REPOSITÓRIO INSTITUCIONAL DA UNIVERSIDADE DO VALE DO PARAÍBA
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Submissões Recentes
Photodynamic therapy: challenges and innovations for treating cancer
(Frontiersin) Silva, Newton Soares da; Ferreira-Strixino, Juliana; Soares, Cristina Pacheco
Antitumor activity of membranes associated with Acmella oleracea extract
(Associação Brasileira de Divulgação Científica) Silva, Carlos Augusto Priante da; Godoi, Bruno Henrique; Menegon, Renato Farina; Silva, Newton Soares da; Soares, Cristina Pacheco
Epithelial cancers, such as epidermoid cancer and some adenocarcinomas, affect surface areas that are generally more accessible to various treatments. However, this group of tumor cells has an aggressive behavior, leading to a high annual mortality rate. The development of a biomaterial that is non-invasive, can kill tumor cells, and prevent opportunistic infections is the basis for the treatment for this type of cancer. Therefore, the objective of this study was to develop a biomaterial from chitosan and A. oleracea extracts that exhibits cytotoxic action against the HEp-2 tumor cell line. Dried crude 90% ethanol extracts were obtained through ultrasound-assisted maceration, followed by liquid-liquid extraction to yield the butanol fraction. From these extracts, chitosan membranes were developed and evaluated for their antitumor activity against HEp-2 using viability tests with crystal violet and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, in addition to a wound healing test. The cytotoxic assays indicated a significant reduction in cell density and mitochondrial activity, especially at the concentration of 1000 mg/mL of crude extract. The butanol fraction had minimal effects on mitochondrial activity. The wound healing test demonstrated that the biomaterial and extract prevented closure of the wound created in the cell monolayer within 48 h of incubation and caused changes in cell morphology. In view of this, we concluded that a chitosan membrane associated with a 90% ethanol extract of Acmella oleracea exhibited cytotoxic activity is a potential alternative treatment for superficial cancers.
3D-bioprinted model of adult neural stem cell microenvironment in Alzheimer’s disease
(ACCSCIENCE Publishing) Ferreira, Natalia Dall’Agnol; Ferreira, Paula Scanavez; Soares, Cristina Pacheco; Porcionatto, Marimelia Aparecida; Salles, Geisa Rodrigues
Neurogenesis plays a major role in neuroplasticity and memory. In adult human and mouse brains, neural stem cells (NSCs) are mainly distributed in two extensively characterized neurogenic niches: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricles. Impaired neurogenesis is one of the consequences of Alzheimer’s disease (AD), contributing to cognitive decline and progressive memory loss. Developing new in vitro models that resemble this three-dimensional (3D) structure is fundamental for enhancing our understanding of the SVZ neurogenic niche dynamics in AD. Herein, we produced and characterized a 3D-bioprinted model of the adult SVZ neurogenic niche containing amyloid β (Aβ) oligomers, mimicking the NSC microenvironment in AD. In this model, Aβ oligomers induce oxidative stress and reduce the proliferative potential of NSCs, while stimulating neuronal differentiation. We hypothesize that these events are an early attempt of adult NSCs to compensate for neuronal death in AD pathogenesis. Our 3D model simulates the NSC niche physiology, reproducing an early response of NSCs in AD, strengthening the importance of studying the potential of neurogenesis in neurodegeneration.
2D and 3D Models of Alzheimer’s Disease: Investigating Neuron-like Cells in Oxidative Environments
(ACS Publications) Salles, Geisa Rodrigues; Giraldi, Luiza de Andrade; Silva, Newton Soares da; Porcionatto, Marimelia Aparecida; Soares, Cristina Pacheco
Alzheimer’s disease (AD) is a complex and enigmatic neurodegenerative disorder in which amyloid-β (Aβ) aggregates and oxidative stress play crucial roles in neuronal damage. Aβ forms senile plaques, while reactive oxygen species (ROS)-induced oxidative stress causes cellular dysfunction. Elucidating neuronal injury led by mild and severe oxidative stress may provide insight into how neurons respond to toxic environments. In parallel, modeling AD three-dimensionally is in the spotlight, sustainably
contributing to reducing animals in research and replicating spatially neuronal mechanisms, such as neurite network and oxidative stress responses. This study evaluates the effects of oxidative stress on neuron-like cells cultured in two-dimensional (2D) and 3D spheroids, strengthening their potential as platforms for AD investigation. For the 2D models, SH-SY5Y (cells from human neuroblastoma) cells were differentiated into the neuronal phenotype and exposed to mild or severe concentrations of oxygen peroxide (H2O2, 100 or 200 μM, respectively). Cytoviability, ROS, Aβ particle analyses, and morphological aspects were assessed. Neuronal cells under severe stress produced elevated levels of intra- and extracellular Aβ aggregates. A range of Aβ particle analyses were performed comparing their properties, and morphologically, neurites were compromised under severe stress. For the 3D models, SH-SY5Y spheroids were self-assembled by 10 days of cultivation on developed nonadhesive hydrogel microwells and differentiated into the neuronal phenotype; their area, circularity, and solidity were measured. Spheroids were exposed or not to 200 μM H2O2, stained for cytoskeleton/nuclei, and imaged by scanning electron microscopy (SEM), and their viability was evaluated. Throughout the cultivation period, spheroids grew and differentiated morphologically. Neurite distribution was observed along the 3D composition; however, under oxidative stress, cytoviability decreased, abnormal nuclear staining was observed surrounding the spheroids, and morphological disorganization was evident by SEM, representing structural disarrangement and nuclear disruption. Briefly, this study provides a basis for exploring oxidative stress and producing robust 3D approaches to unraveling AD mechanisms.
Methylene blue functionalized ZnO nanoparticles: a promising approach for photodynamic therapy in the treatment of leishmaniasis
(Sage) Gouvea, Thainara Alves; Ambrósio, Jéssica Aparecida Ribeiro; Carvalho, Janicy Arantes; Marmo, Vitor Luca Moura; Marcolino, Luciana Maria Cortez; Pinto, Juliana Guerra; Ferreira-Strixino, Juliana; Simioni, Andreza Ribeiro; Gonçalves, Erika Peterson
Zinc oxide (ZnO) has wide application in engineering, but its use in medical sciences has aroused growing interest. In this context, ZnO nanoparticles were investigated as vehicles for the delivery of methylene blue (MB), a photosensitizer (PS) used in photodynamic therapy (PDT) against Leishmania braziliensis. ZnO-NPs were produced by a coprecipitation method and characterized by several techniques, including scanning electron microscopy (SEM), UV-VIS spectroscopy, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The results showed that the ZnO-NPs presented uniform spheroidal morphology with open porosity, allowing an efficient methylene blue (MB) encapsulation without significant structural changes, ensuring stability and the absence of aggregation. The PS was adsorbed on the porous surface of the ZnO nanoparticles, characterized by scanning electron microscopy (SEM) and steady-state analysis techniques. Spectroscopic analysis confirmed the maintenance of the photosensitizing properties of MB. The biological activity was evaluated in vitro using the trypan blue exclusion method in macrophages infected with Leishmania braziliensis. After loading with the photosensitizer, they maintained their photophysical properties, ensuring the proper location of the dye within the cells. In vitro assays demonstrated the internalization of ZnO/MB-NPs by infected macrophages and a significant reduction in parasite viability after light activation. Thus, the results showed that the developed system exhibits a promising photodynamic activity with relevant therapeutic potential in treating macrophages infected by Leishmania braziliensis.