Cell Biology, Biochemistry, Genetics and Molecular Biology, Immunology and Microbiology, Multidisciplinary
27
Scopus Publications
Scopus Publications
Arachidonic Acid Metabolism and HETEs-PGs Imbalance in L. infantum Infection: Implications for Visceral Leishmaniasis Progression Yasmin Monara Ferreira de Sousa Andrade, Astrid Madeleine Calero Goicochea, Flávio Henrique Jesus-Santos, Jonathan Luís Magalhães Fontes, Bianca Ramos Mesquita, Caroline Vilas Boas deMelo, Nicole Hlavac, Icaro Bonyek-Silva, Manuela da Silva Solcà, Deborah Bittencourt Mothé Fraga, Adriana Ferreira Lopes Vilela, Carlos Arterio Sorgi, Washington Luis Conrado dos Santos, Théo Araújo-Santos, Valeria M. Borges ACS Omega, 2025 Visceral leishmaniasis (VL) alters lipid metabolism, impacting the production of bioactive compounds like eicosanoids, which regulate inflammation─a key aspect of the disease. This study investigated eicosanoid production in Golden Syrian hamsters infected with Leishmania infantum for five months. The infected animals developed splenomegaly, increased creatinine, elevated liver transaminases, granulomas, white pulp hypoplasia, and portal infiltrates. Arachidonic acid (AA) mobilization was elevated in the spleen and liver but unchanged in plasma. Liquid chromatography mass spectrometry (LC–MS/MS) analysis revealed increased hydroxyeicosatetraenoic acids (HETEs) in the spleen, while prostaglandin (PG) E2, 2-keto-PGE2, and PGD2 were reduced. Notably, splenomegaly, higher HETEs, and lower PGs levels correlated with parasite load, suggesting L. infantum manipulates these mediators to promote inflammation and its persistence. The imbalance between HETEs and PGs seems crucial for VL progression, highlighting the need for further research into the mechanisms driving disease pathogenesis.
Activation Pathways of Murine Macrophages by Lipophosphoglycan from Strains of Leishmania major (FV1 and LV39) Vanessa Mançur Santos, Astrid Madeleine Calero Goicochea, Antônio José Soares Neto, Flávio Henrique Jesus Santos, Jéssica Lobo da Silva, Théo Araújo-Santos, Leonardo Paiva Farias, Claudia Ida Brodskyn, Valéria M. Borges, Rodrigo Pedro Soares, Jonilson Berlink Lima ACS Infectious Diseases, 2024 High Resolution Image Download MS PowerPoint Slide Lipophosphoglycan (LPG) is an important Leishmania virulence factor. It is the most abundant surface glycoconjugate in promastigotes, playing an important role in the interaction with phagocytic cells. While LPG is known to modulate the macrophage immune response during infection, the activation mechanisms triggered by this glycoconjugate have not been fully elucidated. This work investigated the role that LPGs purified from two strains of Leishmania major (FV1 and LV39) play in macrophage activation, considering the differences in their biochemical structures. Bone marrow-derived macrophages from BALB/c mice were stimulated with 10 μg/mL purified LPG from the LV39 and FV1 strains. We then measured the production of nitric oxide (NO) and cytokines, the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and the activation of MAPK pathways. LPG from the LV39 strain, which has longer poly-galactosylated side chains, induced a more pro-inflammatory profile than that from the FV1 strain. This included higher production of NO, TNF-α, and PGE2, and increased expression of COX-2 and iNOS. Additionally, the phosphorylation of ERK-1/2 and JNK was elevated in macrophages exposed to LPG from the LV39 strain. No difference in IL-10 production was observed in cells stimulated by both LPG. Thus, intraspecific structural differences in LPG contribute to distinct innate immune responses in macrophages.
