DSpace Coleção: PPGBCM

Avaliação da expressão do gene TP53 em amostras de pacientes com câncer colorretal e sua correlação com fatores prognósticos

2023-03-31T00:00:00Z

Título: Avaliação da expressão do gene TP53 em amostras de pacientes com câncer colorretal e sua correlação com fatores prognósticos Autor(es): Tomaz, Alécia Coura Orientador: Martina, Glaucia Verissimo Faheina Abstract: Colorectal cancer (CRC) is a neoplasm that affects the large intestine in its segments of the colon, rectum and anus. It is the third most commonly diagnosed cancer and the second leading cause of cancer-related death worldwide. Some of the risk factors for colorectal cancer include: high fat diet, sedentary lifestyle, obesity, smoking and excessive alcohol consumption. Among the genes that are frequently mutated, alterations in the TP53 gene are considered one of the main genetic alterations related to the development of CRC. Sociodemographic factors such as ethnicity and socioeconomic status are known to influence the incidence, stage, diagnosis, survival and mortality of this cancer. The aim of this study was to carry out an ambispective cohort study of patients with Colorectal Cancer using paraffin-blocked samples. As well as analyzing TP53 gene expression by real-time PCR in fresh samples from patients at Hospital Napoleão Laureano in João Pessoa/PB, Brazil. Statistical analyzes were performed using SPSS® software, version 22.0 and the public domain program OpenEpi, version 3.01. Association tests were performed, such as Pearson's Chi-square and Fisher's Exact Test, the P value considered statistically significant <0.05. Positive p53 staining was observed in 46.5% of the 43 patient samples analyzed by immunohistochemistry, and 53.5% were negative. Of the samples analyzed for immunohistochemistry, it was found that 55.8% of the patients were female, with a mean age above 60 years (79.1%). The most frequent ethnicity was brown people (81.4%). Regarding the laterality of the tumor, the region of the left colon was more frequent (60.4%), and the most present histological grade was the moderately differentiated (88.3%). As for the morphological pattern, the tubular was the most frequent (74.4%). With regard to Internship, II was the most observed in the study population (81.4%). Metastasis in lymph nodes was absent in most of the individuals analyzed (51.1%). Patients who presented positive marking for carcinoembryonic antigen (CEA) corresponded to 30.2%, considered positive when CEA > 4.0 ng/ml. There was no significant association between p53 expression and any of the analyzed variables (gender, age, education, ethnicity, location, histological grade, histological pattern, stage and positive quantification for CEA). In the analyzes of TP53 gene expression by real-time PCR, performed in fresh samples (n=10), a higher expression of TP53 was observed in normal tissues (adjacent to the tumor) in relation to tumor tissue (p< 0.05 ). The analysis of data from this cohort allowed us to better understand the profile of the disease, highlighting the main sociodemographic and clinical factors associated with the disease, making it possible to assist in possible preventive and management practices for the patient. However, it was not possible to associate p53 expression with other markers such as CEA, or with other pathological clinical factors. More comprehensive studies with a larger number of patients may possibly better clarify the contribution of p53 as a biomarker for colorectal cancer. Editor: Universidade Federal da Paraíba Tipo: Dissertação

Avaliação dos efeitos tóxicos da peçonha de Bothrops jararacussu sobre embriões e larvas de peixe-zebra (Danio rerio)

2022-02-25T00:00:00Z

Título: Avaliação dos efeitos tóxicos da peçonha de Bothrops jararacussu sobre embriões e larvas de peixe-zebra (Danio rerio) Autor(es): Silva, Layssa Gualberto da Orientador: Salvador, Daniela Priscila Marchi Abstract: Ophidism is a neglected disease responsible for affecting approximately 2.7 million people worldwide, mainly affecting tropical and subtropical countries. In Brazil, 90% of the reported and identified cases of these accidents are caused by snakes of the Bothrops genus. Bothrops jararacussu has clinical relevance, and its venom is composed of substances capable of triggering local and systemic effects, culminating in the development of morbidities and/or mortality in the affected individual. The present study aimed to evaluate the toxic effects triggered by the presence of the venom on the zebrafish embryo and larvae model system. The stability of B. jararacussu venom under the conditions used in the toxicity experiments in zebrafish embryos and larvae was evaluated by measuring the prothrombin and activated partial thromboplastin times of citrated human plasma in the presence of different amounts of the venom and in different exposure times. In addition, the mortality rate, morphological alterations, spontaneous movements and heart beats of embryos were evaluated, as well as certain parameters of toxicity and alterations in the biochemical profile of the biomarker enzymes of toxicity (glutathione-S-transferase, catalase, lactate dehydrogenase, and acetylcholinesterase) of zebrafish larvae after exposure to B. jararacussu venom. Acute toxicity was assessed by semi-static exposure of zebrafish embryos and larvae to the venom for 96 hours. Our results indicated that B. jararacussu venom causes toxicity in zebrafish embryos and larvae, causing embryo mortality in the first 24 hours of exposure, in addition to altering the number of spontaneous tail movements and acetylcholinesterase activity. Changes in the activities of the other antioxidant enzymes evaluated were also verified. The evaluation of these results allows us to suggest that the toxic effects caused by the presence of the venom in the early stages of zebrafish development are mediated, by neurotoxic action, induction of oxidative and metabolic stress possibly caused by low molecular weight components and/or proteins that makes up the venom. Toxinological evaluations using zebrafish as a model are scarce, however, this study presented promising results that encouraged the development of future research in snake toxinology using this animal as a model organism. Editor: Universidade Federal da Paraíba Tipo: Dissertação

