http://repositorio.ufc.br/handle/riufc/194 2026-06-11T19:41:59Z http://repositorio.ufc.br/handle/riufc/85403 Título: Doença valvar cardíaca em pacientes com morbidades metabólicas: uma análise histopatológica e metagenômica. Estudo de série de casos Autor(es): Pinho Filho, João Eudes Teixeira Abstract: Heart disease has been the leading cause of death worldwide. Among these conditions, calcification of heart valves stands out, occurring due to a degenerative process influenced by infections associated with an inflammatory state. In this context, the objective of this study was to identify the microorganisms present in heart valves removed from cardiac patients through metagenomic analysis. This is an observational, cross-sectional, case-control study of samples collected from heart valves of patients undergoing valve replacement surgery. 27 valve leaflets from patients with valvular heart disease and 9 from the control group were histologically analyzed for the presence of inflammation and mineralizations. Giemsa and Grocott histochemical analyses were performed to evaluate possible bacteria and fungi present in the sample. The DNAs from the heart valve samples were extracted and frozen for PCR analysis. Furthermore, metagenomic sequencing of the 16S and 18S rRNA regions was performed, followed by bioinformatic analysis. The results demonstrated an unfavorable cardiometabolic profile, with hyperglycemia and reduced HDL cholesterol. Histologically, diffuse fibrosis, chronic inflammation, myxoid degeneration, and calcification predominated. Histochemical analysis with Groccot and Giemsa staining identified a significant frequency of structures compatible with microorganisms, especially bacteria and fungi. Metagenomic analysis identified potentially opportunistic bacteria and fungi, including Staphylococcus, Sphingomonas, Actinotignum, Cutaneotrichosporon, and Apiotrichum. It is concluded that the valvular heart diseases analyzed present a multifactorial character, involving interactions between metabolic, inflammatory, degenerative, and microbiological alterations, highlighting the relevance of metagenomics as a complementary tool in the investigation of valvular heart diseases. Tipo: Tese 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/84872 Título: Avaliação dos efeitos de p-cimeno em câncer: revisão de escopo e estudo In vitro Autor(es): Viana, Khalil Fernandes Abstract: Conventional oncological therapies tend to mutilate patients and generate pharmacological resistance and adverse effects. The use of natural compounds stands out as an alternative in this therapy, as it minimizes the deleterious effects and enhances the action of chemotherapeutics, acting as an adjuvant. P-cymene (pC), a monoterpene present in several plants, has already been evaluated in preclinical cancer studies, showing preventive and therapeutic effects. However, these findings need to be better mapped and analyzed in order to elucidate the best strategies for using this compound in cancer therapy. This thesis aimed to review and map the published findings on the actions of pC in cancer, as well as to evaluate the in vitro activity of this compound in two oral cancer cell lines. For this, a scoping review was performed using PRISMA-ScR as a guide and using the bibliographic databases Embase, Scopus, Pubmed and Web of Science for the selection of studies. The laboratory study was based on cell cultures of the following cell lines: UM-HACC-2A (salivary adenoid cystic carcinoma), in which cell viability assays (Live/Dead assay method) were performed to obtain the IC50 of pC, immunofluorescence of NFκB and Ki-67, cell migration and analysis of the nuclear area; SCC-4 (oral squamous cell carcinoma), in which cell viability assays (MTT method), gene expression of Caspases 3 and 9, Bcl-2 and Akt, immunocytochemistry of PI3K, Ki-67 and Akt proteins, as well as cell migration were performed; and HaCat (normal keratinocytes), as control. The Shapiro-Wilk test, t-test, Mann-Whitney test and nonlinear regression were the statistical methods applied, with a significance level of 5% (p<0.05) adopted for all analyses. The results of the scoping review revealed that 93.7% of the included in vitro studies showed pC IC50 values considered to be of low cytotoxic potential by the National Cancer Institute (NCI), with a mean value of 178.43 μg/ml, being tested in colorectal, breast, lung, liver, cervical, skin, fibrosarcoma and melanoma cancers and acting mainly through non-cytotoxic mechanisms, such as alteration