450 results on '"João Santana da Silva"'
Search Results
2. Dataset of dual RNA-seq mapping in visceral leishmaniasis: Inquiry on parasite transcripts in human blood transcriptome upon Leishmania infantum infection
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Ellen Gomes, Luana Aparecida Rogerio, Nayore Tamie Takamiya, Caroline Torres, João Santana da Silva, Roque Pacheco Almeida, and Sandra Regina Maruyama
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Dual RNA-seq ,Host/parasite interaction ,Leishmania ,Leishmaniasis ,blood transcriptomics ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Science (General) ,Q1-390 - Abstract
This dataset is related to the article “Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection” by S.R. Maruyama, C.A. Fuzo, A.E.R. Oliveira, L.A. Rogerio, N.T. Takamiya, G. Pessenda, E.V. de Melo, A.M. da Silva, A.R. Jesus, V. Carregaro, H.I. Nakaya, R.P. Almeida and J.S. da Silva. Frontiers in Immunology, 2022. Through the reuse of raw sequencing data, we generated original dataset by performing a dual RNA-seq mapping procedure to survey the parasite transcripts found in RNA-seq samples from blood of visceral leishmaniasis patients. Diseased patients with active infection displayed the highest number of reads mapped to L. infantum genome. Even after six months later of the treatment, when the patients were considered cured, parasite reads were still detected. Parasite reads were also detected in asymptomatic individuals. The original dual RNA-seq alignment read count data provided here can be further explored to evaluate either host or parasite transcripts.
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- 2023
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3. Parasite Detection in Visceral Leishmaniasis Samples by Dye-Based qPCR Using New Gene Targets of Leishmania infantum and Crithidia
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Nayore Tamie Takamiya, Luana Aparecida Rogerio, Caroline Torres, João Augusto Franco Leonel, Geovanna Vioti, Tricia Maria Ferreira de Sousa Oliveira, Karoline Camila Valeriano, Gabriane Nascimento Porcino, Isabel Kinney Ferreira de Miranda Santos, Carlos H. N. Costa, Dorcas Lamounier Costa, Tauana Sousa Ferreira, Rodrigo Gurgel-Gonçalves, João Santana da Silva, Felipe Roberti Teixeira, Roque Pacheco De Almeida, José M. C. Ribeiro, and Sandra Regina Maruyama
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visceral leishmaniasis ,molecular diagnosis ,quantitative PCR (qPCR) ,Crithidia sp. LVH60A ,Leishmania infantum ,trypanosomatid co-infection ,Medicine - Abstract
Visceral leishmaniasis (VL) is a neglected disease considered a serious public health problem, especially in endemic countries. Several studies have discovered monoxenous trypanosomatids (Leptomonas and Crithidia) in patients with VL. In different situations of leishmaniasis, investigations have examined cases of co-infection between Leishmania spp. and Crithidia spp. These coinfections have been observed in a wide range of vertebrate hosts, indicating that they are not rare. Diagnostic techniques require improvements and more robust tools to accurately detect the causative agent of VL. This study aimed to develop a real-time quantitative dye-based PCR (qPCR) assay capable of distinguishing Leishmania infantum from Crithidia-related species and to estimate the parasite load in samples of VL from humans and animals. The primer LinJ31_2420 targets an exclusive phosphatase of L. infantum; the primer Catalase_LVH60-12060_1F targets the catalase gene of Crithidia. Therefore, primers were designed to detect L. infantum and Crithidia sp. LVH60A (a novel trypanosomatid isolated from VL patients in Brazil), in samples related to VL. These primers were considered species-specific, based on sequence analysis using genome data retrieved from the TriTryp database and the genome assembling of Crithidia sp. LVH60A strain, in addition to experimental and clinical data presented herein. This novel qPCR assay was highly accurate in identifying and quantifying L. infantum and Crithidia sp. LVH60A in samples obtained experimentally (in vitro and in vivo) or collected from hosts (humans, dogs, cats, and vectors). Importantly, the screening of 62 cultured isolates from VL patients using these primers surprisingly revealed that 51 parasite cultures were PCR+ for Crithidia sp. In addition, qPCR assays identified the co-infection of L. infantum with Crithidia sp. LVH60A in two new VL cases in Brazil, confirming the suspicion of co-infection in a previously reported case of fatal VL. We believe that the species-specific genes targeted in this study can be helpful for the molecular diagnosis of VL, as well as for elucidating suspected co-infections with monoxenous-like trypanosomatids, which is a neglected fact of a neglected disease.
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- 2023
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4. Correlation of TcII discrete typing units with severe chronic Chagas cardiomyopathy in patients from various Brazilian geographic regions.
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Maykon Tavares de Oliveira, Carlos Alessandro Fuzo, Maria Cláudia da Silva, Eduardo Antônio Donadi, João Santana da Silva, Henrique Turin Moreira, André Schmidt, and José Antônio Marin-Neto
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundChagas disease (ChD) is caused by Trypanosoma cruzi. The genetic structure of the species is divided into seven distinct genetic groups, TcI to TcVI, and Tcbat, which have shown differences in terms of geographic distribution, biological properties, and susceptibility to drugs. However, the association between genetic variability and clinical forms of ChD has not yet been fully elucidated. The predominance of TcII and TcVI discrete typing units (DTUs) (genetic groups) is known to occur in several Brazilian regions and is associated with both the domestic and the wild cycles of ChD. Thus, this study aimed to verify the genotypes of the parasites present in 330 patients with chronic Chagas cardiomyopathy (CCC) from different Brazilian states attended at the Clinical Hospital of the Ribeirão Preto Medical School and to assess the existence of a correlation between the clinical forms with the main cardiovascular risk factors and the genetics of the parasite.Methodology principal findingsAll patients with CCC were clinically evaluated through anamnesis, physical examination, biochemical tests, 12-lead electrocardiogram, echocardiogram and chest X-ray. Peripheral blood (5 mL) was collected in guanidine/ethylenediaminetetraacetic acid from each patient for DNA extraction and real-time polymerase chain reaction (PCR) for Chagas disease and genotyping of the parasite in the 7 DTUs. Parasite genotyping was performed using conventional multilocus PCR. Samples of only 175 patients were positive after amplification of the specific genes contained in the T. cruzi genotyping criteria. TcII (64/175), TcVI (9/175), and TcI (3/175) DTUs were predominant, followed by TcII/TcV/TcVI (74/175), and TcII/TcVI (23/175). The TcIII and TcIV DTU´s was detected in only one sample of CCC patients.Conclusions/significanceOur data corroborate previous findings, indicating the predominance of the TcII genotype in patients with CCC of Brazilian origin. Moreover, this study pioneered disclosing a direct correlation between the TcII DTU and severe CCC.
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- 2022
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5. Use of N-acetylcysteine as treatment adjuvant regulates immune response in visceral leishmaniasis: Pilot clinical trial and in vitro experiments
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Lucas Sousa Magalhães, Enaldo Vieira Melo, Nayra Prata Damascena, Adriana Cardoso Batista Albuquerque, Camilla Natália Oliveira Santos, Mônica Cardozo Rebouças, Mariana de Oliveira Bezerra, Ricardo Louzada da Silva, Fabricia Alvisi de Oliveira, Priscila Lima Santos, João Santana da Silva, Michael Wheeler Lipscomb, Ângela Maria da Silva, Amélia Ribeiro de Jesus, and Roque Pacheco de Almeida
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visceral leishmaniasis ,N-acetyl-l-cysteine ,adjuvant chemotherapy ,meglumine antimoniate ,drug therapy ,Microbiology ,QR1-502 - Abstract
This investigation aimed to assess the effect of N-acetylcysteine (NAC) as an adjuvant treatment to alleviate visceral leishmaniasis (VL). The present work includes both blinded randomized clinical intervention and experimental in vitro studies. The clinical trial included 60 patients with VL randomly allocated into two groups: a test group (n = 30) treated with meglumine antimoniate plus NAC (SbV + NAC) and a control group (n = 30) treated with meglumine antimoniate only (SbV). The primary outcome was clinical cure (absence of fever, spleen and liver sizes reduction, and hematological improvement) in 180 days. The cure rate did not differ between the groups; both groups had similar results in all readout indices. The immunological parameters of the patients treated with SbV + NAC showed higher sCD40L in sera during treatment, and the levels of sCD40L were negatively correlated with Interleukin-10 (IL-10) serum levels. In addition, data estimation showed a negative correlation between the sCD40L levels and the spleen size in patients with VL. For the in vitro experiments, peripheral blood mononuclear cells (PBMCs) or PBMC-derived macrophages from healthy donors were exposed to soluble Leishmania antigen (SLA) or infected with stationary promastigotes of Leishmania infantum in the presence or absence of NAC. Results revealed that NAC treatment of SLA-stimulated PBMCs reduces the frequency of monocytes producing IL-10 and lowers the frequency of CD4+ and CD8+ T cells expressing (pro-)inflammatory cytokines. Together, these results suggest that NAC treatment may modulate the immune response in patients with VL, thus warranting additional investigations to support its case use as an adjuvant to antimony therapy for VL.
