https://repositorio.ufba.br/handle/ri/11280 Mon, 04 May 2026 06:49:33 GMT 2026-05-04T06:49:33Z https://repositorio.ufba.br/handle/ri/44161 Título: Marcadores histológicos de cronicidade e progressão na glomeruloesclerose segmentar e focal Autor(es): Silva, José Nathan Andrade Muller da Primeiro Orientador: Santos, Washington Luís Conrado dos Abstract: Segmental and focal glomerulosclerosis not otherwise specified (FSGS NOS) is a glomerulopathy with undefined outcome. We reviewed possible histopathological markers of chronicity from the literature and identified 33 cases of FSGS NOS for our sample. Based on the frequency of certain markers, we developed an experimental scoring system that uses tubular atrophy, interstitial fibrosis, glomerular hyalinosis, arteriolosclerosis, and glomerular sclerosis. We applied an experimental scoring system to predict chronicity. Our analysis revealed a sensitivity of 0.66 and a specificity of 0.80. Glomerular hyalinosis emerged as the most reliable isolated parameter, with a sensitivity of 0.83 and a specificity of 0.70. We obtained a survey of risk mutation of APOL1 genes from 25 of 33 patients. Additionally, we conducted our specimen in scanning for future endeavors in digital pathology for AI training. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Dissertação Fri, 24 Jan 2025 00:00:00 GMT https://repositorio.ufba.br/handle/ri/44161 2025-01-24T00:00:00Z https://repositorio.ufba.br/handle/ri/43888 Título: Avaliação do papel do gene lpg2 durante infecção de macrófagos por Leishmania amazonensis Autor(es): Goicochea, Astrid Madeleine Calero Primeiro Orientador: Borges, Valéria de Matos Abstract: INTRODUCTION: Leishmaniasis is a disease caused by protozoa of the genus Leishmania, belonging to the Trypanosomatidae family, and remains a significant public health problem in several regions of the world, including Brazil. Leishmania amazonensis is the main species associated with diffuse cutaneous leishmaniasis (DCL), although it is also involved in cases of localized cutaneous leishmaniasis (LCL). Our group has been investigating inflammatory mechanisms triggered by surface glycoconjugates of promastigotes, such as lipophosphoglycan (LPG) and other phosphoglycans (PPGs). Strategies based on parasites deficient in these molecules have been fundamental to understanding their role during infection. OBJECTIVES: This study aimed to investigate the contribution of the lpg2 gene to the early stages of the host-parasite interaction and the survival of L. amazonensis in murine macrophages. METHODS: Bone marrow-derived macrophages from C57BL/6 mice were infected with wild-type (WT) or lpg2-deficient (Δlpg2) L. amazonensis promastigotes. A 5:1 (parasite: macrophage) ratio was used for the assays. RESULTS: Δlpg2 parasites showed a significant reduction in intracellular parasite load and viability compared to the WT strain. In the early moments of infection, Δlpg2 parasites preferentially entered through the cell body, whereas WT parasites predominantly interacted via the flagellar tip. Mutants also exhibited greater colocalization with acidified intracellular compartments and increased production of reactive oxygen species (ROS), with no significant differences in nitrite levels, an indirect marker of nitric oxide (NO) production. CONCLUSION: The results indicate that the lpg2 gene of L. amazonensis is crucial for the success of infection in C57BL/6 macrophages, since its absence compromises parasite viability during the interaction with the host cell. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Dissertação Fri, 15 Aug 2025 00:00:00 GMT https://repositorio.ufba.br/handle/ri/43888 2025-08-15T00:00:00Z https://repositorio.ufba.br/handle/ri/43864 Título: Identificação e avaliação do potencial citotóxico de fármacos candidatos ao reposicionamento em carcinoma oral de células escamosas Autor(es): Souza, Marina Silva Rodrigues de Primeiro Orientador: Rocha, Clarissa Araújo Gurgel Abstract: INTRODUCTION: Oral Squamous Cell Carcinoma (OSCC) remains a significant public health concern. Despite advances in treatments, including surgery, and chemotherapy, choices remain limited, underscoring the need for innovative therapeutic strategies. Developing new drugs is both costly and time-intensive. Drug repurposing offers a compelling solution by leveraging existing, well-characterized medications that are already approved and toxicologically safe. OBJECTIVE: Identify promising candidates for repositioning in OSCC, through combined