EMERSON SOARES BERNARDES

EMERSON SOARES BERNARDES

(Fonte: Lattes)

Resumo

Bachelor's at Farmácia from Universidade Federal de Ouro Preto (1998) and doctorate at Applied Imunology from Universidade de São Paulo (2004). Has experience in Medicine, acting on the following subjects: galectina-3, carboidratos, trypanosoma cruzi, carcinogênesis and macrophage. (Text obtained from the Currículo Lattes on October 8th 2021)

Possui graduação em Farmácia pela Universidade Federal de Ouro Preto (1998), mestrado e doutorado em Imunologia Básica e Aplicada pela Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (2004), com período de Doutorado Sanduíche pela Universidade da California, Davis, USA. Realizou pós-doutoramento durante o período de 2004 a 2008 pela Faculdade de Medicina da USP-Ribeirão Preto. Trabalhou como pesquisador contratado pelo Instituto de Patologia e Imunologia Molecular da Universidade do Porto - IPATIMUP em Portugal no período de 2008 a 2011. Retornou ao Brasil como pesquisador visitante na Faculdade de Medicina da USP - São Paulo (2011-2012) e foi posteriormente contratado como pesquisador no Instituto do Câncer do Estado de São Paulo (2012-2013). Coordenou um projeto Jovem Pesquisador financiado pela FAPESP (2012-2016 - Desenvolvimento e Produção de Radiofármacos Emissores de Pósitrons com Aplicações Diagnósticas em Oncologia) e está integrado como pesquisador Colaborador no Instituto de Pesquisas Energéticas e Nucleares (IPEN). Tem atuado na área da Glicobiologia, com ênfase na participação de proteínas ligantes de carboidratos em processos inflamatórios e no Câncer. Atualmente é professor do Programa de Pós-Graduação do IPEN-USP Tecnologia Nuclear - Aplicações, tem experiência na área de Radiofarmácia, com ênfase no desenvolvimento de Radiofármacos inéditos para diagnóstico e terapia em Oncologia. (Texto extraído do Currículo Lattes em 08 out. 2021)

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Recognition of breast cancer subtypes using FTIR hyperspectral data
2024 - FAROOQ, SAJID; DEL-VALLE, MATHEUS; SANTOS, SOFIA N. dos; BERNARDES, EMERSON S.; ZEZELL, DENISE M.
Fourier -transform infrared spectroscopy (FTIR) is a powerful, non-destructive, highly sensitive and a promising analytical technique to provide spectrochemical signatures of biological samples, where markers like carbohydrates, proteins, and phosphate groups of DNA can be recognized in biological micro -environment. However, method of measurements of large cells need an excessive time to achieve high quality images, making its clinical use difficult due to speed of data -acquisition and lack of optimized computational procedures. To address such challenges, Machine Learning (ML) based technologies can assist to assess an accurate prognostication of breast cancer (BC) subtypes with high performance. Here, we applied FTIR spectroscopy to identify breast cancer subtypes in order to differentiate between luminal (BT474) and nonluminal (SKBR3) molecular subtypes. For this reason, we tested multivariate classification technique to extract feature information employing three -dimension (3D) -discriminant analysis approach based on 3D -principle component analysis -linear discriminant analysis (3D-PCA-LDA) and 3D -principal component analysis -quadratic discriminant analysis (3D-PCA-QDA), showing an improvement in sensitivity (98%), specificity (94%) and accuracy (98%) parameters compared to conventional unfolded methods. Our results evidence that 3D-PCALDA and 3D-PCA-QDA are potential tools for discriminant analysis of hyperspectral dataset to obtain superior classification assessment.
Plant-derived polyphenolic compounds
2023 - ROSALES, THIECLA K.O.; SILVA, FABIO F.A. da; BERNARDES, EMERSON S.; FABI, JOAO P.