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- 2022
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6. Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection
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Sandra Regina Maruyama, Carlos Alessandro Fuzo, Antonio Edson R. Oliveira, Luana Aparecida Rogerio, Nayore Tamie Takamiya, Gabriela Pessenda, Enaldo Vieira de Melo, Angela Maria da Silva, Amélia Ribeiro Jesus, Vanessa Carregaro, Helder I. Nakaya, Roque Pacheco Almeida, and João Santana da Silva
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blood transcriptomics ,human visceral leishmaniasis ,Leishmania infantum (syn. Leishmania chagasi) ,mRNA sequencing (mRNA-seq) ,long noncoding RNA–mRNA coexpression ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Visceral leishmaniasis (VL) is a vector-borne infectious disease that can be potentially fatal if left untreated. In Brazil, it is caused by Leishmania infantum parasites. Blood transcriptomics allows us to assess the molecular mechanisms involved in the immunopathological processes of several clinical conditions, namely, parasitic diseases. Here, we performed mRNA sequencing of peripheral blood from patients with visceral leishmaniasis during the active phase of the disease and six months after successful treatment, when the patients were considered clinically cured. To strengthen the study, the RNA-seq data analysis included two other non-diseased groups composed of healthy uninfected volunteers and asymptomatic individuals. We identified thousands of differentially expressed genes between VL patients and non-diseased groups. Overall, pathway analysis corroborated the importance of signaling involving interferons, chemokines, Toll-like receptors and the neutrophil response. Cellular deconvolution of gene expression profiles was able to discriminate cellular subtypes, highlighting the contribution of plasma cells and NK cells in the course of the disease. Beyond the biological processes involved in the immunopathology of VL revealed by the expression of protein coding genes (PCGs), we observed a significant participation of long noncoding RNAs (lncRNAs) in our blood transcriptome dataset. Genome-wide analysis of lncRNAs expression in VL has never been performed. lncRNAs have been considered key regulators of disease progression, mainly in cancers; however, their pattern regulation may also help to understand the complexity and heterogeneity of host immune responses elicited by L. infantum infections in humans. Among our findings, we identified lncRNAs such as IL21-AS1, MIR4435-2HG and LINC01501 and coexpressed lncRNA/mRNA pairs such as CA3-AS1/CA1, GASAL1/IFNG and LINC01127/IL1R1-IL1R2. Thus, for the first time, we present an integrated analysis of PCGs and lncRNAs by exploring the lncRNA–mRNA coexpression profile of VL to provide insights into the regulatory gene network involved in the development of this inflammatory and infectious disease.
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- 2022
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7. Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity
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Aline Cavalcanti de Queiroz, Gisele Barbosa, Victória Regina Thomaz de Oliveira, Hélio de Mattos Alves, Marina Amaral Alves, Vanessa Carregaro, João Santana da Silva, Eliezer Jesus Barreiro, Magna Suzana Alexandre-Moreira, and Lidia Moreira Lima
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Medicine ,Science - Abstract
Leishmaniasis is a public health issue. It is among the top five parasitic illnesses worldwide and is one of the most neglected diseases. The current treatment disease includes limitations of toxicity, variable efficacy, high costs and inconvenient doses and treatment schedules. LASSBio-1736 was described as antileishmanial drug-candidate to cutaneous leishmaniasis, displaying plasma stability and with no preliminary signals of hepatic or renal toxicity. In this paper, we described the in vitro pharmacokinetic study of LASSBio-1491 (a less lipophilic isostere of LASSBio-1736) and it is in vitro and in vivo leishmanicidal activities. Our results demonstrated that LASSBio-1491 has high permeability, satisfactory aqueous solubility, long plasma and microsomal half-lives and low in vitro systemic clearance, suggesting a pharmacokinetic profile suitable for its use in a single daily dose. The antileishmanial effect of LASSBio-1491 was confirmed in vitro and in vivo. It exhibited no cytotoxic effect to mammalian cells and displayed good in –vivo effect against BALB/c mice infected with Leishmania major LV39 substrain, being 3 times more efficient than glucantime.
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- 2022
8. Parasitic Load Correlates With Left Ventricular Dysfunction in Patients With Chronic Chagas Cardiomyopathy
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Maykon Tavares de Oliveira, André Schmidt, Maria Cláudia da Silva, Eduardo Antônio Donadi, João Santana da Silva, and José Antônio Marin-Neto
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Trypanosoma cruzi ,Chagas disease ,chronic Chagas cardiomyopathy ,left ventricular ejection fraction ,parasite burden ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: Chronic Chagas disease (CChD), one of the infectious parasitic diseases with the greatest social and economic impact upon a large part of the American continent, has distinct clinical manifestations in humans (cardiac, digestive, or mixed clinical forms). The mechanisms underlying the development of the most common and ominous clinical form, the chronic Chagas cardiomyopathy (CCC) have not been completely elucidated, despite the fact that a high intensity of parasite persistence in the myocardium is deemed responsible for an untoward evolution of the disease. The present study aimed to assess the parasite load CCC and its relation to left ventricular ejection fraction (LVEF), a definite prognostic marker in patients with CCC.Methods: Patients with CCC were clinically evaluated using 12-lead-electrocardiogram, echocardiogram, chest X-ray. Peripheral blood sampling (5 ml of venous blood in guanidine/EDTA) was collected from each patient for subsequent DNA extraction and the quantification of the parasite load using real-time PCR.Results: One-hundred and eighty-one patients with CCC were evaluated. A total of 140 (77.3%) had preserved left ventricular ejection fraction (of ≥40%), and 41 individuals had LV dysfunction (LVEF of
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- 2021
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9. Intra-Discrete Typing Unit TcV Genetic Variability of Trypanosoma cruzi in Chronic Chagas' Disease Bolivian Immigrant Patients in Barcelona, Spain
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Maykon Tavares de Oliveira, Elena Sulleiro, Maria Cláudia da Silva, Aroa Silgado, Marta de Lana, João Santana da Silva, Israel Molina, and J. Antônio Marin-Neto
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Chagas disease ,Trypanosoma cruzi ,DTU TcV ,genetic variability ,cardiac form ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background:Trypanosoma cruzi has a high rate of biological and genetic variability, and its population structure is divided into seven distinct genetic groups (TcI-TcVI and Tcbat). Due to immigration, Chagas disease (ChD), caused by T. cruzi, has become a serious global health problem including in Europe. Therefore, the aim of this study was to evaluate the existence of genetic variability within discrete typing unit (DTU) TcV of T. cruzi in Bolivian patients with chronic ChD residing in Barcelona, Spain.Methods: The DNA was extracted from the peripheral blood of 27 patients infected with T. cruzi DTU TcV and the fragments of the genetic material were amplificated through the low stringency single primer-polymerase chain reaction (LSSP-PCR). The data generated after amplification were submitted to bioinformatics analysis.Results: Of the 27 patients evaluated in the study, 8/27 (29.6%) were male and 19/27 (70.4%) female, 17/27 (62.9%) were previously classified with the indeterminate clinical form of Chagas disease and 10/27 (37.1%) with Chagas cardiomyopathy. The LSSP-PCR detected 432 band fragments from 80 to 1,500 bp. The unweighted pair-group method analysis and principal coordinated analysis data demonstrated the existence of three distinct genetic groups with moderate-high rates of intraspecific genetic variability/diversity that had shared parasite's alleles in patients with the indeterminate and cardiomyopathy forms of ChD.Conclusions: This study demonstrated the existence of a moderate to high rate of intra-DTU TcV variability in T. cruzi. Certain alleles of the parasite were associated with the absence of clinical manifestations in patients harboring the indeterminate form of ChD. These results support the need to search for increasingly specific targets in the genome of T. cruzi to be correlated with its main biological properties and clinical features in patients with chronic ChD.
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- 2021
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10. Quantification of parasite burden of Trypanosoma cruzi and identification of Discrete Typing Units (DTUs) in blood samples of Latin American immigrants residing in Barcelona, Spain.
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Maykon Tavares de Oliveira, Elena Sulleiro, Aroa Silgado Gimenez, Marta de Lana, Bianca Zingales, João Santana da Silva, J Antônio Marin-Neto, and Israel Molina
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BACKGROUND:Trypanosoma cruzi has a high genetic and biological diversity and has been subdivided into seven genetic lineages, named TcI-TcVI and TcBat. DTUs TcI-TcII-TcV and TcVI are agents of ChD in different regions of Latin America. Due to population movements, the disease is an emergent global public health problem. Thus, the aim of this study was to quantify the parasitic load and identify the presence of T. cruzi DTUs in 101 Latin American immigrants with chronic ChD, residing in Barcelona, Spain. METHODOLOGY / PRINCIPAL FINDINGS:5ml of peripheral blood were collected in guanidine/EDTA from each patient for DNA extraction, quantification of the parasitic load and genotyping. A great variation of the parasitic load of the patients was verified: from 0.001 to 22.2 T. cruzi DNA (fg) / Blood DNA (ng). In patients from Bolivia the parasitic load was 3.76±4.43 T. cruzi DNA (fg) / Blood DNA (ng) (mean ± SD), in patients of other countries was 0.95±1.38 T. cruzi DNA (fg) / Blood DNA (ng). No statistically significant difference was observed in the parasitic load between patients with the indeterminate and cardiac forms of ChD (p = 0,57). Parasite genotyping was performed by multilocus conventional PCR. In patients from Bolivia there was a nearly equal prevalence of DTUs TcV (27/77), TcII/TcV/TcVI (26/77), and TcII/TcVI (22/77). TcVI was detected in only 2 samples (2/77). A higher prevalence of TcII/TcVI (19/24) was verified in patients of other countries, with low prevalence of TcII/TcV/TcVI (4/24) and TcV (1/24). CONCLUSIONS/SIGNIFICANCE:In this study, low/medium parasitic load was found in all patients evaluated. Our data corroborate previous conclusions indicating that patients from the Bolivia, living in Spain, are predominantly infected by TcV, and TcVI DTUs. On the other hand, in Non-Bolivians patients TcII/TcVI predominated. Surprisingly, in our cohort of 101 patients no infection by TcI DTU was observed.