of cell signaling pathways (inhibition of ERK1/2 and p38 MAPK and activation of TIMP-1), modulation of the tumor microenvironment (reduction of SOD, increase of IL-6 and reduction of IL-1) and inhibition of invasion (reduction of MMP-9), and secondarily through cytotoxic mechanisms, such as DNA damage (increase of 8-OHdG) and plasma membrane (increase of malondialdehyde), and increase of Caspase-3 activity. Animal studies have shown significant results in reducing the incidence of tumors in colorectal cancer and tumor size in colorectal cancer and melanoma. The results of the in vitro study demonstrated low cytotoxicity of pC in UM-HACC-2A (IC50=664.7 μg/ml), in SCC-4 (IC50=573.6μg/ml) and in normal keratinocytes (IC50=694,6 μg/ml), with a selectivity index (SI) of 1.12. In the UM-HACC-2A cell line, significant inhibition of the expression of NFκB (p=0.026) and Ki-67 (p=0.005) proteins was observed, as well as a reduction in nuclear area (p<0.0001), but there was no statistically significant difference in the migration of UM-HACC-2A cells. In SSC-4 cells, there was inhibition of cell migration (p=0.0005), reduction in the expression of PI3K, Ki-67 and Akt proteins (p=0.0286); however, no significant changes were observed in the gene expression of Caspase 3 and 9, Bcl-2 and Akt. It is concluded that, although pC presents low direct cytotoxicity against tumor cells, its effects on cell signaling pathways, tumor microenvironment, cell invasion and migration processes, as well as chemoprevention in animal models, suggest its use as an adjuvant agent in oncological therapy, acting as a modulator of tumor progression and potentially increasing the efficacy of conventional cytotoxic therapies. Continued studies, with emphasis on in vivo models and proteomic analyses, are essential to deepen the knowledge about its mechanisms of action and therapeutic potential. Tipo: Tese 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/84398 Título: Dimorfismo sexual em exames de imagem de estruturas neurocranianas: revisões sistemáticas, análise morfológica e morfométrica tridimensional da sela túrcica e forame magno e predição do sexo por aprendizado de máquina Autor(es): Ribeiro, Esther Carneiro Abstract: Sexual dimorphism in neurocranial structures plays a relevant role in estimating biological sex and is of great interest in forensic anthropology and human identification. This study aimed to evaluate sexual dimorphism based on linear, volumetric, and morphological parameters of the sella turcica (ST) and foramen magnum (FM) in multislice computed tomography (MSCT) scans, integrating systematic reviews, three-dimensional analyses, and machine learning algorithms. Initially, two systematic reviews were conducted and registered in the PROSPERO database. These reviews synthesized evidence on sexual dimorphism in neurocranial structures and on the role of the ST in sex estimation among non-syndromic individuals. Searches across multiple databases resulted in meta-analyses of linear and volumetric measurements. The findings revealed significantly smaller neurocranial dimensions in females, with high reliability for measurements obtained through tomography. For the ST, length and diameter differed between sexes, although the certainty of the evidence was rated very low, highlighting the need for further studies with greater methodological standardization. In the analytical phase, 200 MSCT scans from adult individuals from northern and northeastern Brazil were examined to assess ST morphology according to the classifications proposed by Axelsson and Yasa. The normal, oblique anterior, round, and flat shapes were associated with sex among individuals under 30 years old, underscoring the potential of ST morphology as a complementary marker of sexual dimorphism. Subsequently, three-dimensional measurements of the ST and FM were obtained from 228 adult scans using semi-automatic segmentation and standardized cranial orientation with ITK-SNAP and 3D Slicer software. Intra-examiner reproducibility was high (ICC 0.81–0.98). All FM dimensions and most ST measurements were smaller in females, with statistically significant differences. Discriminant formulas yielded an area under the curve (AUC) of 0.798 (95% CI: 0.740–0.855), and machine learning algorithms—particularly the Support Vector Machine (SVM)—achieved moderate performance, with AUC values up to 0.8351 (± 0.0888) when both structures were evaluated together. The findings confirmed the sexual dimorphism of the ST and FM, reinforcing their value