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Nanoplásticos de poliestireno como moduladores do eixo microbiota-intestino-cérebro: implicações na disbiose e no estresse oxidativo em camundongas em diferentes fases do desenvolvimento

Thu, 01 Jan 2026 00:00:00 GMT

Título: Nanoplásticos de poliestireno como moduladores do eixo microbiota-intestino-cérebro: implicações na disbiose e no estresse oxidativo em camundongas em diferentes fases do desenvolvimento Autor(es): Lima, Júlia Grombone de Vasconcellos Abstract: The environmental dissemination of micro- and nanoplastics (MNPs) has raised growing concerns regarding their impact on human health and the integrity of the microbiota-gut-brain axis. This study evaluated the effects of repeated oral exposure to polystyrene nanoplastics (100 nm, 40 mg/kg) over 21 days in late young (n=16) and pre-pubertal (n=15) female Swiss mice. Two cohorts underwent a battery of behavioral tests, including the Open Field Test and Forced Swim Test. Following euthanasia, fecal samples were collected for microbiota analysis via qPCR, and brain tissues—specifically the hippocampus (HP), prefrontal cortex (PFC), and striatum (STR)—were harvested to quantify biomarkers of oxidative and nitrosative stress. The results demonstrated that while there were no alterations in global locomotion or classical anxiety- and depression-like behaviors, exposed pre-pubertal animals showed a significant increase in peripheral rearing ($p=0.0252$) and grooming ($p<0.05$), indicating an age-dependent selective modulation of exploratory and emotional behavior. Regarding the gut microbiota, no changes were detected in the isolated abundances of Firmicutes or Bacteroidetes; however, a reduction in the Firmicutes/Bacteroidetes ratio was observed in both exposed groups ($p=0.0101$), suggesting the presence of subtle dysbiosis. Distinct vulnerabilities to nitrosative stress were observed according to the life stage: pre-pubertal animals exhibited a robust increase in nitrite levels (p=0.0017), whereas late youngs displayed a compensatory increase in reduced glutathione (GSH) (p=0.0136) within the hippocampus. In conclusion, repeated exposure to nanoplastics promotes low magnitude yet selective effects, with greater neurobehavioral and nitrosative vulnerability during the pre-pubertal stage. These findings provide evidence supporting the involvement of the microbiota-gut-brain axis in the toxicity of these emerging pollutants. Tipo: Dissertação

Avaliação da atividade antimicrobiana da hidralazina frente a Staphylococcus aureus e Candida spp

Mon, 01 Jan 2024 00:00:00 GMT

Título: Avaliação da atividade antimicrobiana da hidralazina frente a Staphylococcus aureus e Candida spp Autor(es): Nascimento, Francisca Bruna Stefany Aires do Abstract: It is estimated that infectious diseases are the leading cause of death worldwide, responsible for approximately 13 million deaths each year. Staphylococcus aureus and Candida spp are among the main human pathogens, related to several infections with different levels of severity. Available treatments are increasingly limited. S. aureus has several virulence factors, in addition to easily acquiring resistance mechanisms. While Candida spp. mainly affects immunocompromised patients, has a small available pharmacological treatment arsenal and is affected by the toxicity fact. The new antimicrobials development is a global urgency and drugs repurposing is the fastest, most economical and safest mechanism. This study aimed to evaluate the antimicrobial activity of hydralazine, in vitro, against clinical strains of S. aureus and Candida spp biofilms, and to evaluate, in silico, the possible action mechanism. By microdilution in broth, the hydralazine minimum inhibitory concentration was determined, which was on average 256 µg/ml against S. aureus. In the tolerance assessment, hydralazine proved to be bactericidal and the association with oxacillin and vancomycin was synergistic in 50 and 25% of the strains, respectively. In evaluating the cell viability of biofilms formed by S. aureus by reducing Methylthiazolyldiphenyltetrazolium bromide (MTT), the sessile minimum inhibitory concentration (50%) ranged from 256 to 2048 µg/ml. Analysis of cell viability by propidium iodide exclusion showed that hydralazine increased non-viable cells (58.78%). In the Comet and TUNEL assays, it was possible to detect breaks and the fragmentation presence in the S. aureus DNA strands. In silico, hydralazine demonstrated greater affinity and the possibility of forming lower energy complexes with the targets S. aureus gyrase complex with DNA (-7.6 kcal/mol), S. aureus gyrase (-7.3 kcal/mol) and S. aureus TyrRS (-7.5 kcal/mol). Biofilms of Candida albicans, C. parapsilosis and C. tropicalis were treated with hydralazine, itraconazole and a combination of these drugs. Reduction in cell viability was assessed by MTT metabolization. Hydralazine (10xMIC) significantly (p≤0.05) reduced the biofilms formed viability. The biofilm formation inhibition was more effective and the MIC of hydralazine for each strain was able to significantly (p≤0.05) reduce biofilm viability. In scanning electron microscopy images, it is possible to see Candida albicans cells damaged by hydralazine. In in silico assays, hydralazine demonstrates more favorable binding energy with targets Exo-B-(1,3)-glucanase (-7.1 kcal/mol) and CYP51 (-7.2 kcal/mol). Therefore, it is concluded that hydralazine has potential to be redirected to the treatment of infections caused by S. aureus and Candida spp., in association with current drugs or alone, acting on planktonic cells and also on biofilms. Tipo: Tese