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- 2020
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11. TLR4 abrogates the Th1 immune response through IRF1 and IFN-β to prevent immunopathology during L. infantum infection.
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Laís Amorim Sacramento, Luciana Benevides, Sandra Regina Maruyama, Lucas Tavares, Kiyoshi Ferreira Fukutani, Marcela Francozo, Tim Sparwasser, Fernando Queiroz Cunha, Roque Pacheco Almeida, João Santana da Silva, and Vanessa Carregaro
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
A striking feature of human visceral leishmaniasis (VL) is chronic inflammation in the spleen and liver, and VL patients present increased production levels of multiple inflammatory mediators, which contribute to tissue damage and disease severity. Here, we combined an experimental model with the transcriptional profile of human VL to demonstrate that the TLR4-IFN-β pathway regulates the chronic inflammatory process and is associated with the asymptomatic form of the disease. Tlr4-deficient mice harbored fewer parasites in their spleen and liver than wild-type mice. TLR4 deficiency enhanced the Th1 immune response against the parasite, which was correlated with an increased activation of dendritic cells (DCs). Gene expression analyses demonstrated that IRF1 and IFN-β were expressed downstream of TLR4 after infection. Accordingly, IRF1- and IFNAR-deficient mice harbored fewer parasites in the target organs than wild-type mice due to having an increased Th1 immune response. However, the absence of TLR4 or IFNAR increased the serum transaminase levels in infected mice, indicating the presence of liver damage in these animals. In addition, IFN-β limits IFN-γ production by acting directly on Th1 cells. Using RNA sequencing analysis of human samples, we demonstrated that the transcriptional signature for the TLR4 and type I IFN (IFN-I) pathways was positively modulated in asymptomatic subjects compared with VL patients and thus provide direct evidence demonstrating that the TLR4-IFN-I pathway is related to the nondevelopment of the disease. In conclusion, our results demonstrate that the TLR4-IRF1 pathway culminates in IFN-β production as a mechanism for dampening the chronic inflammatory process and preventing immunopathology development.
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- 2020
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12. Epigenetic and parasitological parameters are modulated in EBi3-/- mice infected with Schistosoma mansoni.
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Ester Alves Mota, Andressa Barban do Patrocínio, Vanderlei Rodrigues, João Santana da Silva, Vanessa Carregaro Pereira, and Renata Guerra-Sá
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Schistosoma mansoni adaptive success is related to regulation of replication, transcription and translation inside and outside the intermediate and definitive host. We hypothesize that S. mansoni alters its epigenetic state in response to the mammalian host immune system, reprogramming gene expression and altering the number of eggs. In response, a change in the DNA methylation profile of hepatocytes could occurs, modulating the extent of hepatic granuloma. To investigate this hypothesis, we used the EBi3-/- murine (Mus musculus) model of S. mansoni infection and evaluated changes in new and maintenance DNA methylation profiles in the liver after 55 days of infection. We evaluated expression of epigenetic genes and genes linked to histone deubiquitination in male and female S. mansoni worms. Comparing TET expression with DNMT expression indicated that DNA demethylation exceeds methylation in knockout infected and uninfected mice and in wild-type infected and uninfected mice. S. mansoni infection provokes activation of demethylation in EBi3-/-I mice (knockout infected). EBi3-/-C (knockout uninfected) mice present intrinsically higher DNA methylation than WTC (control uninfected) mice. EBi3-/-I mice show decreased hepatic damage considering volume and reduced number of granulomas compared to WTI mice; the absence of IL27 and IL35 pathways decreases the Th1 response resulting in minor liver damage. S. mansoni males and females recovered from EBi3-/-I mice have reduced expression of a deubiquitinating enzyme gene, orthologs of which target histones and affect chromatin state. SmMBD and SmHDAC1 expression levels are downregulated in male and female parasites recovered from EBi3-/-, leading to epigenetic gene downregulation in S. mansoni. Changes to the immunological background thus induce epigenetic changes in hepatic tissues and alterations in S. mansoni gene expression, which attenuate liver symptoms in the acute phase of schistosomiasis.
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- 2020
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13. Interaction between saliva’s adenosine and tick parasitism: effects on feeding and reproduction
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Elen Anatriello, Carlo José Freire Oliveira, Nathália Baptista Oliveira, Andressa Fisch, Cristiane Maria Milanezi, João Santana da Silva, Isabel Kinney Ferreira de Miranda-Santos, and Beatriz Rossetti Ferreira
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Ticks ,Rhipicephalus sanguineus ,Saliva ,Adenosine ,Dendritic cells ,T cells ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background It has recently been demonstrated that saliva from Rhipicephalus sanguineus ticks contains adenosine (ADO) and prostaglandin E2 (PGE2), two non-protein molecules that have significant immunomodulatory properties. These molecules can inhibit cytokine production by dendritic cells (DCs), while also reducing the expression of CD40 in these cells. However, more studies are needed for a better understanding of their participation in the feeding of ticks in vivo. This work, therefore, evaluated the importance of ADO during tick infestations. Mice were infested with adult ticks (3 couples/mouse), and their skin was collected at the tick-infested site (3rd and 7th day), and mRNA for receptors of ADO was quantified by real-time PCR. Results Tick infestation increased by four and two times the expression of the A2b and A3v1 receptors on day 3, respectively, while expression of other ADO receptors was unaltered. In addition, we treated mice (n = 10/group) daily with 8-(p-Sulfophenyl)theophylline, 8-pSPT, 20 mg/kg, i.p.), a non-selective antagonist of ADO receptors, and evaluated the performance of ticks during infestations. Female ticks fed on 8-pSPT-treated mice presented a reduction in their engorgement, weight and hatching rates of egg masses, and survival times of larvae compared to the same parameters presented by ticks in the control group. To investigate if these 8-pSPT-treated mice presented altered immune responses, we performed three tick infestations and collected their lymph node cells to determine the percentages and activation state of DCs and cytokine production by lymphocytes by flow cytometry (Cytometric Bead Array technique, CBA). Our data showed that 8-pSPT-treated mice presented an increase in the percentage of DCs as well as of their stimulatory and co-stimulatory molecules (CD40, CD80 and MHCII). Regarding production of T cell cytokines, we observed a significant increase in the levels of IL-2 and a significant decrease in IL-10, IL-17, TNF-α and IFN-γ cytokines. Conclusions These results suggest that ADO produced by ticks helps them feed and reproduce and that this effect may be due to modulation of host DCs and T cells.
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- 2017
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14. Corrigendum to 'Immunocompetent Mice Model for Dengue Virus Infection'
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Denise Gonçalves, Rafael de Queiroz Prado, Eric Almeida Xavier, Natália Cristina de Oliveira, Paulo Marcos Da Matta Guedes, João Santana da Silva, Luiz Tadeu Moraes Figueiredo, and Victor Hugo Aquino
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Technology ,Medicine ,Science - Published
- 2018
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15. Immune Checkpoints in Leprosy: Immunotherapy As a Feasible Approach to Control Disease Progression
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Hayana Ramos Lima, Thaís Helena Gasparoto, Tatiana Salles de Souza Malaspina, Vinícius Rizzo Marques, Marina Jurado Vicente, Elaine Camarinha Marcos, Fabiana Corvolo Souza, Maria Renata Sales Nogueira, Jaison Antônio Barreto, Gustavo Pompermaier Garlet, João Santana da Silva, Vânia Nieto Brito-de-Souza, and Ana Paula Campanelli
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immunotherapy ,leprosy ,T-regulatory cells ,immune checkpoint blockade ,PD-1:PD-L1 ,cytotoxic T-lymphocyte-associated protein 4 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Leprosy remains a health problem in several countries. Current management of patients with leprosy is complex and requires multidrug therapy. Nonetheless, antibiotic treatment is insufficient to prevent nerve disabilities and control Mycobacterium leprae. Successful infectious disease treatment demands an understanding of the host immune response against a pathogen. Immune-based therapy is an effective treatment option for malignancies and infectious diseases. A promising therapeutic approach to improve the clinical outcome of malignancies is the blockade of immune checkpoints. Immune checkpoints refer to a wide range of inhibitory or regulatory pathways that are critical for maintaining self-tolerance and modulating the immune response. Programmed cell-death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4, and lymphocyte-activation gene-3 are the most important immune checkpoint molecules. Several pathogens, including M. leprae, are supposed to utilize these mechanisms to evade the host immune response. Regulatory T cells and expression of co-inhibitory molecules on lymphocytes induce specific T-cell anergy/exhaustion, leading to disseminated and progressive disease. From this perspective, we outline how the co-inhibitory molecules PD-1, PD-L1, and Th1/Th17 versus Th2/Treg cells are balanced, how antigen-presenting cell maturation acts at different levels to inhibit T cells and modulate the development of leprosy, and how new interventions interfere with leprosy development.
