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Infecção por Escherichia coli não diarreiogênica altera os aspectos morfofuncionais em modelo murino de desnutrição

Thu, 01 Jan 2026 00:00:00 GMT

Título: Infecção por Escherichia coli não diarreiogênica altera os aspectos morfofuncionais em modelo murino de desnutrição Autor(es): Alves, Ana Elisa da Silva Abstract: Childhood malnutrition remains a major challenge in low- and middle-income countries, compromising growth, immunity, and the intestinal barrier. Although diarrheagenic *E. coli* pathotypes have been extensively studied in this context, the intestinal effects of uropathogenic strains (UPEC) remain poorly explored. This study investigated, in a murine model, the effects of UPEC infection combined with the MAL-ED multi-deficient diet on intestinal epithelial structure and function, correlating the findings with the strain's whole- genome sequencing. C57BL/6 mice were assigned to six experimental groups and monitored for 21 days, with assessments of clinical parameters, body composition, intestinal function (lactulose/mannitol test), and small intestine morphometry. UPEC infection significantly reduced growth, fat-free mass, and body water compartments, with more pronounced effects in malnourished animals (p<0.05). Alterations in villus and crypt areas and increased intestinal permeability were observed in infected animals, particularly those on the multi- deficient diet (p=0.0023). Genomic analysis revealed virulence genes and toxins associated with intestinal barrier damage. The combination of malnutrition and UPEC infection exacerbated the impairment of epithelial integrity and growth, demonstrating that extra- intestinal strains can negatively modulate intestinal pathophysiology and highlighting the model's potential to inform nutritional and therapeutic interventions for vulnerable pediatric populations Tipo: Dissertação

Atividade antifúngica in vitro da doxepina em células planctônicas e biofilme de Candida spp.: determinação do possível mecanismo de ação e expressão gênica

Thu, 01 Jan 2026 00:00:00 GMT

Título: Atividade antifúngica in vitro da doxepina em células planctônicas e biofilme de Candida spp.: determinação do possível mecanismo de ação e expressão gênica Autor(es): Pinheiro, Dávylla Rênnia Saldanha Abstract: Invasive fungal infections represent a significant public health issue due to high mortality rates, particularly those caused by Candida spp., the leading cause of bloodstream infections in healthcare settings. Rising antifungal resistance has spurred the search for novel therapeutic strategies, including drug repurposing and synergistic combinations with existing antifungals. In this context, this study aimed to investigate the in vitro antifungal activity of the tricyclic antidepressant doxepin (DOX) against fluconazole-resistant Candida spp. strains, evaluating both planktonic and biofilm forms. DOX's inhibitory effect was assessed via broth microdilution to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), alongside checkerboard assays to evaluate drug interactions with antifungals and the drug's impact on biofilms. These tests were followed by flow cytometry and in vitro cytotoxicity assessments using human cells. Molecular analyses included docking studies and gene expression analysis via qRT-PCR. DOX demonstrated fungicidal activity against all strains—with MIC50 values ranging from 64 to 256 μg/mL— and significantly reduced biofilm formation. When combined with amphotericin B, a synergistic effect predominated, resulting in increased efficacy at lower concentrations compared to the drugs used alone. Mechanistically, DOX induced oxidative stress, mitochondrial dysfunction, and apoptosis, thereby reducing fungal viability. In silico ADME profiling indicated high lipophilicity, favoring the molecule's interaction with polymeric surfaces such as catheters, while assays using human cells demonstrated low cytotoxicity. Furthermore, interactions with Als3 and Sap5 proteins were observed, alongside alterations in the expression of virulence-related genes, such as ALS3, SAP5, ECE1, and HWP1. These findings indicate that DOX exhibits promising antifungal activity in the treatment of Candida infections, highlighting its potential against biofilms Tipo: Dissertação

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

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