Plant-derived polyphenols are naturally occurring compounds widely distributed in plants. They have received greater attention in the food and pharmaceutical industries due to their potential health benefits, reducing the risk of some chronic diseases due to their antioxidant, anti-inflammatory, anticancer, cardioprotective, and neuro-action properties. Polyphenolic compounds orally administered can be used as adjuvants in several treatments but with restricted uses due to chemical instability. The review discusses the different structural compositions of polyphenols and their influence on chemical stability. Despite the potential and wide applications, there is a need to improve the delivery of polyphenolics to target the human intestine without massive chemical modifications. Oral administration of polyphenols is unfeasible due to instability, low bioaccessibility, and limited bioavailability. Nano-delivery systems based on polysaccharides (starch, pectin, chitosan, and cellulose) have been identified as a viable option for oral ingestion, potentiate biological effects, and direct-controlled delivery in specific tissues. The time and dose can be individualized for specific diseases, such as intestinal cancer. This review will address the mechanisms by which polysaccharides-based nanostructured systems can protect against degradation and enhance intestinal permeation, oral bioavailability, and the potential application of polysaccharides as nanocarriers for the controlled and targeted delivery of polyphenolic compounds.
Synthesis, biological evaluation and molecular docking studies of novel 1,2,3-triazole-quinazolines as antiproliferative agents displaying ERK inhibitory activity
2021 - NUNES, PAULO S.G.; SILVA, GABRIEL da; NASCIMENTO, SOFIA; MANTOANI, SUSIMAIRE P.; ANDRADE, PETERSON de; BERNARDES, EMERSON S.; KAWANO, DANIEL F.; LEOPOLDINO, ANDREIA M.; CARVALHO, IVONE
ERK1/2 inhibitors have attracted special attention concerning the ability of circumventing cases of innate or log-term acquired resistance to RAF and MEK kinase inhibitors. Based on the 4-aminoquinazoline pharmacophore of kinases, herein we describe the synthesis of 4-aminoquinazoline derivatives bearing a 1,2,3-triazole stable core to bridge different aromatic and heterocyclic rings using copper-catalysed azide-alkyne cycloaddition reaction (CuAAC) as a Click Chemistry strategy. The initial screening of twelve derivatives in tumoral cells (CAL-27, HN13, HGC-27, and BT-20) revealed that the most active in BT-20 cells (25a, IC50 24.6 μM and a SI of 3.25) contains a more polar side chain (sulfone). Furthermore, compound 25a promoted a significant release of lactate dehydrogenase (LDH), suggesting the induction of cell death by necrosis. In addition, this compound induced G0/G1 stalling in BT-20 cells, which was accompanied by a decrease in the S phase. Western blot analysis of the levels of p-STAT3, p-ERK, PARP, p53 and cleaved caspase-3 revealed p-ERK1/2 and p-STA3 were drastically decreased in BT-20 cells under 25a incubation, suggesting the involvement of these two kinases in the mechanisms underlying 25a-induced cell cycle arrest, besides loss of proliferation and viability of the breast cancer cell. Molecular docking simulations using the ERK-ulixertinib crystallographic complex showed compound 25a could potentially compete with ATP for binding to ERK in a slightly higher affinity than the reference ERK1/2 inhibitor. Further in silico analyses showed comparable toxicity and pharmacokinetic profiles for compound 25a in relation to ulixertinib.