Avaliação dos efeitos terapêuticos de Lactococcus lactis carreadora do vetor de expressão eucariótica que codifica para scFv anti-TNFa em modelo de colite induzida por TNBS

2020-02-28T00:00:00Z

Título: Avaliação dos efeitos terapêuticos de Lactococcus lactis carreadora do vetor de expressão eucariótica que codifica para scFv anti-TNFa em modelo de colite induzida por TNBS Autor(es): Viana, Giovana Cristina Santana Orientador: Almeida, Juliana Franco Abstract: Crohn’s disease (CD) belongs to the group of infectious intestinal diseases (IBD), and is characterized by an intestinal infection caused by severe infections of the mucosa, which cannot be cured by clinical or surgical treatment and which can affect the entire gastrointestinal tract. TNF-α plays a fundamental role in the disease, being considered the best therapeutic target. However, an intravenous route of immunotherapies causes immunogenicity and systemic effects. To circumvent these restrictions, local delivery of these drugs could benefit patients, restrict therapy to the inflammatory site. The development of Lactococcus lactis cephas is capable of providing a eukaryotic expression vector that encodes a single chain variable fragment (scFv) of antibody represents a new strategy for the analysis of a more effective alternative therapy for isolated expression in the intestine, against CD. In this way, the objective of this work was to evaluate the therapeutic effects of fragments of scFv use anti-TNF-α used locally in the intestinal mucosa using L. lactis as a vehicle for delivery of vectors in the intestinal mucosa, in the experimental Crohn's disease model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Thus, the effect of producing these filters directly on the intestinal mucosa was analyzed. Female BALB c mice were used, with experimental colitis induction by TNBS for four weeks. The L. lactis culture was administered orally in the last 5 days of the protocol. No day after the last day of treatment, the animals were sacrificed and with different temperature variations. He observed an improvement in the group treated with L. lactis FnBPA + (pValac :: anti-TNFα) in the macroscopic parameters of the disease in relation to the unused groups. In the histological analysis, the beneficial effect of the treatment was better observed in the proximal region, with reduction of the inflammatory infiltrate and maintenance of the mucous layer. With these results, we conclude the treatment with pValac :: anti-TNFα has a mitigating effect on the experimental collection model, and the most recent studies are adequate to elucidate the molecular mechanisms used by the effect and, thus demonstrating a strategy based on in delivering DNA. Editor: Universidade Federal da Paraíba Tipo: Dissertação

Diagnóstico via análise sonora da condição de funcionamento e nível de severidade em um redutor coroa sem-fim utilizando redes neurais artificiais

2024-12-18T00:00:00Z

Título: Diagnóstico via análise sonora da condição de funcionamento e nível de severidade em um redutor coroa sem-fim utilizando redes neurais artificiais Autor(es): Pires, Raul Bernardo de Pontes Orientador: Rodrigues, Marcelo Cavalcanti Abstract: This work developed an intelligent diagnostic system for identifying the operational conditions of a worm gear reducer. An experimental setup was built to reproduce different operating conditions and severity levels, starting from the reference state (good condition). Among the tested conditions are angular misalignment, overload, and inefficient lubricat ion. The setup incorporated a data acquisition system for vibration analysis, primarily using an Arduino and an MPU 6050 accelerometer, as well as sound analysis via a smartphone. The vibration data were used to validate the system's dynamics and perform a comparative analysis with the sound signals through Fast Fourier Transform (FFT). For the sound signals, analyses were performed in the time domain using statistical techniques such as Kurtosis, Crest Factor, and RMS; in the frequency domain using the Fas t Fourier Transform (FFT); and in the time frequency domain using the Wavelet Transform. An intelligent diagnostic system was developed, consisting of two neural networks: one responsible for classifying the operational condition (reference state, angular misalignment, overload, and inefficient lubrication) and another for identifying severity levels (mild, medium, and severe). The accuracy achieved for operational condition classification was 98.889%, and for severity classification, it was 98.045%. In cro ss validation, the average accuracy obtained was 97.738% for the operational condition neural network and 97.403% for the severity level neural network. Based on the results, it was found that sound signals, in conjunction with the neural network, were eff ective in determining the operational conditions. Editor: Universidade Federal da Paraíba Tipo: Dissertação