integrated in silico analyses tools based on molecular and genetic insights with in vitro cytotoxicity screening based on bi- (2D) and three-dimensional (3D) models. MATERIALS AND METHODS: A total of 237 drug candidates were retrieved from DrugBank to identify druggable targets. Ranking was based on cancer-related pathways and protein-protein interaction centrality. The in vitro cytotoxicity of selected compounds was evaluated in OSCC cell lines (HSC-3, H357) following the National Cancer Institute (NCI) Developmental Therapeutics Program (DTP) guidelines, with CellTiter-Glo® as the viability assay. Homotypic OSCC spheroids were generated using optimized magnetic 3D bioprinting. After ranking, 21 compounds were selected and underwent single-dose screening (10 μM). H357 cells were more sensitive than HSC3, showing lower viability across multiple compounds. Three most promising candidates (Daunorubicin, Erlotinib, and Romidepsin), which displayed growth inhibition properties (at least a 35% reduction), advanced to five-dose screening assays in both 2D and 3D models. In 2D cultures, Romidepsin exhibited the strongest cytotoxic effect, with the lowest IC50 values in both cell lines. In 3D assays, all three drugs demonstrated cytotoxic activity, with Romidepsin once again emerging as the most potent compound. RESULTS: The ranking strategy accelerated candidate selection and increased the chances of success by focusing on targets that exert greater influence on pathways relevant to OSCC. HSC-3 cells, known for higher tumorigenic potential, exhibited greater drug resistance than H357. Different mechanisms of action that maximize the therapeutic applications of the selected drugs were found. They include epidermal growth factor receptor (EGFR) inhibition, topoisomerase II inhibition, and a potent class I histone deacetylase (HDAC) blocker. Differences in 2D and 3D responses highlight the need for physiologically relevant models to improve translational relevance. CONCLUSIONS: These findings reinforce the value of drug repurposing as an efficient strategy for expanding OSCC treatment options. By integrating computational approaches with physiologically relevant 3D models, this approach paves the way for more precise and personalized cancer therapies. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Dissertação Fri, 13 Dec 2024 00:00:00 GMT https://repositorio.ufba.br/handle/ri/43864 2024-12-13T00:00:00Z https://repositorio.ufba.br/handle/ri/43863 Título: Identificação de biomarcadores de desfecho terapêutico utilizando dados públicos de transcriptomas da leishmaniose cutânea Autor(es): Amaral, Raissa Vieira do Primeiro Orientador: Tavares, Natalia Machado Abstract: INTRODUCTION: Leishmaniasis is an infectious disease of global importance, characterized by ulcerative lesions with raised borders and exacerbated inflammation. The main first-line therapy, pentavalent antimony (Sb⁵⁺), has limited efficacy, with frequent treatment failure rates. In this context, transcriptomic analyses have emerged as promising tools for identifying biomarkers with predictive potential for treatment response. OBJECTIVE: This study aimed to compare transcriptional signatures from different public datasets obtained from biopsies of patients with cutaneous leishmaniasis caused by Leishmania braziliensis, followed by ex vivo validation. METHODS: Data were obtained from the repositories GSE214397 and GSE127831 (RNA-Seq, Illumina platform) and GSE55664 (microarray, Illumina platform), comparing gene expression between patients who were cured and those who experienced treatment failure with Sb⁵⁺. Subsequently, biopsies from lesions of a new clinical cohort were analyzed by RT-qPCR. Analyses included differential gene expression, correlation with clinical parameters (healing time, DTH, lesion size), ROC curve, and logistic regression. RESULTS: Exploratory analysis of GSE214397 identified ten differentially expressed genes, whose expression was correlated with treatment outcomes. Among these, two genes stood out: CCL7 and RETN, whose expression was strongly associated with therapeutic failure. These findings were validated in the new cohort by RT-qPCR. CONCLUSION: The CCL7 and RETN genes were identified as promising candidates for biomarkers of treatment failure in cutaneous leishmaniasis, with potential clinical application. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Dissertação Thu, 03 Jul 2025 00:00:00 GMT https://repositorio.ufba.br/handle/ri/43863 2025-07-03T00:00:00Z