Novel sterile insect technology program results in suppression of a field mosquito population and subsequently to reduced incidence of dengue
2021 - PONCIO, LISIANE de C.; ANJOS, FILIPE A. dos; OLIVEIRA, DEBORAH A. de; REBECHI, DEBORA; OLIVEIRA, RODRIGO N. de; CHITOLINA, RODRIGO F.; FERMINO, MARISE L.; BERNARDES, LUCIANO G.; GUIMARAES, DANTON; LEMOS, PEDRO A.; SILVA, MARCELO N.E.; SILVESTRE, RODRIGO G.M.; BERNARDES, EMERSON S.; PALDI, NITZAN
Background. There is a steady rise in the global incidence of Aedes-borne arbovirus disease. It has become urgent to develop alternative solutions for mosquito vector control. We developed a new method of sterilization of male mosquitoes with the goal to suppress a local Aedes aegypti population and to prevent the spread of dengue. Methods. Sterile male mosquitoes were produced from a locally acquired Ae. aegypti colony by using a treatment that includes doublestranded RNA and thiotepa. A field study was conducted with sterile mosquito releases being performed on a weekly basis in predefined areas. There were 2 intervention periods (INT1 and INT2), with treatment and control areas reversed between INT1 and INT2. Results. During INT1, releases in the treated area resulted in up to 91.4% reduction of live progeny of field Ae. aegypti mosquitoes recorded over time, while the control neighborhoods (no releases of sterile male mosquitoes) remained highly infested. The successful implementations of the program during INT1 and INT2 were associated with 15.9-fold and 13.7-fold lower incidences of dengue in the treated area compared to the control areas, respectively. Conclusions. Our data show the success of this new sterile insect technology-based program in preventing the spread of dengue.
Galectin-3 orchestrates the histology of mesentery and protects liver during lupus-like syndrome induced by pristane
2019 - LEMOS, F.S.; PEREIRA, J.X.; CARVALHO, V.F.; BERNARDES, E.S.; CHAMMAS, R.; PEREIRA, T.M.; CARVALHO, R.S.; LUISETTO, R.; EL-CHEIKH, M.C.; CALIL-ELIAS, S.; OLIVEIRA, F.L.
Galectin-3 (Gal-3) controls intercellular and cell-extracellular matrix interactions during immunological responses. In chronic inflammation, Gal-3 is associated with fibrotic events, regulates B cell differentiation and delays lupus progression. Gal-3 deficient mice (Lgals3−/−) have intense germinal center formation and atypical plasma cell generation correlated to high levels IgG, IgE, and IgA. Here, we used pristane (2,6,10,14-tetramethylpentadecane) to induce lupus-like syndrome in Lgals3−/− and Lgals3+/+ BALB/c mice. Mesentery and peritoneal cells were monitored because promptly react to pristane injected in the peritoneal cavity. For the first time, mesenteric tissues have been associated to the pathogenesis of experimental lupus-like syndrome. In Lgals3+/+ pristane-induced mice, mesentery was hallmarked by intense fibrogranulomatous reaction restricted to submesothelial regions and organized niches containing macrophages and B lymphocytes and plasma cells. In contrast, Lgals3−/− pristane-treated mice had diffuse mesenteric fibrosis affecting submesothelium and peripheral tissues, atypical M1/M2 macrophage polarization and significant DLL1+ cells expansion, suggesting possible involvement of Notch/Delta pathways in the disease. Early inflammatory reaction to pristane was characterized by significant disturbances on monocyte recruitment, macrophage differentiation and dendritic cell (DC) responses in the peritoneal cavity of pristane-induced Lgals3−/− mice. A correlative analysis showed that mesenteric damages in the absence of Gal-3 were directly associated with severe portal inflammation and hepatitis. In conclusion, it has suggested that Gal-3 orchestrates histological organization in the mesentery and prevents lupoid hepatitis in experimental lupus-like syndrome by controlling macrophage polarization, Notch signaling pathways and DC differentiation in mesenteric structures.