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- 2017
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16. Therapeutic Treatment of Arthritic Mice with 15-Deoxy Δ12,14-Prostaglandin J2 (15d-PGJ2) Ameliorates Disease through the Suppression of Th17 Cells and the Induction of CD4+CD25−FOXP3+ Cells
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Vanessa Carregaro, Marcelo H. Napimoga, Raphael S. Peres, Luciana Benevides, Laís Amorim Sacramento, Larissa G. Pinto, Renata Grespan, Thiago M. Cunha, João Santana da Silva, and Fernando Q. Cunha
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Pathology ,RB1-214 - Abstract
The prostaglandin, 15-deoxy Δ12,14-prostaglandin J2 (15d-PGJ2), is a lipid mediator that plays an important role in the control of chronic inflammatory disease. However, the role of prostanoid in rheumatoid arthritis (RA) is not well determined. We demonstrated the therapeutic effect of 15d-PGJ2 in an experimental model of arthritis. Daily administration of 15d-PGJ2 attenuated the severity of CIA, reducing the clinical score, pain, and edema. 15d-PGJ2 treatment was associated with a marked reduction in joint levels of proinflammatory cytokines. Although the mRNA expression of ROR-γt was profoundly reduced, FOXP3 was enhanced in draining lymph node cells from 15d-PGJ2-treated arthritic mice. The specific and polyclonal CD4+ Th17 cell responses were limited during the addition of prostaglandin to cell culture. Moreover, in vitro 15d-PGJ2 increased the expression of FOXP3, GITR, and CTLA-4 in the CD4+CD25− population, suggesting the induction of Tregs on conventional T cells. Prostanoid addition to CD4+CD25− cells selectively suppressed Th17 differentiation and promoted the enhancement of FOXP3 under polarization conditions. Thus, 15d-PGJ2 ameliorated symptoms of collagen-induced arthritis by regulating Th17 differentiation, concomitant with the induction of Tregs, and, consequently, protected mice from diseases aggravation. Altogether, these results indicate that 15d-PGJ2 may represent a potential therapeutic strategy in RA.
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- 2016
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17. Doxycycline and Benznidazole Reduce the Profile of Th1, Th2, and Th17 Chemokines and Chemokine Receptors in Cardiac Tissue from Chronic Trypanosoma cruzi-Infected Dogs
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Guilherme de Paula Costa, Laís Roquete Lopes, Maria Cláudia da Silva, Aline Luciano Horta, Washington Martins Pontes, Cristiane M. Milanezi, Paulo Marcos da Mata Guedes, Wanderson Geraldo de Lima, Richard Schulz, João Santana da Silva, and Andre Talvani
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Pathology ,RB1-214 - Abstract
Chemokines (CKs) and chemokine receptors (CKR) promote leukocyte recruitment into cardiac tissue infected by the Trypanosoma cruzi. This study investigated the long-term treatment with subantimicrobial doses of doxycycline (Dox) in association, or not, with benznidazole (Bz) on the expression of CK and CKR in cardiac tissue. Thirty mongrel dogs were infected, or not, with the Berenice-78 strain of T. cruzi and grouped according their treatments: (i) two months after infection, Dox (50 mg/kg) 2x/day for 12 months; (ii) nine months after infection, Bz (3,5 mg/kg) 2x/day for 60 days; (iii) Dox + Bz; and (iv) vehicle. After 14 months of infection, hearts were excised and processed for qPCR analysis of Th1 (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL11), Th2 (CCL1, CCL17, CCL24, and CCL26), Th17 (CCL20) CKs, Th1 (CCR5, CCR6, and CXCR3), and Th2/Th17 (CCR3, CCR4, and CCR8) CKR, as well as IL-17. T. cruzi infection increases CCL1, CCL2, CCL4, CCL5, CCL17, CXCL10, and CCR5 expression in the heart. Dox, Bz, or Dox + Bz treatments cause a reversal of CK and CKR and reduce the expression of CCL20, IL-17, CCR6, and CXCR3. Our data reveal an immune modulatory effect of Dox with Bz, during the chronic phase of infection suggesting a promising therapy for cardiac protection.
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- 2016
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18. Histopathological Correlates of Global and Segmental Left Ventricular Systolic Dysfunction in Experimental Chronic Chagas Cardiomyopathy
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Luciano Fonseca Lemos de Oliveira, Minna Moreira Dias Romano, Eduardo Elias Vieira de Carvalho, Jorge Mejia Cabeza, Hélio Cesar Salgado, Rubens Fazan Júnior, Renata Sesti Costa, João Santana da Silva, Maria de Lourdes Higuchi, Benedito Carlos Maciel, Edécio Cunha‐Neto, José Antônio Marin‐Neto, and Marcus Vinícius Simões
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Chagas heart failure ,echocardiography ,pathology ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundChronic Chagas cardiomyopathy in humans is characterized by segmental left ventricular wall motion abnormalities (WMA), mainly in the early stages of disease. This study aimed at investigating the detection of WMA and its correlation with the underlying histopathological changes in a chronic Chagas cardiomyopathy model in hamsters. Methods and ResultsFemale Syrian hamsters (n=34) infected with 3.5×104 or 105 blood trypomastigote Trypanosoma cruzi (Y strain) forms and an uninfected control group (n=7) were investigated. After 6 or 10 months after the infection, the animals were submitted to in vivo evaluation of global and segmental left ventricular systolic function by echocardiography, followed by euthanasia and histological analysis for quantitative assessment of fibrosis and inflammation with tissue sampling in locations coinciding with the left ventricular wall segmentation employed at the in vivo echocardiographic evaluation. Ten of the 34 infected animals (29%) showed reduced left ventricular ejection fraction (
- Published
- 2016
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19. Expression of RANTES, eotaxin-2, ICAM-1, LFA-1 and CCR-3 in chronic rhinosinusitis patients with nasal polyposis Expressão de RANTES, eotaxina-2, ICAM-1, LFA-1 e CCR-3 em pacientes com rinossinusite crônica associada à polipose nasossinusal
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Fransérgio Emílio Cavallari, Fabiana Cardoso Pereira Valera, Aline Jorge Gallego, Rafael Rossell Malinsky, Daniel Salgado Küpper, Cristiane Milanezi, João Santana da Silva, Edwin Tamashiro, and Wilma Terezinha Anselmo-Lima
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Pólipos Nasais ,Quimiocinas ,Molécula 1 de Adesão Intercelular ,Sinusite ,Nasal Polyps ,Chemokines ,Intercellular Adhesion Molecule-1 ,Sinusitis ,Surgery ,RD1-811 - Abstract
PURPOSE: To compare gene expression of the chemokines RANTES and eotaxin-2, its receptor, CCR-3, adhesion molecule ICAM-1 and its receptor LFA-1 in eosinophilic polyps and in control normal nasal mucosa. METHODS: Gene expression was quantified by Real Time PCR in polyps (n=35) and in healthy nasal mucosa (n=15). RESULTS: Eosinophilic polyps showed a higher expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa. CONCLUSION: Eosinophilic polyps present greater expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa.OBJETIVO: Comparar a expressão gênica das quimiocinas RANTES e eotaxina-2, do seu receptor CCR-3, da molécula de adesão ICAM-1 e do seu receptor LFA-1 entre pólipos nasais eosinofílicos (PE) (n=35) e mucosa nasal controle (n=15). MÉTODOS: Quantificou-se a expressão gênica dos mediadores citados pela técnica de PCR em tempo real em PEs e em mucosas de concha média de pacientes sem doenças nasais ou alteração endoscópica. RESULTADOS: Pólipos eosinofílicos apresentam maior expressão de eotaxina-2 e RANTES, mas não de CCR-3, ICAM-1 e LFA-1, quando comparados as mucosas nasais controles. CONCLUSÃO: Pólipos eosinofícios apresentaram maior expressão de eotaxin-2 and RANTES, mas não de CCR-3, ICAM-1 ou LFA-1,comparada à mucosa nasal controle.
