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Item type: Item , Melatonin modulates behavioral and physiological responses in a concentration-dependent manner in a pilocarpine-induced seizure-like model using zebrafish larvae(2026) Valadares, Lorranny Pereira de Assis; Sousa, Bianca Leite Carnib de; Roque, Bruno dos Santos Ferreira; Cirqueira, Felipe; Rocha, Thiago Lopes; Machado, Mônica Rodrigues Ferreira; Miguel, Marina PachecoMelatonin has been extensively studied for its antioxidant activity, yet its safety profile and concentration-dependent effects remain only partially understood, particularly in aquatic experimental systems. Here, we investigated the effects of melatonin on behavioral and physiological responses in a pilocarpine (PILO)-induced seizure-like model using zebrafish (Danio rerio) larvae. A multibiomarker framework was employed, combining embryo–larval toxicity assessments up to 144 h post-fertilization with behavioral and biochemical endpoints related to seizure-like activity. Across the tested concentration range (0.14–18 µg/mL), melatonin did not affect mortality or hatching rates. However, exposure to higher concentrations (9.0 and 18 µg/mL) resulted in altered spontaneous contractions and increased embryonic heart rate, indicating measurable physiological changes during early development. At lower concentrations (2.25 and 4.50 µg/mL), melatonin was associated with reduced PILO-induced hyperlocomotion, increased latency to seizure-like onset, and reduced progression to more severe behavioral stages. These responses were accompanied by a reduction in reactive oxygen species (ROS) levels at both 72 and 144 hpf. Collectively, the data reveal a concentration-dependent response profile, with distinct behavioral and physiological outcomes emerging across exposure levels. This study contributes to the characterization of melatonin effects in zebrafish larvae and underscores the importance of dose selection in experimental seizure models.Item type: Item , Drug repurposing for experimental neurocysticercosis: in vitro and in vivo evaluation of nanoformulated triclabendazole(2026) Souza, Jéssica Yonara de; Rocío Bedogni, Giselle; Freitas, Ana Luiza Pereira de; Campos, Geovana Batista de; Alves, Wellington David Luz; Costa, Tatiane Luiza da; Vinaud, Marina Clare; Javier Salomon, ClaudioCurrent pharmacological treatment of neurocysticercosis relies primarily on albendazole; however, despite its efficacy, its clinical use is limited by treatment-associated inflammatory complications. In this context, drug repurposing combined with nanotechnology-based drug delivery systems represents a promising strategy to improve therapeutic outcomes. Thus, the potential repurposing of triclabendazole, the benzimidazole drug of choice for fascioliasis, was investigated by assessing the metabolic effects of its nanoformulation in an experimental model of neurocysticercosis. Triclabendazole nanoparticles stabilized with poly(vinylpyrrolidone) were prepared by spray drying and characterized in terms of production yield, particle size, zeta potential, polydispersity index, Fourier-transform infrared spectroscopy, X-ray diffraction, in vitro drug release, and hemocompatibility. The spray-drying process achieved production yields ranging from 75% to 81%. Particle size increased from approximately 100–220 nm before drying to 300–400 nm after redispersion of the dried powder. Physicochemical analyses demonstrated that triclabendazole was predominantly present in an amorphous state within the nanosystem. In vitro dissolution studies showed a marked enhancement in drug release compared with the raw drug, while hemolysis assays confirmed acceptable hemocompatibility. In vivo metabolomic evaluation of Taenia crassiceps cysticerci following treatment with the nanoformulation revealed significant alterations in metabolic pathways associated with energy production and parasite survival, indicating a profound disruption of parasite metabolism. To our knowledge, this is the first study demonstrating the potential of nanoformulated triclabendazole as a repurposed therapeutic strategy for neurocysticercosis while providing mechanistic evidence of its effects on parasite metabolism.Item type: Item , Microencapsulated oxfendazole modulates neuroinflammation in experimental Taenia crassiceps neurocysticercosis(2026) Moura, Anna Clara Lopes de; Rocío Bedogni, Giselle; Campos, Geovana Batista de; Souza, Jéssica Yonara de; Gomes, Rodrigo Saar; Lino Júnior, Ruy de Souza; Javier Salomon, Claudio; Vinaud, Marina ClareNeurocysticercosis (NCC), caused by the larval stage of Taenia solium, is the leading cause of acquired epilepsy in developing countries and an increasing public health concern in developed regions. Albendazole (ABZ) and praziquantel are the mainstays of current treatment, but their effectiveness is constrained by their poor absorption in the central nervous system and the worsening of inflammatory reactions after parasite degeneration. This neuroinflammation brought on by the medication poses a serious safety risk. Thus, this study aimed to evaluate the immunomodulatory and histopathological effects of oxfendazole microparticles (OXF-MICRO) in a murine model of Taenia crassiceps NCC. BALB/c mice intracranially infected with cysticerci were treated 30 days post-infection