DSpace Coleção:

Avaliação da expressão dos genes do ritmo circadiano como potenciais biomarcadores em pacientes portadores de leucemia mielóide aguda

2026-05-05T19:14:48Z

Título: Avaliação da expressão dos genes do ritmo circadiano como potenciais biomarcadores em pacientes portadores de leucemia mielóide aguda Autor(es): Cunha, Leidivan Sousa da Abstract: Acute myeloid leukemia (LMA) is an aggressive hematological malignancy, common in adults, characterized by high mortality and marked genetic heterogeneity. Growing evidence indicates that dysregulation of the circadian rhythm (RC) and its core genes, the Clock Genes (CG), CLOCK, BMAL1, NPAS2, and the negative regulator CIPC, interferes with key oncogenic processes, including cell proliferation, DNA repair, and energy metabolism. In this context, this study aims to evaluate the expression of CG as potential biomarkers in adults with LMA in the state of Ceará. This is a prospective, observational, and analytical study including 90 patients with LMA (mean age 56.6 years; predominantly male) treated at referral centers in Ceará, and 40 healthy controls. Paired peripheral blood (SP) and bone marrow (MO) samples were collected for RNA extraction, cDNA synthesis, and gene expression quantification by RT-qPCR. Diagnostic performance was assessed using ROC curves, logistic regression models, and a Random Forest algorithm. No significant differences were observed in CG expression between SP and MO, supporting the use of SP as a surrogate tissue. Patients with LMA showed a marked reduction in the expression of NPAS2, BMAL1, CLOCK, and CIPC compared to controls (p<0.001). Among individual markers, NPAS2 demonstrated the best discriminative performance (AUC 0.925; 95% CI: 0.87–0.98), explaining 65.1% of the outcome variability in the logistic model. The combined four-gene model achieved an AUC of 0.946, with no statistically significant improvement over the model with NPAS2 alone (p=0.183). The Random Forest model showed 74% sensitivity and 100% specificity, highlighting NPAS2 as the most important predictive variable. Thus, LMA is associated with a marked dysregulation of CG expression. NPAS2 stands out as a robust diagnostic biomarker, with high discriminative performance and potential clinical applicability. These findings expand the understanding of leukemogenesis from a circadian perspective and support the exploration of biological clock pathways as diagnostic and therapeutic targets. Tipo: Dissertação

Biomarcadores de doenças em remanescentes ósseos e dentes dos sítios arqueológicos Moconha (Serra Grande) e Chã das Laranjeiras (Pilõezinhos), estado da Paraíba, Brasil

2026-04-10T17:31:20Z

Título: Biomarcadores de doenças em remanescentes ósseos e dentes dos sítios arqueológicos Moconha (Serra Grande) e Chã das Laranjeiras (Pilõezinhos), estado da Paraíba, Brasil Autor(es): Cavalcante, Thamires Silva Abstract: Disease Biomarkers in Bone and Dental Remains from the Archaeological Sites of Moconha (Serra Grande) and Chã das Laranjeiras (Pilõezinhos), State of Paraíba, Brazil. Thamires Silva Cavalcante.Advisor: Juvandi de Souza Santos. Co-advisor: Allysson Allan Farias. Master's Dissertation. Graduate Program in Translational Medicine. Research and Drug Development Center, School of Medicine, UFC. Fortaleza, 2026. The present research aimed to identify disease biomarkers, biological characteristics associated with morphological alterations observed in human teeth and bones, in order to establish a preliminary profile of dental and skeletal conditions in past individuals. The analyzed samples consist of human bones and teeth recovered from secondary burials placed in funerary urns associated with the Tupiguarani and Aratu ceramic traditions, collected from the archaeological sites of Moconha (Serra Grande, Paraíba, Brazil) and Chã das Laranjeiras (Pilõezinhos, Paraíba, Brazil). At the first site (SAM–SG), 34 bone samples and 8 human teeth were recorded, while at the second site 29 bone samples and 15 human teeth were identified. The research methodology followed interdisciplinary laboratory principles grounded in approaches from Translational Medicine, Translational Bioarchaeology, Forensic Anthropology, Radiology, Dentistry, and Histopathology. Preliminary results identified acidic pH levels below 7 in the sediment found within the urns at both sites, which represents one of several factors associated with the deterioration of human bones and teeth. Among the health-related biomarkers identified, a consolidated fracture was observed in a partially preserved humerus, presenting bone callus formation and bone remodeling, indicating that the individual survived the injury. Radiographic and microtomographic analyses enabled the evaluation of structural inconsistencies in the trabecular field and cortical density associated with pathological and mechanical processes. Furthermore, the Minimum Number of Individuals (MNI) analysis identified remains corresponding to at least three biologically male individuals at the SAM–SG site and one individual at the Chã das Laranjeiras site (SAL–PL). Dental analyses revealed enamel hypoplasia, severe wear, dental calculus, and carious lesions, conditions associated with physiological stress and abrasive dietary patterns. Finally, a fragment of a human mandible from the SAM–SG site was subjected to histopathological examination. This study enabled the establishment of a preliminary profile of these past populations through the investigation of biomarkers preserved in human bones and teeth, providing new historiographical, archaeological, and bioarchaeological perspectives on the life and health conditions of part of the ancient Indigenous populations of Northeastern Brazil. Tipo: Dissertação

Efeitos da laminarina sobre domínios afetivos e cognitivos em camundongos submetidos a estresse repetido imprevisível