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- 2012
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20. In vitro initial immune response against Leishmania amazonensis infection is characterized by an increased production of IL-10 and IL-13
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Zirlane Castelo B. Coêlho, Maria Jania Teixeira, Erika Freitas Mota, Mércia Sindeaux Frutuoso, João Santana da Silva, Aldina Barral, Manoel Barral-Netto, and Margarida Maria L. Pompeu
- Subjects
Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
The initial encounter of Leishmania with its host's immune system is important in the outcome of infection. Previous studies have shown that PBMCs from healthy volunteers (HV) exposed to Leishmania differ in IFN-γ production. We have expanded such observations evaluating the profile and kinetics of cytokines (IFN-γ, IL-12p70, IL-10, IL-13), chemokines (CCL5, CCL3, CCL4, CXCL10), and chemokine receptors (CCR1,CCR5, CXCR3, CCR4) in vitro L. amazonensis-stimulated of HV́s PBMCs. HVs were divided in groups of high (HR) or low (LR) IFN-γ responders. In both groups, HR and LR, after L. amazonensis infection there was a predominance of IL-10 and IL-13 over IFN-γ production, while IL-12 was produced in similar amount. Regarding chemokines, a more striking difference was observed for CCL3 expression that was lower at 12 hours and 48 hours post infection in LR than in HR. Interestingly, a downregulation of CCR5 and a greater expression of CCR4 were found in low IFN-γ responders. These data suggest that early after L. amazonensis infection there is a cytokine milieu dominated by IL-13 and IL-10, and despite of this environment, IFN-γ is produced, supporting the complexity of the response. It is noteworthy that the pattern of immune response is mounted in first hours after Leishmania stimulation, with the definition of the differentiation of Th1 versus Th2 cells. It remains to be determined if such an in vitro difference has an in vivo counterpart in terms of susceptibility to infection. Keywords: Leishmania amazonensis, interleukin-10, interleukin-13
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- 2010
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21. Inflammation Biomarkers of Advanced Disease in Nongingival Tissues of Chronic Periodontitis Patients
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Thiago Alvares da Costa, Marcelo José Barbosa Silva, Polyanna Miranda Alves, Javier Emílio Lazo Chica, Emilio Zorzo Barcelos, Max Antonio Alves Giani, Gustavo Pompermaier Garlet, João Santana da Silva, Virmondes Rodrigues Júnior, Denise Bertulucci Rocha Rodrigues, and Cristina Ribeiro de Barros Cardoso
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Pathology ,RB1-214 - Abstract
Chronic periodontitis is a multifactorial inflammatory disease that affects supporting structures of the teeth. Although the gingival response is largely described, little is known about the immune changes in the alveolar bone and neighboring tissues that could indicate periodontal disease (PD) activity. Then, in this study we identified the ongoing inflammatory changes and novel biomarkers for periodontitis in the tissues directly affected by the destructive disease in PD patients. Samples were collected by osteotomy in 17 control subjects during extraction of third molars and 18 patients with advanced PD, in which alveoloplasty was necessary after extraction of teeth with previous extensive periodontal damage. Patients presented mononuclear cells infiltration in the connective tissue next to the bone and higher fibrosis area, along with increased accumulation of IL-17+ and TRAP+ cells. The levels of TNF-α and MMP-2 mRNA were also elevated compared to controls and a positive and significant correlation was observed between TNF-α and MMP-2 mRNA expression, considering all samples evaluated. In conclusion, nongingival tissues neighboring large periodontal pockets present inflammatory markers that could predict ongoing bone resorption and disease spreading. Therefore, we suggested that the detailed evaluation of these regions could be of great importance to the assessment of disease progression.
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- 2015
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22. Inflammasome activation is critical to the protective immune response during chemically induced squamous cell carcinoma.
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Thais Helena Gasparoto, Carine Ervolino de Oliveira, Luisa Thomazini de Freitas, Claudia Ramos Pinheiro, Juliana Issa Hori, Gustavo Pompermaier Garlet, Karen Angélica Cavassani, Roxana Schillaci, João Santana da Silva, Dario Simões Zamboni, and Ana Paula Campanelli
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Medicine ,Science - Abstract
Chronic inflammation affects most stages of tumorigenesis, including initiation, promotion, malignant differentiation, invasion and metastasis. Inflammasomes have been described as involved with persistent inflammation and are known to exert both pro and antitumour effects. We evaluated the influence of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase (CASP)-1 in the antitumor immune response using a multistage model of squamous cell carcinoma (SCC) development. Absence of ASC and CASP-1 resulted in an earlier incidence and increased number of papilloma. Loss of inflammassome function in mice resulted in decreased presence of natural killer (NK), dendritic (DC), CD4(+), CD8(+) and CD45RB(+) T cells in the tumor lesions as well as in lymph nodes (LN) compared with WT mice. Increased percentage of CD4(+)CD25(+)Foxp3(+) T cells was associated with association with inflammasome loss of function. Moreover, significant differences were also found with neutrophils and macrophage infiltrating the lesions. Myeloperoxidase (MPO), but not elastase (ELA), activity oscillated among the groups during the SCC development. Levels of proinflammatory cytokines IL-1β, IL-18, Tumor Necrosis Factor (TNF)-α and Interferon (IFN)-γ were decreased in the tumor microenvironment in the absence of inflammasome proteins. These observations suggest a link between inflammasome function and SCC tumorigenesis, indicating an important role for inflammasome activation in the control of SCC development.
- Published
- 2014
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23. Macrophage Trafficking as Key Mediator of Adenine-Induced Kidney Injury
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Matheus Correa-Costa, Tárcio Teodoro Braga, Raphael José Ferreira Felizardo, Vinícius Andrade-Oliveira, Katia Regina Perez, Iolanda Midea Cuccovia, Meire Ioshie Hiyane, João Santana da Silva, and Niels Olsen Saraiva Câmara
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Pathology ,RB1-214 - Abstract
Macrophages play a special role in the onset of several diseases, including acute and chronic kidney injuries. In this sense, tubule interstitial nephritis (TIN) represents an underestimated insult, which can be triggered by different stimuli and, in the absence of a proper regulation, can lead to fibrosis deposition. Based on this perception, we evaluated the participation of macrophage recruitment in the development of TIN. Initially, we provided adenine-enriched food to WT and searched for macrophage presence and action in the kidney. Also, a group of animals were depleted of macrophages with the clodronate liposome while receiving adenine-enriched diet. We collected blood and renal tissue from these animals and renal function, inflammation, and fibrosis were evaluated. We observed higher expression of chemokines in the kidneys of adenine-fed mice and a substantial protection when macrophages were depleted. Then, we specifically investigated the role of some key chemokines, CCR5 and CCL3, in this TIN experimental model. Interestingly, CCR5 KO and CCL3 KO animals showed less renal dysfunction and a decreased proinflammatory profile. Furthermore, in those animals, there was less profibrotic signaling. In conclusion, we can suggest that macrophage infiltration is important for the onset of renal injury in the adenine-induced TIN.
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- 2014
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24. Imunocompetent Mice Model for Dengue Virus Infection
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Denise Gonçalves, Rafael de Queiroz Prado, Eric Almeida Xavier, Natália Cristina de Oliveira, Paulo Marcos da Matta Guedes, João Santana da Silva, Luiz Tadeu Moraes Figueiredo, and Victor Hugo Aquino
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Technology ,Medicine ,Science - Abstract
Dengue fever is a noncontagious infectious disease caused by dengue virus (DENV). DENV belongs to the family Flaviviridae, genus Flavivirus, and is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease) in the world. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis. In our study, we have found that immunocompetent C57BL/6 mice infected intraperitoneally with DENV-1 presented some signs of dengue disease such as thrombocytopenia, spleen hemorrhage, liver damage, and increase in production of IFNγ and TNFα cytokines. Moreover, the animals became viremic and the virus was detected in several organs by real-time RT-PCR. Thus, this animal model could be used to study mechanism of dengue virus infection, to test antiviral drugs, as well as to evaluate candidate vaccines.
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- 2012
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25. Dose-response met-RANTES treatment of experimental periodontitis: a narrow edge between the disease severity attenuation and infection control.
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Carlos Eduardo Repeke, Samuel Barros Ferreira, Andreia Espindola Vieira, Elcia Maria Silveira, Mario Julio Avila-Campos, João Santana da Silva, Carlos Ferreira Santos, Ana Paula Campanelli, Ana Paula Favaro Trombone, and Gustavo Pompermaier Garlet
- Subjects
Medicine ,Science - Abstract
Chemokines and chemokine receptors have been implicated in the selective migration of leukocyte subsets to periodontal tissues, which consequently influences the disease outcome. Among these chemoattractants, the chemokines CCL3, CCL4 and CCL5 and its receptors, CCR1 and CCR5, have been associated with increased disease severity in mice and humans. Therefore, in this study we investigated the modulation of experimental periodontitis outcome by the treatment with a specific antagonist of CCR1 and 5 receptors, called met-RANTES. C57Bl/6 mice was orally infected with Aggregatibacter actinomycetemcomitans and treated with 0.05, 0.1, 0.5, 1.5 and 5 mg doses of met-RANTES on alternate days, and evaluated by morphometric, cellular, enzymatic and molecular methods. At 0.5 mg up to 5 mg doses, a strong reduction in the alveolar bone loss and inflammatory cell migration were observed. Interestingly, 5 mg dose treatment resulted in the maximum inhibition of inflammatory cell migration, but resulted in a similar inhibition of bone loss when compared with the lower doses, and also resulted in increased bacterial load and CRP response. When 0.5 and 5 mg therapy regimens were compared it was observed that both therapeutic protocols were able to downregulate the levels of pro-inflammatory, Th1-type and osteoclastogenic cytokines, and CD3+ and F4/80+ cells migration to periodontal tissues, but the high dose modulates host response in a more pronounced and unspecific and excessive way, interfering also with the production of antimicrobial mediators such as MPO, iNOS and IgG, and with GR1+ and CD19+ cells migration. Our results demonstrate a thin line between beneficial immunoregulation and impaired host defense during experimental periodontitis, and the determination of the exact equilibrium point is mandatory for the improvement of immune-targeted therapy of periodontitis.