as useful anatomical markers for sex estimation. The integration of three-dimensional analyses and machine learning models demonstrated potential to enhance the accuracy of sex classification and broaden the applicability of imaging techniques in forensic anthropology. Although the results are promising, consolidation of these approaches requires external validation across diverse populations and standardization of acquisition and segmentation protocols. Tipo: Tese 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/83877 Título: Influência do perfil inflamatório celular no microambiente tumoral no prognóstico e meta-análise da sensibilidade imunohistoquímica na detecção de invasão perineural e angiolinfática em carcinoma de células escamosas oral Autor(es): Paula, Dayrine Silveira de Abstract: The prognosis of oral squamous cell carcinoma (OSCC) is related to staging and the tumor microenvironment (TMA), which is highly heterogeneous, complex, and composed of different cell types. This work has two chapters, comprising a systematic review with meta-analysis and a retrospective study. The aim is to understand the influence of the cellular profile of the tumor microenvironment on the prognosis of OSCC. In Chapter 1, a systematic review and meta-analysis (PROSPERO - CRD 42021256515) was performed to analyze whether immunohistochemistry is more sensitive than hematoxylin-eosin staining for identifying perineural or angiolymphatic invasion in OSCC. Data were obtained from six databases (PubMed, Scopus, LILACS, Web of Science, EBSCO, LIVIVO, Embase) and grey literature. The meta-analysis (random effect) was calculated using MedCalc 18.2.1 software (MedCalc®) (p<0.05). Four observational studies were included, totaling 560 patients with 295 biopsies reviewed for pathologies and analyzed by immunohistochemistry. The combined sensitivity was 76%, since the samples evaluated by Hematoxylin-Eosin (HE), which detected perineural invasion (PNI) and lymphovascular invasion (LVI), were also identified by the immunohistochemical method. The specificity of the four included studies revealed that, using HE, 42% of squamous cell carcinomas (SCCCs) did not show PNI and LVI, which was confirmed by performing the immunohistochemical technique. Therefore, the use of immunohistochemical reactions to highlight tumor invasion in nerves and blood or lymphatic vessels is effective in cases where H&E analysis resulted in a negative result, thus decreasing the prevalence of false negative cases. Chapter 2 aimed to characterize the immunoexpression of macrophage and lymphocytic phenotypes in oral squamous cell carcinoma, correlating it with prognostic factors and cell proliferation markers. To this end, 228 oral squamous cell carcinoma (OSCC) samples from the Ceará Cancer Institute (ICC) were evaluated. Sociodemographic and clinicopathological data were collected, and immunohistochemistry was performed for anti-CD3, CD4, CD8, CD20, and CD68 markers in peritumoral and intratumoral regions. However, Ki67 was only found in the intratumoral area. The percentage of immunostaining was calculated and associated with other variables using the Friedman/Dunn and Wilcoxon tests. The most frequent lymphocyte profile was CD3 positive in the peritumoral region (p<0.001). Furthermore, Ki-67 expression >5% was associated with high intratumoral CD4 expression (p=0.018). It was observed that patients with lymphovascular invasion presented high expression of peritumoral CD8 (p=0.034) and CD20 (p=0.034). Tumor sprouting was significantly related to low expression of CD68 in the peritumoral region (p=0.035). Multivariate analysis demonstrated that peritumoral CD20 is inversely related to recurrence-free survival at 18 months, reducing the risk of recurrence at 18 months by 0.291 times, while intratumoral CD68 is directly related, increasing the risk of recurrence at 18 months by 5.07 times. Furthermore, lymphovascular invasion (p=0.001) and nodal metastasis (p=0.009) significantly increased the risk of recurrence at 18 months in patients with oral squamous cell carcinoma. The participation of BCD20+ lymphocytes in the tumor microenvironment may provide antitumor behavior, since the loss of expression of these cells led to an increased risk of recurrence of oral squamous cell carcinoma. Furthermore, increased CD68+ expression was shown to increase the risk of oral cancer recurrence. Therefore, lymphovascular invasion and nodal metastasis proved to be independent predictors of recurrence. Tipo: Tese 2025-01-01T00:00:00Z