In loco retention effect of magnetic core mesoporous silica nanoparticles doped with trastuzumab as intralesional nanodrug for breast cancer
2018 - PORTILHO, FILIPE L.; PINTO, SUYENE R.; BARROS, ALINE O. da S. de; HELAL-NETO, EDWARD; SANTOS, SOFIA N. dos; BERNARDES, EMERSON S.; ILEM-OZDEMIR, DERYA; ASIKOGLU, MAKBULE; ALENCAR, LUCIANA M.R.; SANTOS, CLENILTON C. dos; RICCI-JUNIOR, EDUARDO; SANCENON, FELIX; MARTINEZ-MANEZ, RAMON; SANTOS-OLIVEIRA, RALPH
Breast cancer is women’s most common type of cancer, with a global rate of over 522,000 deaths per year. One of the main problems related to breast cancer relies in the early detection, as the specialized treatment. In this direction was developed, characterized and tested in vivo a smart delivery system, based on radiolabelled magnetic core mesoporous silica doped with trastuzumab as intralesional nanodrug for breast cancer imaging and possible therapy. The results showed that nanoparticles had a size of 58.9 ± 8.1 nm, with specific surface area of 872 m2/g and pore volume of 0.85 cm3/g with a pore diameter of 3.15 nm. The magnetic core mesoporous silica was efficiently labelled with 99mTc (97.5% ±0.8) and doped >98%. The cytotoxicity assay, demonstrated they are safe to use. The data were corroborated with the IC50 result of: 829.6 mg ± 43.2. The biodistribution showed an uptake by the tumour of 7.5% (systemic via) and 97.37% (intralesional) with less than 3% of these nanoparticles absorbed by healthy tissues. In a period 6-h post-injection, no barrier delimited by the tumour was crossed, corroborating the use as intralesional nanodrug.
Transcriptomic and functional analyses of the piRNA pathway in the Chagas disease vector Rhodnius prolixus
2018 - BRITO, TARCISIO; JULIO, ALISON; BERNI, MATEUS; PONCIO, LISIANE de C.; BERNARDES, EMERSON S.; ARAUJO, HELENA; SAMMETH, MICHAEL; PANE, ATTILIO
The piRNA pathway is a surveillance system that guarantees oogenesis and adult fertility in a range of animal species. The pathway is centered on PIWI clade Argonaute proteins and the associated small non-coding RNAs termed piRNAs. In this study, we set to investigate the evolutionary conservation of the piRNA pathway in the hemimetabolous insect Rhodnius prolixus. Our transcriptome profiling reveals that core components of the pathway are expressed during previtellogenic stages of oogenesis. Rhodnius' genome harbors four putative piwi orthologs. We show that Rp-piwi2, Rp-piwi3 and Rp-ago3, but not Rp-piwi1 transcripts are produced in the germline tissues and maternally deposited in the mature eggs. Consistent with a role in Rhodnius oogenesis, parental RNAi against the Rp-piwi2, Rp-piwi3 and Rp-ago3 results in severe egg laying and female adult fertility defects. Furthermore, we show that the reduction of the Rp-piwi2 levels by parental RNAi disrupts oogenesis by causing a dramatic loss of trophocytes, egg chamber degeneration and oogenesis arrest. Intriguingly, the putative Rp-Piwi2 protein features a polyglutamine tract at its N-terminal region, which is conserved in PIWI proteins encoded in the genome of other Triatomine species. Together with R. prolixus, these hematophagous insects are primary vectors of the Chagas disease. Thus, our data shed more light on the evolution of the piRNA pathway and provide a framework for the development of new control strategies for Chagas disease insect vectors.
Lack of galectin-3 modifies differentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell differentiation
2018 - OLIVEIRA, FELIPE L. de; SANTOS, SOFIA N. dos; RICON, LAUREMILIA; COSTA, THAYSE P. da; PEREIRA, JONATHAS X.; BRAND, CAMILA; FERMINO, MARISE L.; CHAMMAS, ROGER; BERNARDES, EMERSON S.; EL-CHEIKH, MARCIA C.