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- 2011
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26. In vitro initial immune response against Leishmania amazonensis infection is characterized by an increased production of IL-10 and IL-13
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Zirlane Castelo B Coêlho, Maria Jania Teixeira, Erika Freitas Mota, Mércia Sindeaux Frutuoso, João Santana da Silva, Aldina Barral, Manoel Barral-Netto, and Margarida Maria L Pompeu
- Subjects
Leishmania amazonensis ,interleukin-10 ,interleukin-13 ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
The initial encounter of Leishmania with its host's immune system is important in the outcome of infection. Previous studies have shown that PBMCs from healthy volunteers (HV) exposed to Leishmania differ in IFN-γ production. We have expanded such observations evaluating the profile and kinetics of cytokines (IFN-γ, IL-12p70, IL-10, IL-13), chemokines (CCL5, CCL3, CCL4, CXCL10), and chemokine receptors (CCR1,CCR5, CXCR3, CCR4) in vitro L. amazonensis-stimulated of HV's PBMCs. HVs were divided in groups of high (HR) or low (LR) IFN-γ responders. In both groups, HR and LR, after L. amazonensis infection there was a predominance of IL-10 and IL-13 over IFN-γ production, while IL-12 was produced in similar amount. Regarding chemokines, a more striking difference was observed for CCL3 expression that was lower at 12 hours and 48 hours post infection in LR than in HR. Interestingly, a downregulation of CCR5 and a greater expression of CCR4 were found in low IFN-γ responders. These data suggest that early after L. amazonensis infection there is a cytokine milieu dominated by IL-13 and IL-10, and despite of this environment, IFN-γ is produced, supporting the complexity of the response. It is noteworthy that the pattern of immune response is mounted in first hours after Leishmania stimulation, with the definition of the differentiation of Th1 versus Th2 cells. It remains to be determined if such an in vitro difference has an in vivo counterpart in terms of susceptibility to infection
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27. DIMENSIONAMENTO E IMPLANTAÇÃO DE UM SISTEMA OFF GRID EM PORTO RICO - COMUNIDADE DA RESEX TAPAJÓS ARAPIUNS NA AMAZÔNIA
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Dos Santos Sena, Jocienisson, primary, Yúri Campos Lacerda, Gabriel, additional, Kaick da Rocha Sousa, Carlisson, additional, João Santana da Silva, Lázaro, additional, and roberval pimentel santos, manoel, additional
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- 2023
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28. DIMENSIONAMENTO E IMPLANTAÇÃO DE UM SISTEMA OFF GRID EM CACHOEIRINHA DO MENTAE - COMUNIDADE DA RESEX TAPAJÓS ARAPIUNS NA AMAZÔNIA
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Yúri Campos Lacerda, Gabriel, primary, Kaick da Rocha Sousa, Carlisson, additional, Góis Nogueira, Daniela, additional, roberval pimentel santos, manoel, additional, and João Santana da Silva, Lázaro, additional
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- 2023
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29. IMPLANTAÇÃO DE UMA TURBINA HIDROCINÉTICA EM UMA COMUNIDADE DA AMAZÔNIA
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de Almeida Pires Filhos, Valber, primary, roberval pimentel santos, manoel, additional, Eduarda Coimbra Eloi, Maria, additional, and João Santana da Silva, Lázaro, additional
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- 2023
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30. HLA-G, cytokines, and cytokine receptors in the non-aggressive basal cell carcinoma microenvironment
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Eduardo Antônio Donadi, Cacilda da Silva Souza, Edson Garcia Soares, João Santana da Silva, Luiz Gustavo Gardinassi, and Andrezza Telles Westin
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Male ,Skin Neoplasms ,medicine.medical_treatment ,Dermatology ,Human leukocyte antigen ,Biology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Immune system ,HLA-G ,Tumor Microenvironment ,medicine ,Humans ,Basal cell carcinoma ,Receptors, Cytokine ,Receptor ,Aged ,HLA-G Antigens ,General Medicine ,medicine.disease ,Immunohistochemistry ,Interleukin 10 ,Cytokine ,Carcinoma, Basal Cell ,030220 oncology & carcinogenesis ,Cancer research ,Female - Abstract
Non-aggressive basal cell carcinoma (BCC) growth is slow and might be mediated by the immune system. This study analysed the human leukocyte antigen (HLA)-G expression and cytokine profile in non-aggressive BCC subtypes from distinct locations. HLA-G was evaluated via immunohistochemistry and cytokine expression was analysed by a quantitative real-time polymerase chain reaction in 26 primary BCC samples, including nodular BCC (nBCC, n = 16) and superficial BCC (n = 10) from cephalic (ceBCC, n = 12) and non-cephalic (n = 14) locations, and by bioinformatics analysis of public GEO databases. Inflammatory infiltrate was concentrated around the tumour nests. HLA-G-positive inflammatory cells (53.85%) were more abundant than HLA-G-positive tumour cells (21.54%, p
- Published
- 2021
31. Recurrent COVID-19 including evidence of reinfection and enhanced severity in thirty Brazilian healthcare workers
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Karla Freire Rezende, Danilo J.P.G. Rocha, Silvia Ines Sardi, Rejane Hughes Carvalho, João Santana da Silva, Luis G.C. Pacheco, Daniel M. Altmann, João Victor Gomes Santos, Camilla Natália Oliveira Santos, Lucas Sousa Magalhães, Juliana Cardoso Alves, Emília Maria Medeiros de Andrade Belitardo, Marília Marques Aquino, Maria Luiza Doria Almeida, Cliomar Alves dos Santos, Gubio Soares Campos, Rafaela Mota de Jesus, Letícia Adrielle dos Santos, Ianaline Lima Santos, Eric R.G.R. Aguiar, Amélia Ribeiro de Jesus, Pedro Germano de Góis Filho, Rosemary J. Boyton, João Paulo Pereira de Almeida, Douglas Siqueira Santos, Roque P. Almeida, Ana Maria Fantini Silva, and Medical Research Council (MRC)
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0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Health Personnel ,030106 microbiology ,Disease ,Severity of Illness Index ,Microbiology ,Antibodies ,Virus ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Internal medicine ,Severity of illness ,medicine ,Humans ,030212 general & internal medicine ,Letter to the Editor ,Blood type ,First episode ,SARS-CoV-2 ,business.industry ,Case-control study ,COVID-19 ,1103 Clinical Sciences ,Chronic infection ,Infectious Diseases ,Case-Control Studies ,Reinfection ,ÍNDICE DE GRAVIDADE DA DOENÇA ,Female ,Observational study ,business ,Brazil - Abstract
BACKGROUND: There is growing concern about individuals reported to suffer repeat COVID-19 disease episodes, these in a small number of cases characterised as de novo infections with distinct sequences, indicative of insufficient protective immunity even in the short term. METHODS: Observational case series and case-control studies reporting 33 cases of recurrent, symptomatic, qRT-PCR positive COVID-19. Recurrent disease was defined as symptomatic recurrence after symptom-free clinical recovery, with release from isolation >14 days from the beginning of symptoms confirmed by qRT-PCR. The case control study-design compared this group of patients with a control group of 62 patients randomly selected from the same COVID-19 database. RESULTS: Of 33 recurrent COVID-19 patients, 26 were female and 30 were HCW. Mean time to recurrence was 50.5 days which was associated with being a HCW (OR 36.4 (p
- Published
- 2021
32. Dilute acid hydrolysis of wastes of fruits from Amazon for ethanol production
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Livia Melo Carneiro, João Santana da Silva, João Paulo Souza, Érica Siqueira de Souza, Amanda Vasconcelos Farias, Ralyvan Araújo dos Santos, Flavia da Silva Fernandes, and Daiana Rodrigues Torres
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Astrocaryum aculeatum ,020209 energy ,02 engineering and technology ,010501 environmental sciences ,01 natural sciences ,Hydrolysate ,lignocellulosic biomass waste ,Hydrolysis ,chemistry.chemical_compound ,Chemical engineering ,Medical technology ,0202 electrical engineering, electronic engineering, information engineering ,Monosaccharide ,Ethanol fuel ,Food science ,Bactris gasipaes ,R855-855.5 ,0105 earth and related environmental sciences ,chemistry.chemical_classification ,acid hydrolysis optimization ,Ethanol ,biology ,Straw ,biology.organism_classification ,saccharification ,chemistry ,TP155-156 ,bactris gasipaes ,TP248.13-248.65 ,Biotechnology - Abstract
This study carried out the screening of wastes from Amazon plants to produce hydrolysates with a high monosaccharides content for ethanol production. Initially, we hydrolyzed (diluted acid) Amazon wastes (peel from the fruit of Astrocaryum aculeatum Meyer, peel from the fruit of Bactris gasipaes Kunth, straw obtained from endocarp of the fruit of Euterpe oleracea Mart., peel from the fruit of Theobroma grandiflorum Schumann and peel from the root of Manihot esculenta Crant) to obtain hydrolysates with the high content of fermentable sugars. Then, we investigated by 23 factorial design the influence of the factors: a) hydrolysis time (min); b) H2SO4-to-waste ratio (g/g) and c) solid-to-liquid ratio (g/mL) in the variables reducing sugars and furans. The hydrolysis of the peel of the fruit of Bactris gasipaes resulted in the highest concentration of reducing sugars (23.7 g/L). After detoxification and concentration process, the Bactris gasipaes hydrolysate results in 96.7 g/L of reducing sugars largely fermentable (90%) by Saccharomyces cerevisiae PE-2. The experimental design demonstrated that the factors H2SO4-to-waste ratio (g/g) and solid-to-liquid ratio (g/mL) were the most significant affecting the final content of reducing sugars and furans in the hydrolysate of the peel of Bactris gasipaes. Hydrolysis time of 4.4 min, H2SO4-to-waste ratio of 0.63 g/g, and the solid-to-liquid ratio of 0.17 g/mL resulted in the concentration of reducing sugars of 49 g/L. This study shows the potential of peels from the fruit of Bactris gasipaes to produce ethanol.