Investigação do papel das nets (armadilhas extracelulares de neutrófilos) na imunopatogênese da chikungunya

Wed, 01 Jan 2025 00:00:00 GMT

Título: Investigação do papel das nets (armadilhas extracelulares de neutrófilos) na imunopatogênese da chikungunya Autor(es): Leal, Alberto Rubens Siqueira Nogueira Abstract: Neutrophil extracellular traps (NETs) are web-like structures composed of DNA, histones, and antimicrobial proteins released by neutrophils as part of the innate immune response. Although NETs have been extensively studied in bacterial infections, their role in viral diseases, such as Chikungunya virus (CHIKV) infection, remains poorly understood. In viral infections, NETs have an ambiguous role, being able to act as a defense mechanism, but can intensify inflammation and cause tissue damage when released excessively. CHIKV infection causes symptoms such as fever, malaise, rash, myalgia, and especially prolonged arthralgia, which can compromise quality of life. Although it is usually self-limiting, it can lead to death in at-risk groups, such as infants, the elderly, and people with comorbidities. The scarcity of studies on the role of NETs in CHIKV infection compromises the understanding of host defense mechanisms and limits the advancement of more effective therapeutic and diagnostic strategies. This study investigated the presence of NET markers during CHIKV infection over time in female patients. The study included 40 women with CHIKV infection, evaluated on days D0, D21, D90, D180 and D360, and the control group consisted of 10 healthy women. Tipo: Dissertação

Efeito antifúngico do anlodipino em cepas de Candida spp. e em biofilmes mistos com Staphylococcus aureus resistente à meticilina (SARM): avaliação in vitro

Thu, 01 Jan 2026 00:00:00 GMT

Título: Efeito antifúngico do anlodipino em cepas de Candida spp. e em biofilmes mistos com Staphylococcus aureus resistente à meticilina (SARM): avaliação in vitro Autor(es): Queiroz, Helaine Almeida Abstract: Antimicrobial resistance (AMR) has become one of the main threats to global public health, driven by the excessive and inappropriate use of antimicrobials , which favors the emergence and spread of multidrug-resistant strains. In this context, invasive fungal infections caused by Candida yeasts have become a growing problem, with candidemia associated with high mor-tality rates (30-40%). Simultaneously, Methicillin-Resistant Staphylococcus aureus (MRSA) remains an important bacterial pathogen, responsible for infections ranging from skin condi-tions to potentially fatal situations. The management of these infections is even more challen-ging due to the ability of these microorganisms to form biofilms, communities adhered to sur-faces, which offer significant protection and confer antimicrobial tolerance up to a thousand times greater than in planktonic cells. Medical devices, widely used in clinical procedures, re-present environments conducive to the formation of these biofilms, especially when there is colonization by Candida spp. and MRSA. The objective of this study was to investigate the antifungal activity of amlodipine against Candida spp. strains in planktonic and biofilm forms, to elucidate its possible mechanism of action, and to evaluate its effect on mixed biofilms of Candida spp. and MRSA, both in 96-well polystyrene plates and in Peripheral Venous Cathe-ters (PVCs). To this, an Antifungal Susceptibility Test was performed to determine the Mi-nimum Inhibitory Concentrations (MICs). The action of amlodipine against Candida spp. and Candida spp. plus MRSA biofilms was determined by the MTT assay, and its possible me-chanism of action was investigated through flow cytometry tests. The results demonstrated that amlodipine exhibited Minimum Inhibitory Concentrations (MICs) ranging from 62.5 to 250μg/mL, as well as significant action on mature and pre-formed and forming biofilms, promoting reductions between 50% and 90%. Additionally, the drug increased phosphatidyl-serine externalization and reduced fungal cell viability, suggesting induction of apoptosis. It was also observed that amlodipine reduced metabolic viability by approximately 90% in “in vitro’ polymicrobial biofilms at a concentration equivalent to 8xMIC (1000-2000 μg/mL), in all combinations tested, as well as exerting a potent action on mixed biofilms in CVPs, with a reduction in the number of colonies between 60% and 90%. Furthermore, the morphology was evaluated by light microscopy, confirmed by Scanning Electron Microscopy (SEM). Ba-sed on these findings, amlodipine emerges as a potential candidate for the treatment of fungal and mixed infections. However, additional in vivo studies are needed to validate and expand these results Tipo: Tese