Galectin-3 (Gal-3) is a beta-galactoside binding protein that controls cell-cell and cell-extracellular matrix interactions. In lymphoid organs, gal-3 inhibits B cell differentiation by mechanisms poorly understood. The B cell development is dependent on tissue organization and stromal cell signaling, including IL-7 and Notch pathways. Here, we investigate possible mechanisms that gal-3 interferes during B lymphocyte differentiation in the bone marrow (BM) and spleen. The BM of gal-3-deficient mice (Lgals3(-/-)mice) was evidenced by elevated numbers of B220(+)CD19(+)c-Kit(+)IL-7R(+) progenitor B cells. In parallel, CD45-bone marrow stromal cells expressed high levels of mRNA IL-7, Notch ligands (Jagged-1 and Delta-like 4), and transcription factors (Hes-1, Hey-1, Hey-2 and Hey-L). The spleen of Lgals3(-/-)mice was hallmarked by marginal zone disorganization, high number of IgM(+) IgD(+) B cells and CD138(+)plasma cells, overexpression of Notch ligands (Jagged-1, Delta-like 1 and Delta-like 4) by stromal cells and Hey-1. Morever, IgM(+) IgD(+) B cells and B220(+)CD138(+)CXCR4(+) plasmablasts were significantly increased in the BM and blood of Lgals3(-/-)mice. For the first time, we demonstrated that gal-3 inhibits Notch signaling activation in lymphoid organs regulating earlier and terminal events of B cell differentiation.
MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications
2017 - PASCUAL, LLUIS; CERQUEIRA-COUTINHO, CRISTAL; GARCIA-FERNANDEZ, ALBA; LUIS, BEATRIZ de; BERNARDES, EMERSON S.; ALBERNAZ, MARTA S.; MISSAILIDIS, SOTIRIS; MARTINEZ-MANEZ, RAMON; SANTOS-OLIVEIRA, RALPH; ORZAEZ, MAR; SANCENON, FELIX
Mucin 1 (MUC1) is a cell surface protein overexpressed in breast cancer. Mesoporous silica nanoparticles (MSNs) loaded with safranin O, functionalized with aminopropyl groups and gated with the negatively charged MUC1 aptamer have been prepared (S1-apMUC1) for specific targeting and cargo release in tumoral versus non-tumoral cells. Confocal microscopy studies showed that the S1-apMUC1 nanoparticles were internalized in MDA-MB-231 breast cancer cells that overexpress MUC1 receptor with subsequent pore opening and cargo release. Interestingly, the MCF-10-A non-tumorigenic breast epithelial cell line that do not overexpress MUC1, showed reduced (S1- apMUC1) internalization. Negligible internalization was also found for S1-ap nanoparticles that contained a scrambled DNA sequence as gatekeeper. S2-apMUC1 nanoparticles (similar to S1-apMUC1 but loaded with doxorubicin) internalized in MDA-MB-231 cells and induced a remarkable reduction in cell viability. Moreover, S1-apMUC1 nanoparticles radio-labeled with 99mTc (S1-apMUC1-Tc) showed a remarkable tumor targeting in in vivo studies with MDA-MB-231 tumor-bearing Balb/c mice. © 2017 Elsevier Inc. All rights reserved.
Diagnosing lung cancer using etoposide microparticles labeled with 99mTc
2018 - SALVI, ROBERTO; CERQUEIRA-COUTINHO, CRISTAL; RICCI-JUNIOR, EDUARDO; SANTOS, SOFIA N. dos; PINTO, SUYENE R.; BERNARDES, EMERSON S.; ARAUJO, PATRICIA L.B. de; SANTOS-OLIVEIRA, RALPH
The diagnosis of lung cancer mostly occurs when the cancer is already in an advanced stage. In this situation, there are few options for the treatment and most of them have few chances of success. In this study, we developed and tested etoposide microparticles as a diagnostic agent for imaging lung cancer at early stages of development. We tested etoposide microparticles labeled with technetium 99m in inducted mice. The results demonstrated that over 10% of the total dose used was uptake by the tumor site. Also, the results showed that the microparticles had a good renal clearance and low uptake by liver and spleen. The data suggest that these micro-radiopharmaceuticals may be used for lung cancer imaging exam, especially single-photo emission computed tomography (SPECT).