- Published
- 2021
33. Tremorgenic syndrome in suckling lambs due to poisoning by Ipomoea asarifolia
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J. G. Rocha, João Santana da Silva, José Maria Santos, Joaquim Evêncio Neto, Givaldo B. Silva Filho, J. S. Oliveira, Fabio Alencar Mendonca, Marcela Mota, and H. A. S. Chaves
- Subjects
Traditional medicine ,biology ,Veterinary (miscellaneous) ,Ipomoea asarifolia ,biology.organism_classification - Published
- 2019
34. Expression of B lymphocyte-induced maturation protein 1 (Blimp-1) in keratinocyte and cytokine signalling drives human Th17 response in psoriasis
- Author
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Lorena Carla Oliveira da Costa, Luiz Gustavo Gardinassi, Flávio Protásio Veras, Cristiane Milanezi, Leandra Náira Zambelli Ramalho, Luciana Benevides, José Carlos Alves-Filho, João Santana da Silva, and Cacilda da Silva Souza
- Subjects
Dermatology ,General Medicine - Abstract
Transcriptional factor B lymphocyte-induced maturation protein 1 (Blimp-1) is pivotally implicated in T helper 17 (Th17) cell differentiation. This study investigated expression of the Blimp-1 protein, positive regulatory domain 1 (PRDM1), and cytokine genes in psoriasis (PsO). Affected (AS-PsO) and non-affected skin (nAS-PsO) samples were used to assess gene and protein expressions by reverse transcription-quantitative PCR (RT-qPCR), and immunostaining and confocal microscopy, respectively; the normalised public transcriptomic data permitted differential gene expression analyses. On RT-qPCR, PRDM1 and IL17A transcripts showed higher expression in AS-PsO than in nAS-PsO (n = 34) (p0.001; p0.0001, respectively). Confocal microscopy showed Blimp-1 protein expression in epidermal layer keratinocytes in AS-PsO, but not in nAS-PsO. Bioinformatic analysis of the transcriptomic dataset GSE13355 corroborated the increased PRDM1, signal transducer and activator of transcription 3 (STAT3), IL12B, TNF, IL17A, IL6, IL1B, IL22, and IL10 gene expression in AS-PsO, when compared to normal skin and nAS-PsO (p0.001). PRDM1 expression correlated positively (p0.0001) with that of IL17A (r = 0.7), IL1B (r = 0.67), IL12B (r = 0.6), IL6 (r = 0.59), IL22 (r = 0.53), IL23A (r = 0.47), IL21 (r = 0.47), IL27 (r = 0.34), IL23R (r = 0.32), S100 calcium binding protein A9 (r = 0.63), and lipocalin 2 (r = 0.50), and negatively with that of TGFB1 (r = - 0.28) and RORC (r = - 0.60). Blimp-1 may be critical in the pathogenesis of PsO dysregulation involving the Th17 inflammatory pathway. This knowledge may accelerate the development of new treatments.
- Published
- 2021
35. Neutralizing antibody-independent immunity to SARS-CoV-2 in Syrian hamsters and human ACE-2 transgenic mice immunized with a RBD/Nucleocapsid fusion protein
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João Santana da Silva, Bruno Cassaro, Livia V. de Oliveira, Gregório Guilherme Almeida, Santuza M. R. Teixeira, Jorge Kalil, Rubens Daniel Miserani Magalhães, Ana Paula Fernandes, Lídia Paula Faustino, Patrick Orestes de Azevedo, Otávia Luisa Caballero, Bruna Amanda da Cruz Rattis, Tomas Marçal, Daniel Doro, Andres M. Salazar, Alexandre V. Machado, Ricardo T. Gazzinelli, Flávio Guimarães da Fonseca, E. L. Durigon, Simone G. Ramos, Natália Satchiko Hojo-Souza, Natalia Salazar, Julia Neves Teixeira de Castro, Gabriela Burle-Caldas, Marcílio Jorge Fumagalli, and Marconi Augusto
- Subjects
medicine.anatomical_structure ,Immune system ,biology ,Antigen ,Immunity ,T cell ,biology.protein ,medicine ,Antibody ,Neutralizing antibody ,Virology ,Fusion protein ,Virus - Abstract
The nucleocapsid (N) and the receptor binding domain (RBD) of the Spike (S) proteins elicit robust antibody and T cell responses either in vaccinated or COVID-19 convalescent individuals. We generated a chimeric protein that comprises the sequences of RBD from S and N antigens (SpiN). SpiN was highly immunogenic and elicited a strong IFNγ response from T cells and high levels of antibodies to the inactivated virus, but no neutralizing antibodies (nAb). Importantly, hamsters and the human Angiotensin Convertase Enzyme-2-transgenic mice immunized with SpiN were highly resistant to challenge with the wild type SARS-CoV-2, as indicated by viral load, clinical outcome, lung inflammation and lethality. This protective immunity was dependent of CD4+ T and CD8+ T cells, but not by transfer of antibody of vaccinated mice. Thus, our experiment provides an example T cell-mediated immunity and reinforce the concept that T cell target antigens other that the S protein maybe considered to improve SARS-CoV-2 vaccines, and eventually circumvent the immune scape by variants.
- Published
- 2021
36. Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon
- Author
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Sandra Regina, Maruyama, Carlos Alessandro, Fuzo, Antonio Edson R, Oliveira, Luana Aparecida, Rogerio, Nayore Tamie, Takamiya, Gabriela, Pessenda, Enaldo Vieira, de Melo, Angela Maria, da Silva, Amélia Ribeiro, Jesus, Vanessa, Carregaro, Helder I, Nakaya, Roque Pacheco, Almeida, and João Santana, da Silva
- Subjects
Humans ,Leishmaniasis, Visceral ,RNA, Long Noncoding ,RNA, Messenger ,Leishmania infantum ,Transcriptome ,Leishmaniasis - Abstract
Visceral leishmaniasis (VL) is a vector-borne infectious disease that can be potentially fatal if left untreated. In Brazil, it is caused by
- Published
- 2021
37. Interpretation of the Reflectance Spectra of Lithium (Li) Minerals and Pegmatites: A Case Study for Mineralogical and Lithological Identification in the Fregeneda-Almendra Area
- Author
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Encarnación Roda-Robles, Odile Barres, Mônica Perrotta, Maria dos Anjos Ribeiro, Ana Cláudia Teodoro, Alexandre Lima, Joana Cardoso-Fernandes, Filipa Dias, João Santana da Silva, Jean Cauzid, Faculdade de Ciências, and European Commission
- Subjects
remote sensing ,reflectance spectroscopy ,hyperspectral ,geological exploration ,spectral library ,absorption features ,spectral mineralogy ,pegmatite ,lithium ,010504 meteorology & atmospheric sciences ,Reflectance spectroscopy ,Science ,Library science ,European Social Fund ,010502 geochemistry & geophysics ,Master student ,01 natural sciences ,Reflectivity ,Political science ,General Earth and Planetary Sciences ,Geological exploration ,0105 earth and related environmental sciences - Abstract
Reflectance spectroscopy has been used to identify several deposit types. However, applications concerning lithium (Li)-pegmatites are still scarce. Reflectance spectroscopic studies complemented by microscopic and geochemical studies were employed in the Fregeneda–Almendra (Spain–Portugal) pegmatite field to analyze the spectral behavior of Li-minerals and field lithologies. The spectral similarity of the target class (Li-pegmatites) with other elements was also evaluated. Lepidolite was discriminated from other white micas and the remaining Li-minerals. No diagnostic feature of petalite and spodumene was identified, since their spectral curves are dominated by clays. Their presence was corroborated (by complementary techniques) in petalite relics and completely replaced crystals, although the clay-related absorption depths decrease with Li content. This implies that clays can be used as pathfinders only in areas where argillic alteration is not prevalent. All sampled lithologies present similar water and/or hydroxide features. The overall mineral assemblage is very distinct, with lepidolite, cookeite, and orthoclase exclusively identified in Li-pegmatite (being these minerals crucial targets for Li-pegmatite discrimination in real-life applications), while chlorite and biotite can occur in the remaining lithologies. Satellite data can be used to discriminate Li-pegmatites due to distinct reflectance magnitude and mineral assemblages, higher absorptions depths, and distinct Al–OH wavelength position. The potential use of multi- and hyperspectral data was evaluated; the main limitations and advantages were discussed. These new insights on the spectral behavior of Li-minerals and pegmatites may aid in new Li-pegmatite discoveries around the world. The authors would like to thank the financial support provided by FCT–Fundação para a Ciência e a Tecnologia, I.P., with the ERA-MIN/0001/2017–LIGHTS project and, also, with the 869274—GREENPEG—H2020-SC5-2018-2019-2020 project. This work was also supported by national funds through the FCT project UIDB/04683/2020–ICT (Institute of Earth Sciences). Joana Cardoso-Fernandes and Filipa Dias were financially supported within the compass of their respective Ph.D. theses, ref. SFRH/BD/136108/2018 and ref. 2020.05534.BD, by national funds from MCTES through FCT and co-financed by the European Social Fund (ESF) through POCH–Programa Operacional Capital Humano and NORTE 2020 regional program. The Spanish Ministerio de Ciencia, Innovacion y Universidades (Project RTI2018-094097-B-100, with ERDF funds) and the University of Basque County (UPV/EHU) (grant GIU18/084) also contributed economically. The French National Research Agency (ANR–10–LABX 21–LABEX RESSOURCES 21) partly supported the Master Student personal grant, and the 776804–NEXT–H2020-SC5-2017 project participated in equipment purchasing.