Identification of cases of color blindness in the academic community: Implications for teaching-learning Ítalo Ramon Bessa Holanda, Théo Araújo-Santos Medicina Brazil, 2024 Introdução: O daltonismo continua sendo uma condição negligenciada nos ambientes educacionais e não existem dados disponíveis sobre prevalência e características dos casos no contexto acadêmico. No ensino superior, há carência de dados sobre as limitações impostas pela condição, assim como sobre a predileção de indivíduos daltônicos pelas diferentes áreas de conhecimento. Métodos: Neste trabalho, foi realizado um estudo de série de casos de daltonismo na comunidade acadêmica de Barreiras, Bahia, Brasil, onde os casos foram identificados por meio do teste online de Ishihara associado ao interrogatório sintomatológico em um único questionário digital. Resultados: A prevalência de daltonismo dentro da população do estudo foi de 6,35% (15/256) dos participantes. Foi observada uma maior concentração de casos dentre participantes que são da área de conhecimento da saúde. Embora alguns portadores de daltonismo tenham relatado um prejuízo no seu processo de aprendizagem, os achados indicam que esta não foi uma condição determinante para a escolha de área de conhecimento, porém limita a escolha de atuação em áreas específicas. A associação de um inquérito sintomatológico permitiu identificar casos de daltonismo não distinguíveis pelo teste online de Ishihara e, embora considerados raros, nós identificamos casos de tritanomalia entre os participantes do estudo. Conclusões: Desta forma, os dados apontam a presença de casos de daltonismo na comunidade acadêmica de Barreiras no oeste da Bahia e sugere que estudos adicionais devem ser conduzidos para traçar um perfil mais amplo sobre as consequências do daltonismo nos processos de ensino-aprendizagem no ensino superior.
Polyunsaturated fatty acids alter the formation of lipid droplets and eicosanoid production in Leishmania promastigotes Yasmin Monara Ferreira de Sousa Andrade, Monara Viera de Castro, Victor de Souza Tavares, Rayane da Silva Oliveira Souza, Lúcia Helena Faccioli, Jonilson Berlink Lima, Carlos Arterio Sorgi, Valéria M Borges, Théo Araújo-Santos Memorias do Instituto Oswaldo Cruz, 2023 BACKGROUND: The knowledge about eicosanoid metabolism and lipid droplet (LD) formation in the Leishmania is very limited and new approaches are needed to identify which bioactive molecules are produced of them. OBJECTIVES: Herein, we compared LDs and eicosanoids biogenesis in distinct Leishmania species which are etiologic agents of different clinical forms of leishmaniasis. METHODS: For this, promastigotes of Leishmania amazonensis, L. braziliensis and L. infantum were stimulated with polyunsaturated fatty acids (PUFA) and LD and eicosanoid production was evaluated. We also compared mutations in structural models of human-like cyclooxygenase-2 (GP63) and prostaglandin F synthase (PGFS) proteins, as well as the levels of these enzymes in parasite cell extracts. FINDINGS: PUFAs modulate the LD formation in L. braziliensis and L. infantum. Leishmania spp with equivalent tissue tropism had same protein mutations in GP63 and PGFS. No differences in GP63 production were observed among Leishmania spp, however PGFS production increased during the parasite differentiation. Stimulation with arachidonic acid resulted in elevated production of hydroxyeicosatetraenoic acids compared to prostaglandins. MAIN CONCLUSIONS: Our data suggest LD formation and eicosanoid production are distinctly modulated by PUFAS dependent of Leishmania species. In addition, eicosanoid-enzyme mutations are more similar between Leishmania species with same host tropism.
