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Efeitos da azitromicina no sistema nervoso central em modelo de kindling induzido por pentilenotetrazol em camundongos

2026-01-01T00:00:00Z

Título: Efeitos da azitromicina no sistema nervoso central em modelo de kindling induzido por pentilenotetrazol em camundongos Autor(es): Santiago, Rodrigo Maia Abstract: Epilepsy is characterized by neuronal hyperexcitability and is associated with redox imbalance, which supports the investigation of drugs capable of modulating seizure outcomes and oxidative-nitrosative biomarkers. The effect of azithromycin (AZT) on the seizure phenotype and redox axis was evaluated in pentylenetetrazole (PTZ)-induced models in mice. An experimental, controlled, in vivo study was conducted, comprising an acute and a chronic model. In the acute model, AZT was administered intraperitoneally at doses of 100 or 200 mg/kg, followed by a challenge with 85 mg/kg PTZ to record the latencies to the first seizure and death. In the chronic model, PTZ-kindling (35 mg/kg on alternate days for 21 days) was used, with behavioral assessment using the Racine Scale. At the end of the protocols, reduced glutathione (GSH), nitrite, and thiobarbituric acid reactive substances (TBARS) were quantified in the prefrontal cortex, hippocampus, and striatum. A dual effect, dependent on dose and exposure time, was observed. In the acute model, AZT 100 mg/kg reduced the latency to the first seizure (median of 36 s vs. 49 s in the control), while AZT 200 mg/kg prolonged the time to death (median of 200 s vs. 173 s in the control). Biochemically, the acute phase was marked by a nitrosative peak, with a significant increase in nitrite across the three regions evaluated at the 200 mg/kg dose (p < 0.01). In the chronic model, the 200 mg/kg dose transiently attenuated seizure severity (median score 3.0 vs. 4.0 in the control; p = 0.0407 on day 13), whereas the 100 mg/kg dose was associated with high mortality and the maintenance of high scores (median between 4.0 and 5.0). In contrast to the acute phase, no statistically significant changes were detected in the redox panel (p > 0.05 for GSH, nitrite, and MDA) at the end of the kindling protocol, suggesting late biochemical adaptation or buffering. It was concluded that AZT acted as a complex and non-linear modulator in the central nervous system, with manifestations ranging from excitatory facilitation and transient behavioral attenuation to acute nitrosative induction, diverging from the profile of a classic and uniform neuroprotective agent. Tipo: Dissertação

Mo-CBP3-PepIII altera o perfil proteômico de células de câncer gástrico, induz a formação de poros na membrana e o acúmulo excessivo de ROS

2026-01-01T00:00:00Z

Título: Mo-CBP3-PepIII altera o perfil proteômico de células de câncer gástrico, induz a formação de poros na membrana e o acúmulo excessivo de ROS Autor(es): Oliveira, Talia Rabelo Abstract: Plant-derived peptides have gained prominence due to the possibility of structural modifications and selective toxicity. Moringa oleifera gave rise to the peptide Mo-CBP3-PepIII, which was synthesized to achieve greater selectivity. Initially, it was investigated for its antimicrobial and antifungal activities; therefore, the promising results led to further analyses regarding its antitumor potential. In this study, its activity against gastric adenocarcinoma cells (AGS) was evaluated, demonstrating low toxicity toward normal gastric mucosal cells (MNP-01). The mechanism of action of the synthetic peptide was investigated. First, cytotoxicity analysis was performed to determine the IC₅₀ value, followed by the evaluation of membrane integrity, accumulation of reactive oxygen species, morphological alterations by scanning electron microscopy, and proteomic analysis. Proteomic profiling revealed that the peptide modulated proteins involved in proliferation, metabolism, cytoskeletal organization, stress response, cellular repair, and drug resistance. A reduction in the expression of pro-tumoral proteins essential for cancer development and survival was observed, while an increase in the abundance of some tumor suppressor proteins was detected. The peptide promoted increased cellular vulnerability to oxidative stress, an important mechanism in tumor cell lysis. Proteomic analysis highlighted a reduction in proteins highly associated with resistance to several therapies, such as CLIC1 and HNRNPC, whose downregulation is related to decreased resistance to cisplatin, oxaliplatin, and vincristine. Conversely, some proteins showed increased abundance, including TXNL1, which contributed to reduced resistance to cisplatin. These findings indicate a gastric antitumor effect with a multifaceted mechanism of action, involving increased membrane permeability, pore formation, and dysregulation of multiple intracellular pathways, suggesting that Mo-CBP3-PepIII is a promising therapeutic candidate, either alone or in combination with conventional drugs. Therefore, future studies should further elucidate its effects on apoptosis, migration, tumor invasion, and associated signaling pathways, as well as deepen the investigation of the proteins identified in this study to better understand their roles in tumor biology and the potential interaction of Mo-CBP3-PepIII with conventional chemotherapeutic agents. Tipo: Dissertação