2026-04-03T11:55:30Z

Título: Efeitos da laminarina sobre domínios afetivos e cognitivos em camundongos submetidos a estresse repetido imprevisível Autor(es): Batista, Pauliane Valeska Chagas Abstract: Major Depressive Disorder (MDD) is a common neuropsychiatric condition that affects a substantial proportion of people worldwide, many of whom do not respond a satisfactory therapeutic response with current drug treatments. Given the therapeutic limitations of current antidepressants for the MDD, laminarin (LAM) emerges as an important beta-glucan with immunomodulatory potential, which interacts with the Dectin-1 receptor, a pattern recognition receptor (PRR) found in immune system cells. In the neuropsychiatric field, this beta-glucan has been investigated in preclinical studies as a therapeutic strategy for depression due to its applicability in modulating the neuroimmune axis. In this regard, the purpose of this study was to evaluate the behavioral and neurochemical effects of LAM administered to BALB/c mice in an animal model of depression induced by repeated unpredictable stress (ERI). To this end, male BALB/c mice were subjected to a stress-inducing protocol for a period of 21 days. Subsequently, they were treated with saline (SAL, intraperitoneally), desvenlafaxine (DSV, 10 mg/kg orally), or laminarin (LAM, 20 mg/kg intraperitoneally). Behavioral analysis included the open field test (OFT), tail suspension test (TST), splash test, Y-maze, and object recognition test (ORT). The findings revealed that the stress model used was unable to induce a consistent depressive-like phenotype, as evidenced by the TSC and splash test, nor did it affect the animals’ memory, body weight, or locomotor activity. Similarly, LAM did not alter locomotor and exploratory activity in the OFT, nor did it demonstrate an antidepressant effect in the TSC. In contrast, LAM reversed the effects of ERI on the parameters of grooming time and frequency in the splash test, suggesting a possible pro-motivational effect on the animals’ self-care behavior. Regarding for memory, LAM did not improve or impair recognition ability in the TRO, possibly due to the absence of a prior deficit in the model used. In the Y-Maze test, no changes in short-term memory induced by LAM were observed. Furthermore, LAM did not alter the animals’ weight variation. With regard to oxidative stress, LAM did not exhibit a neuroprotective profile under the conditions used, reducing GSH levels in the HC and contributing to increased lipid peroxidation in the CE. Tipo: Dissertação

Efeito antiinflamatório e antioxidante do honokiol na prole de ratos wistar induzida ao autismo expostos ao ácido valpróico no período pré-natal

2026-02-24T18:11:26Z

Título: Efeito antiinflamatório e antioxidante do honokiol na prole de ratos wistar induzida ao autismo expostos ao ácido valpróico no período pré-natal Autor(es): Santos, Camila Nogueira dos Abstract: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a high global prevalence, manifested through behavioral characteristics, as well as restricted and repetitive patterns of behavior and atypical sensory responses. Honokiol, a polyphenolic bioactive substance considered one of the main components extracted from the plant Magnolia officinalis, possesses several therapeutic properties involving antioxidant, anti-inflammatory, antimicrobial, anticancer, antithrombotic, antidepressant, and neuroprotective actions. This study investigates its effects on behavior, oxidative stress, proteins, AChE, monoamines, and intestinal disaccharidases in an animal model of ASD. Initially, in silico analyses were performed to predict pharmacokinetics, toxicity, identification of pharmacological targets, and the strength of interaction and conservation of protein structure between rats and humans. In the in vivo study, eight-week-old nulliparous male and female Wistar rats were used as breeding stock (CEUA/UFC: 89011223-0). The female breeding stock were randomly divided into four groups according to the treatment they received: control, VPA (valproic acid 600 mg/single dose), honokiol (honokiol 10 mg/kg/day), VPA+honokiol (valproic acid + honokiol, at the same doses as above). The pups (females and males) were used for behavioral, neurochemical, and digestive evaluation. Behavioral activity was assessed using open field tests, social interaction tests, elevated plus maze, and Y-maze tests. In the locomotor evaluation, considering spontaneous movement parameters, females in the VPA+HK group showed an approximately 45.4% reduction in the number of matings compared to the VPA group. Regarding anxious behavior, it was observed that females in the VPA group presented less anxiety and greater impulsivity; however, treatment with honokiol reduced this impulsivity by 57.6% in the VPA+HK group when compared to the VPA group. In the oxidative profile, honokiol promoted significant antioxidant effects: it reduced MDA levels in the prefrontal cortex by 40.7% and in the hippocampus by 42% compared to the VPA group. Furthermore, it increased GSH levels in the hippocampus by 94%, although it reduced this concentration in the prefrontal cortex by 80% compared to the control group. A decrease in total proteins was also observed in the prefrontal cortex of males by 20.5%, and in females there was a 16.4% reduction in the hippocampus in the VPA+HK group compared to the VPA group. In the monoaminergic system, honokiol reduced serotonin levels by 58% in males and 44.6% in females (VPA versus VPA+HK). In the cholinergic system, a 38% reduction in acetylcholinesterase (AChE) levels was observed in the hippocampus of females treated with honokiol. Finally, in the intestine, honokiol increased sucrase enzyme activity by 1.68 times in males compared to the VPA group. Taken together, these results demonstrate that honokiol exerted a significant neuroprotective action in the VPAinduced ASD model, by increasing glutathione levels, reducing MDA and total proteins, improving risk perception, and modulating serotonergic and cholinergic pathways, favoring greater serotonin availability and lower AChE activity. Tipo: Dissertação