Identifying Inconclusive Data in the SARS-CoV-2 Molecular Diagnostic Using Nucleocapsid Phosphoprotein Gene as a Target Raphael Contelli Klein, Mary Hellen Fabres Klein, Larissa Gomes Barbosa, Lívia Vasconcelos Gonzaga Knnup, Larissa Paola Rodrigues Venâncio, Jonilson Berlink Lima, Théo Araújo-Santos Archives of Pathology and Laboratory Medicine, 2022 Context.— The gold standard test to identify the presence of SARS-CoV-2 in COVID-19 patients is the real-time reverse transcription–quantitative polymerase chain reaction (RT-qPCR), but inconclusive data and false-positive diagnosis remain the major problem of this approach. Objective.— To compare the fitness of 2 primer sets to the SARS-CoV-2 nucleocapsid phosphoprotein gene (NP) in the molecular diagnosis of COVID-19, we verified the inconclusive data and confidence of high cycle threshold (Ct) values in SARS-CoV-2 detection. Design.— The 970 patient samples were tested by using United States Centers for Disease Control and Prevention protocol. We compared the fitness of 2 primer sets to 2 different regions of the NP gene. In addition, we checked the consistency of positive samples with high Ct values by retesting extracted SARS-CoV-2 RNA or by second testing of patients. Results.— N1 and N2 displayed similar fitness during testing, with no differences between Ct values. Then, we verified security range Ct values related to positive diagnostics, with Ct values above 34 failing in 21 of 32 cases (65.6%) after retesting of samples. The patient samples with Ct values above 34.89 that were doubly positive revealed a low sensitivity (52.4%) and specificity (63.6%) of the test in samples with Ct values above 34. Conclusions.— It is safe to use 1 primer set for the NP gene to identify SARS-CoV-2 in samples. However, samples with high Ct values may be considered inconclusive and retested to avoid false-positive diagnosis.
Coagulopathy and the humoral response against viral proteins in patients at different stages of COVID-19 Fernanda Pereira Monteiro, Victor de Souza Tavares, Rayane da Silva Oliveira Souza, Larissa Paola Rodrigues Venâncio, Mary Hellen Fabres-Klein, Rodrigo Feliciano do Carmo, Raphael Contelli Klein, Jonilson Berlink Lima, Théo Araújo-Santos Memorias do Instituto Oswaldo Cruz, 2022 BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) often present with coagulopathies and have high titres of circulating antibodies against viral proteins. OBJECTIVES: Herein, we evaluated the association between D-dimer and circulating immunoglobulin levels against viral proteins in patients at different clinical stages of COVID-19. METHODS: For this, we performed a cross-sectional study involving patients of the first wave of COVID-19 clinically classified as oligosymptomatic (n = 22), severe (n = 30), cured (n = 27) and non-infected (n = 9). Next, we measured in the plasma samples the total and fraction of immunoglobulins against the nucleoprotein (NP) and the receptor-binding domain (RBD) of the spike proteins by enzyme-linked immunosorbent assay (ELISA) assays. FINDINGS: Patients with severe disease had a coagulation disorder with high levels of D-dimer as well as circulating IgG against the NP but not the RBD compared to other groups of patients. In addition, high levels of D-dimer and IgG against the NP and RBD were associated with disease severity among the patients in this study. MAIN CONCLUSIONS: Our data suggest that IgG against NP and RBD participates in the worsening of COVID-19. Although the humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is partially understood, and more efforts are needed to clarify gaps in the knowledge of this process.
Lipid droplets from protozoan parasites: Survival and pathogenicity Victor de Souza Tavares, Monara Viera de Castro, Rayane da Silva Oliveira Souza, Iana Kátia Araújo Gonçalves, Jonilson Berlink Lima, Valéria de Matos Borges, Théo Araújo-Santos Memorias do Instituto Oswaldo Cruz, 2021 Lipid droplets (LDs; lipid bodies) are intracellular sites of lipid storage and metabolism present in all cell types. Eukaryotic LDs are involved in eicosanoid production during several inflammatory conditions, including infection by protozoan parasites. In parasites, LDs play a role in the acquisition of cholesterol and other neutral lipids from the host. The number of LDs increases during parasite differentiation, and the biogenesis of these organelles use specific signaling pathways involving protein kinases. In addition, LDs are important in cellular protection against lipotoxicity. Recently, these organelles have been implicated in eicosanoid and specialised lipid metabolism. In this article, we revise the main functions of protozoan parasite LDs and discuss future directions in the comprehension of these organelles in the context of pathogen virulence.