Análise do perfil ultraestrutural e molecular das linhagens MNP-01 e AGP-01: identificação de biomarcadores associados ao fenótipo maligno no câncer gástrico

2026-01-01T00:00:00Z

Título: Análise do perfil ultraestrutural e molecular das linhagens MNP-01 e AGP-01: identificação de biomarcadores associados ao fenótipo maligno no câncer gástrico Autor(es): Vieira, Antônia Catarine Gomes Abstract: Gastric cancer (GC) is a global public health challenge, ranking fifth in both incidence and mortality among malignant neoplasms. Its development is multifactorial, involving genetic, epigenetic, biochemical, and morphological alterations. Considering the scarcity of studies in Brazilian populations, this study aimed to compare the ultrastructural and molecular profiles of the gastric cell lines MNP-01 (non-tumoral) and AGP-01 (tumoral), in order to prospect protein biomarkers associated with the malignant phenotype. Ultrastructural and nanomechanical parameters were evaluated by AFM, while protein and other biomolecule profiles were analyzed by shotgun proteomics (UHPLC-MS/MS) and Raman spectroscopy, respectively. AFM maps revealed differences in the cell surface: the tumor cell line AGP-01 exhibited lower roughness, tumor volume, and surface area, as well as greater deformability and reduced Young’s modulus and adhesion values. In turn, Raman spectroscopy revealed differences in the vibrational profile as well as a distinct molecular composition, including nucleic acids, lipids, and proteins. Proteomics identified 2,209 proteins, of which 433 were exclusive to the MNP-01 lineage, 328 to the AGP-01 lineage, and 724 shared between both. From this total, proteins involved in protein synthesis and translation, oxidative stress and metabolism, cell cycle regulation, cell adhesion, drug resistance, and cytoskeletal reorganization were highlighted. Protein interaction and functional analyses indicated alterations in oncogenic pathways, especially AKT/mTOR, which were confirmed by immunofluorescence. The tumoral lineage AGP-01 showed a significant increase in p-AKT (1.8× vs. MNP-01; p = 0.0289) and p-mTOR (3× vs. MNP-01; p = 0.004), indicating hyperactivation of this pathway as a feature of the malignant phenotype. Altogether, the results demonstrate that the AGP-01 tumor cell line is associated with the integration of ultrastructural alterations, proteomic reprogramming, and activation of pro-survival pathways, broadening the understanding of tumor biology and the biomechanical and molecular bases of metastatic GC, providing support for the identification and investigation of potential therapeutic targets, as well as for future studies with functional validation and translational application. Tipo: Dissertação

Fibrohistiocitoma maligno transplantável em ratos Wistat: caracterização (histopatologia, ultraestrutura, citoquimica enzimática e imunohistoquímica): estudo cinético e aspectos farmacológicos

1987-01-01T00:00:00Z

Título: Fibrohistiocitoma maligno transplantável em ratos Wistat: caracterização (histopatologia, ultraestrutura, citoquimica enzimática e imunohistoquímica): estudo cinético e aspectos farmacológicos Autor(es): Ribeiro, Ronaldo de Albuquerque Abstract: A spontaneous tumor arised on the ragion of salivar gland C-TEGS-2047) of a Wistar rat and transplanted with trocarter was studied under several aspects: (a) histologycal characterization Chistopathology, ultrastructure, enzimatic cytochemistry and immunohistochemistry); Cb) metastitic potential; C?) stathnokinetic study using .. Vincristine; (d) Hormonal sensitivity and C-e) search for bioactive substances produced by the tumor. The results showed: Qa) Optical and eletron microscopy studiesCCM and EM) revealed that the tumor is mainly constituted by histiocytic-like cells and also fibroblastic-like cells and undifferentiated celss.The enzymatic cytochemistry was strongly positive —for an a-naphthyl acetate esterase and acid phosphatase, suggesting the histiocytic nature of this neoplasm. Immunohistochemistry study using histiocytic (Lisozyme, a-1-Antitrypsin and a-1 Antichymotrypsin)and intermediate-sized filaments (Vimentin) markers showed activity, only for Lisozyme and • Vimentin confirming the fibrohistiocytic. nature of the tumor and suggesting that it may be considered as a malignant fibrous histipcytoma CMFH). Tipo: Dissertação