopathy at non-toxic concentrations for host cells, supporting its potential as a therapeutic candidate.

Background: Surface contamination in healthcare environments plays a key role in the persistence and transmission of microorganisms. Long-lasting antimicrobial coatings based on copper–polymer complexes offer a promising passive strategy to minimize environmental contamination and healthcare-associated infections. Methods: This study evaluated a copper-alloy polymeric tape through physicochemical, in vitro, and hospital-based assessments. Structural analyses (XRD, Raman, SEM, EDX) were used to characterize the material, while antimicrobial efficacy was determined against Gram-positive and Gram-negative bacteria following ISO 22196:2011. A randomized 19-week clinical study was conducted in the Emergency and Urgent Unit of the University Hospital of Brasília to quantify microbial loads on high-touch surfaces covered with the copper-alloy tape or a non-antimicrobial control. Results: Structural characterization techniques validated the integrity and heterogeneous distribution of copper within the polymeric matrix. All tested bacterial strains exhibited complete growth inhibition on the copper-alloy tape, with final counts consistently below the detection threshold (Candida parapsilosis was the most frequently identified species. Conclusions: These findings support its use as a sustainable intervention to reduce environmental contamination and infection risks in healthcare settings.

Oxidative stress compromises follicle survival during in vitro culture. Natural antioxidants may reduce cellular damage and preserve tissue integrity. This study evaluated the ethanolic extract from Punica granatum L. (EE-PG) on bovine ovarian tissue cultured in vitro. Bovine ovarian (n = 24) fragments were cultured for 6 days in αMEM⁺ medium with or without EE-PG at 10, 50, or 100 µg/mL. At the end of the in vitro culture, the medium was used to evaluate antioxidant capacity (DPPH and ABTS assays), while the fragments were collected for morphological and biochemical analyses. HPLC-UV-Vis confirmed the presence of α-punicalagin in the pure EE-PG. At 100 µg/mL, EE-PG showed the strongest effects: it had higher antioxidant capacity, preserved follicle morphology and ultrastructure, and promoted follicle activation. At 50 and 100 µg/mL, the extract also reduced malondialdehyde (MDA) and increased thiol levels, indicating protection against lipid peroxidation. In contrast, 10 µg/mL had little effect. Follicle and oocyte diameters were not significantly altered, but the collagen I/III ratio increased at higher concentrations, suggesting extracellular matrix remodeling. Together, these findings demonstrate that EE-PG protects bovine preantral follicles from oxidative stress, maintains redox balance, and preserves tissue integrity. These results reinforce the potential of Punica granatum L. extract as a natural antioxidant in reproductive biotechnologies and fertility preservation.

Breast cancer is the second most prevalent type of cancer worldwide and the leading cause of cancer-related mortality among women. Despite substantial advancements in scientific research, cancer continues to pose a major challenge due to its high global incidence. While numerous nontargeted therapies have been developed, nanotechnology-based platforms are emerging as a promising future for cancer treatment. In this context, we investigated the in vitro antitumor activity of citrate-coated copper oxide nanorods (CuO-nr, aspect ratio ∼3) against breast cancer cells. The CuO-nr colloids demonstrated stability for over 120 days under ambient conditions, with an average hydrodynamic diameter of 107.1 ± 0.67 nm and a zeta potential of -23.8 ± 1.87 mV. Cell viability assays showed that CuO-nr were minimally harmful to nontumor fibroblast cells but highly cytotoxic to MCF-7 breast cancer cells. Flow cytometry analysis suggested that early apoptosis may be the primary mechanism of cell death induced by these nanoparticles. Furthermore, significant alterations in cell morphology were observed through scanning electron microscopy. These findings indicate that citrate-coated CuO-nr possess effective antitumor activity and hold promise as potential agents for targeted cancer therapy.

Background: Paullinia cupana Kunth, popularly known as guarana, a native Amazonian shrub cultivated by the Sateré-Mawé ethnic group, has been used in traditional medicine for various purposes, including stimulant and therapeutic actions, due to its chemical composition, which is rich in bioactive compounds. This study explored the reductive potential of guarana with nanobiotechnology and aimed to synthesize silver nanoparticles (AgNPs) using the aqueous extract of leaves collected during the dry and rainy seasons, assessing their biological and catalytic activities. Methods: The AgNPs were synthesized in a water bath at 70 °C for three hours and then characterized using techniques such as UV-Vis spectroscopy, DLS, zeta potential, MET, NTA, and EDX and had their effects on various biological systems assessed in vitro, as well as in catalytic tests aimed at indicating the probable influence of the time when the plant material was collected on the properties of the nanostructures. Results: The AgNPs had an average diameter between 39.33 and 126.2 nm, spherical morphology, absorption bands between 410 and 450 nm, and high colloidal stability over two years. The biological results showed antibacterial activity against all the species tested, as well as remarkable antioxidant action against DPPH and ABTS free radicals, in the same way as the aqueous leaf extracts of P. cupana, in addition to cytotoxic properties against cancerous (A431 and A549) and non-cancerous (HaCaT and HNTMC) cells. The AgNPs were active against promastigote forms of Leishmania (Leishmania) amazonensis while not affecting the viability of macrophages, and from the LC₅₀ and LC₉₀ values, the AgNPs were more effective than the metal salt solution in controlling Aedes aegypti larvae and pupae. We also reported that the catalytic degradation of the organic dyes methylene blue (MB) and methyl orange (MO) by AgNPs was over 90% after 40 or 14 min, respectively. Conclusions: Thus, our results support the potential of seasonal extracts of guarana leaves to produce AgNPs with diverse application possibilities for the health, industrial, and environmental sectors.

Background/Objectives: Curcumin has antimicrobial activity, and its mechanism of action involves changing histone acetylation. Our group has shown that histone deacetylases (HDACs) inhibitors increase the sensibility of Cryptococcus neoformans to certain antifungal treatments. Therefore, the aim of this work was to investigate whether curcumin pretreatment increases the effect of photodynamic therapy (PDT) mediated by aluminum phthalocyanine in nanoemulsion (AlPc-NE) against C. neoformans. Methods: The minimum inhibitory concentrations (MIC) of AlPc-NE and curcumin, along with the 72-h growth curve of cells exposed to the combined treatments, were evaluated in the C. neoformans reference strain H99. Additionally, further analysis was performed using HDAC gene deletion mutant strains, hda1Δ and hos2Δ. Results: Curcumin reduces the effect of PDT on C. neoformans reference strain H99, likely due to its antioxidant properties. In the hda1Δ strain, 50% MIC of curcumin reduced the effect of PDT, but this effect was not observed in response to 75% MIC of curcumin. Conversely, in the hos2Δ strain, pretreatment with curcumin at 75% MIC enhanced the efficacy of PDT in combination with 50% MIC of AlPc-NE. Conclusions: These results indicate that curcumin inhibits C. neoformans. Moreover, at lower concentrations, curcumin protects cells against oxidant damage, while at higher concentrations, it may trigger epigenetic mechanisms that compromise cell viability. In conclusion, both curcumin and PDT are active against C. neoformans, with HDACs affecting their efficacy, and the effectiveness of the combined treatment depends on the concentration of both curcumin and AlPc-NE.