Associations between TGF- β 1 Levels and Markers of Hemolysis, Inflammation, and Tissue Remodeling in Pediatric Sickle Cell Patients Rayra P. Santiago, Magda O. S. Carvalho, Camylla V. B. Figueiredo, Luciana M. Fiuza, Rodrigo M. Oliveira, Sètondji C. M. A. Yahouédéhou, Valma M. L. Nascimento, Isa M. Lyra, Théo Araujo-Santos, Nívea F. Luz, Milena M. Aleluia, Caroline C. Guarda, Valéria M. Borges, Marilda S. Goncalves Mediators of Inflammation, 2021 Transforming growth factor beta (TGF‐β) is a cytokine with important involvement in biological processes related to the pathogenesis of sickle cell disease (SCD), including endothelial and vascular dysfunction, inflammation, and hematopoietic homeostasis. This study is aimed at investigating associations between levels of TGF‐β1 and classical laboratory biomarkers and inflammatory mediators, as well as the tissue inhibitor of metalloproteases‐1 (TIMP‐1) and matrix metalloproteinase‐9 (MMP‐9), in pediatric patients (n = 123) with SCD in steady state: 84 with sickle cell anemia (HbSS) and 39 with hemoglobin SC disease (HbSC). A healthy control (HC) group of 59 individuals was also included. Hematological and biochemical analyses were carried out using electronic methods. TGF‐β1, TIMP‐1, and MMP‐9 plasma quantifications were performed by ELISA. TGF‐β1 plasma levels were higher in HbSS individuals than in HbSC and HC. In individuals with HbSS, TGF‐β1 levels were positively correlated with red blood cells, hemoglobin, hematocrit, platelets, and TIMP‐1. In addition, HbSS individuals with TGF‐β1 levels above the median (≥72.29 ng/mL) also presented increased monocyte counts and decreased albumin levels. In patients with HbSC, TGF‐β1 levels were positively correlated with leukocytes, eosinophils, lymphocytes, monocytes, and platelets, as well as levels of TIMP‐1, VLDL‐C, triglycerides, heme, and AST. Additionally, HbSC individuals with TGF‐β1 levels above the median (≥47.80 ng/mL) presented increased leukocyte and platelet counts, as well as increased levels of triglycerides, VLDL‐C, MMP‐9, and TIMP‐1, and decreased HDL‐C. Our findings suggest that TGF‐β1 may play important roles in vascular remodeling, vasculopathy, angiogenesis, and inflammation in pediatric patients with SCD.
Leishmania infantum lipophosphoglycan-deficient mutants: A tool to study host cell-parasite interplay Milena Lázaro-Souza, Christine Matte, Jonilson B. Lima, Guillermo Arango Duque, Graziele Quintela-Carvalho, Áislan de Carvalho Vivarini, Sara Moura-Pontes, Cláudio P. Figueira, Flávio H. Jesus-Santos, Ulisses Gazos Lopes, Leonardo P. Farias, Théo Araújo-Santos, Albert Descoteaux, Valéria M. Borges Frontiers in Microbiology, 2018
COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease Jamary Oliveira-Filho, Ana C.P. Ornellas, Cathy R. Zhang, Luciana M.B. Oliveira, Théo Araújo-Santos, Valeria M. Borges, Laís M.G.B. Ventura, Francisco J.F.B. Reis, Roque Aras, André M. Fernandes, Jonathan Rosand, Steven M. Greenberg, Karen L. Furie, Natalia S. Rost Journal of Stroke and Cerebrovascular Diseases, 2015
Heme oxygenase-1 promotes the persistence of Leishmania chagasi infection Nívea F Luz, Bruno B Andrade, Daniel F Feijó, Théo Araújo-Santos, Graziele Q Carvalho, Daniela Andrade, Daniel R Abánades, Enaldo V Melo, Angela M Silva, Cláudia I Brodskyn, Manoel Barral-Netto, Aldina Barral, Rodrigo P Soares, Roque P Almeida, Marcelo T Bozza, Valéria M Borges Journal of Immunology, 2012
Lutzomyia longipalpis saliva drives apoptosis and enhances parasite burden in neutrophils Deboraci Brito Prates, Théo Araújo-Santos, Nívea Farias Luz, Bruno B Andrade, Jaqueline França-Costa, Lilian Afonso, Jorge Clarêncio, José Carlos Miranda, Patrícia T Bozza, George A DosReis, Cláudia Brodskyn, Manoel Barral-Netto, Valéria de Matos Borges, Aldina Barral Journal of Leukocyte Biology, 2011