with a single oral dose of ABZ (40 mg/kg), conventional oxfendazole (OXF, 30 mg/kg), or OXFMICRO (30 mg/kg). Brain cytokine levels were quantified 24 h post-treatment using cytometric bead array, and histopathological analyses were performed. All treatments induced cyst degeneration and significantly reduced TNF-α, IL-17, and IL-10 levels, indicating disruption of parasite-induced immune tolerance. Distinct immune profiles were observed: OXF promoted a Th1-type response (increased IFN-γ and IL-2), whereas OXFMICRO and ABZ induced a Th2-skewed response (elevated IL-4). Notably, only OXF-MICRO significantly reduced polymorphonuclear cell infiltration in brain tissue (p = 0.029). These findings demonstrate that OXFMICRO preserves antiparasitic efficacy while attenuating acute inflammatory infiltration, suggesting an improved safety profile. Collectively, these results support microencapsulation as a promising strategy to enhance therapeutic outcomes in NCC.Item type: Item , Vascular hyporesponsiveness in sepsis is associated with nitric oxide-dependent activation of G-protein receptor kinase 2(2026) Abbud, Daniela Dal Secco; Olivon, Vania Claudia; Celes, Mara Rubia Nunes; Crestani, Sandra; Akinaga, Juliana; Lima, Vanessa; Corrêa, Thiago; Pupo, André Sampaio; Cunha, Fernando de Queiroz; Sordi, Regina de; Assreuy, JamilSepsis is a life-threatening condition caused by a dysregulated host response to infection that often leads to profound end organ derangement in which vascular system dysfunction plays a critical role. Septic shock is characterized by a pronounced decrease in peripheral vascular resistance, progressive hypotension, and lack of response to vasoconstrictors. We have previously shown that sepsis induced cardiac hyporesponsiveness to isoproterenol by a nitric oxide (NO)-dependent mechanism, mediated by increased G-protein receptor kinase 2 (GRK2) expression and receptor phosphorylation. In the present report, we investigated whether this mechanism is relevant in the vascular system. The contractile response of aortic rings and the in vivo responsiveness to phenylephrine were significantly reduced in septic mice at both 12 and 24 hours after cecal ligation and puncture surgery. Higher expression of GRK2 and increased phosphorylated GRK2 were detected in the aorta of septic mice along with a reduction in the density of alpha-1 adrenergic receptors. Treatment with the selective NOS-2 inhibitor 1400 W prevented vessel hyporesponsiveness, abolished GRK2 expression and activation and preserved alpha-1 adrenergic receptor density. Naïve mouse aorta rings incubated with a NO donor displayed diminished contractile response, and this effect was prevented by a GRK2 inhibitor. Our study showed that during sepsis, NOS-2-derived NO induces and activates GRK2, leading to alpha-1 adrenergic receptor internalization and hyporesponsiveness to vasoconstrictors. Therefore, our findings suggest that GRK2 inhibition is a potential new therapeutic target in sepsis-induced vascular dysfunction.Item type: Item , Cellular immune response of Amblyomma sculptum and Amblyomma americanum to entomopathogenic fungi: implications for biological tick control(2026) Silva, Cárita de Souza Ribeiro e; Lima, Valesca Henrique; Pinto, Salorrane Miranda do Nascimento; Sandes, Gustavo Felizardo Santos; Costa, Victor Hugo Ribeiro; Mulenga, Albert; Oliva Chavez, Adela Sarahi; Fernandes, Éverton Kort KampAmblyomma spp. (Acari, Ixodidae) serve as primary vectors for numerous pathogens affecting humans and animals. Unlike other arthropods, ixodid ticks exhibit notably less susceptibility to entomopathogenic fungi, which are widely used as biological control agents. This study aimed to determine whether the dynamics of the cellular immune response to fungal infection differ between Amblyomma sculptum and Amblyomma americanum. Engorged female ticks were treated with conidial suspensions of Metarhizium robertsii ARSEF 2575 or Beauveria bassiana ARSEF 9588. For the survival assay, ticks were immersed in suspensions of 5 108 conidia mL1 . Inoculation with 5 107 conidia mL1 was used in assays to evaluate immune responses. Haemolymph was collected 24 h post-treatment, and smears were prepared for microscopy-based characterization of haemocyte responses. Confocal and fluorescence microscopy were used to classify, quantify and visualize the haemocyte types, including granulocytes, plasmatocytes, prohaemocytes, oenocytoids and spherulocytes. Our findings reveal that plasmatocytes dominate the haemocyte population in A. sculptum, whereas granulocytes are predominant in A. americanum, both showing reduced concentrations following B. bassiana exposure. Prohaemocytes and oenocytoids were present in all groups but at lower frequencies. Additionally, B. bassiana was more effective against A. sculptum, whereas M. robertsii exhibited greater efficacy against A. americanum, with phenoloxidase activity of 29%. This study provides crucial insights into the cellular immune defences of Amblyomma ticks and highlights potential fungal strains that may overcome tick antifungal susceptibility. These findings establish a foundation for future research on haemocyte-mediated immunity in ixodid ticks, a topic with limited existing literature and contribute to the development of targeted biological control strategies.