- Published
- 2021
38. Parasitic Load Correlates With Left Ventricular Dysfunction in Patients With Chronic Chagas Cardiomyopathy
- Author
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José Antonio Marin-Neto, João Santana da Silva, Maria Cláudia Moreira da Silva, Maykon Tavares de Oliveira, André Schmidt, and Eduardo Antônio Donadi
- Subjects
Chagas disease ,medicine.medical_specialty ,Trypanosoma cruzi ,Disease ,Cardiovascular Medicine ,Parasite load ,chronic Chagas cardiomyopathy ,Chagas Cardiomyopathy ,Internal medicine ,Parasite hosting ,Medicine ,Diseases of the circulatory (Cardiovascular) system ,In patient ,Original Research ,Ejection fraction ,parasite burden ,business.industry ,left ventricular ejection fraction ,Venous blood ,medicine.disease ,RC666-701 ,Cardiology ,MIOCARDIOPATIA CONGESTIVA ,business ,Cardiology and Cardiovascular Medicine - Abstract
Background: Chronic Chagas disease (CChD), one of the infectious parasitic diseases with the greatest social and economic impact upon a large part of the American continent, has distinct clinical manifestations in humans (cardiac, digestive, or mixed clinical forms). The mechanisms underlying the development of the most common and ominous clinical form, the chronic Chagas cardiomyopathy (CCC) have not been completely elucidated, despite the fact that a high intensity of parasite persistence in the myocardium is deemed responsible for an untoward evolution of the disease. The present study aimed to assess the parasite load CCC and its relation to left ventricular ejection fraction (LVEF), a definite prognostic marker in patients with CCC.Methods: Patients with CCC were clinically evaluated using 12-lead-electrocardiogram, echocardiogram, chest X-ray. Peripheral blood sampling (5 ml of venous blood in guanidine/EDTA) was collected from each patient for subsequent DNA extraction and the quantification of the parasite load using real-time PCR.Results: One-hundred and eighty-one patients with CCC were evaluated. A total of 140 (77.3%) had preserved left ventricular ejection fraction (of ≥40%), and 41 individuals had LV dysfunction (LVEF of Conclusion: The blood parasite load is highly variable and seems to be directly related to the reduction of LVEF, an important prognostic factor in CCC patients.
- Published
- 2021
39. Dendritic cells and regulatory T cells expressing CCR4 provide resistance to coxsackievirus B5-induced pancreatitis
- Author
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Isabel C. Guerra-Gomes, Frederico R. C. Costa, Marcela Francozo, João Santana da Silva, and Renata Sesti-Costa
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0301 basic medicine ,Adoptive cell transfer ,Receptors, CCR4 ,Coxsackievirus Infections ,lcsh:Medicine ,Biology ,Coxsackievirus ,T-Lymphocytes, Regulatory ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cell Movement ,medicine ,CCL17 ,Animals ,lcsh:Science ,Multidisciplinary ,lcsh:R ,Cell migration ,Antimicrobial responses ,Dendritic Cells ,medicine.disease ,biology.organism_classification ,Enterovirus B, Human ,Mice, Inbred C57BL ,Chronic infection ,030104 developmental biology ,Pancreatitis ,Conventional dendritic cells ,Viral infection ,Immunology ,lcsh:Q ,Chemokine CCL17 ,Chemokines ,CD8 ,030215 immunology - Abstract
Type B coxsackieviruses (CVB) are enteroviruses responsible for a common infectious myocarditis and pancreatitis. DCs and regulatory T cells (Tregs) are key players in controlling virus replication and regulating the immune response and tissue damage, respectively. However, the mechanisms underlying cellular migration to target tissues remain unclear. In the present study, we found that CVB5 infection induced CCL17 production and controlled the migration of CCR4+ DCs and CCR4+ Tregs to the pancreatic lymph nodes (pLN). CVB5 infection of CCR4−/− mice reduced the migration of the CD8α+ DC subset and reduced DC activation and production of IFN-β and IL-12. Consequently, CCR4−/− mice presented decreased IFN-γ-producing CD4+ and CD8+ T cells, an increased viral load and more severe pancreatitis. In addition, CCR4−/− mice had impaired Treg accumulation in pLN as well as increased T lymphocyte activation. Adoptive transfer of CCR4+ Tregs but not CCR4− Tregs was able to regulate T lymphocyte activation upon CVB5 infection. The present data reveal a previously unknown role for CCR4 in coordinating immune cell migration to CVB-infected tissues and in controlling subsequent pancreatitis. These new insights may contribute to the design of future therapies for acute and chronic infection of non-polio enteroviruses.
- Published
- 2019
40. Organometallic Gold(III) Complex [Au(Hdamp)(L14)]+ (L1 = SNS-Donating Thiosemicarbazone) as a Candidate to New Formulations against Chagas Disease
- Author
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Fernanda dos Reis Rocho, Zumira A. Carneiro, Ronaldo Junio de Oliveira, José Paulo Aldério Almeida, João Santana da Silva, Sérgio de Albuquerque, Carla D. Lopes, Carlos A. Montanari, Ana P S Gaspari, Bruna Possato, Ulrich Abram, Pedro I. S. Maia, and Andrei Leitão
- Subjects
0301 basic medicine ,Chagas disease ,medicine.medical_specialty ,business.industry ,Public health ,030106 microbiology ,Treatment outcome ,Drug resistance ,Pharmacology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,Infectious Diseases ,Gold iii ,medicine ,business - Abstract
Chagas disease remains a serious public health concern with unsatisfactory treatment outcomes due to strain-specific drug resistance and various side effects. To identify new therapeutic drugs agai...
- Published
- 2019
41. The lack of PI3Kγ favors M1 macrophage polarization and does not prevent kidney diseases progression
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João Santana da Silva, Ivan C. Moura, Angela Castoldi, Marina Brito Silva, Marcela Teatin Latancia, Fernanda Fernandes Terra, Niels Olsen Saraiva Camara, Meire Ioshie Hiyane, Mariana Miyagi, Cristhiane Favero Aguiar, Mariane Tami Amano, Matheus Correa-Costa, Raphael José Ferreira Felizardo, Cristiane Naffah de Souza Breda, Welbert Oliveira Pereira, and Vinicius Andrade-Oliveira
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Immunology ,Macrophage polarization ,Proinflammatory cytokine ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,Animals ,Class Ib Phosphatidylinositol 3-Kinase ,Immunology and Allergy ,Macrophage ,Renal Insufficiency, Chronic ,IMUNOLOGIA ,Inflammation ,Pharmacology ,Kidney ,urogenital system ,business.industry ,Macrophages ,Acute kidney injury ,Cell Polarity ,Acute Kidney Injury ,medicine.disease ,Interleukin-12 ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,030220 oncology & carcinogenesis ,Disease Progression ,Tumor necrosis factor alpha ,business ,Ureteral Obstruction ,Kidney disease - Abstract
Acute kidney injury (AKI) and chronic kidney disease (CKD) are major concerns in worldwide public health, and their pathophysiology involves immune cells activation, being macrophages one of the main players of both processes. It is suggested that metabolic pathways could contribute to macrophage modulation and phosphatidylinositol‑3 kinase (PI3K) pathway was shown to be activated in kidneys subjected to ischemia and reperfusion as well as unilateral ureteral obstruction (UUO). Although PI3K inhibition is mostly associated with anti-inflammatory response, its use in kidney injuries has been shown controversial results, which indicates the need for further studies. Our aim was to unveil the role of PI3Kγ in macrophage polarization and in kidney diseases development. We analyzed bone-marrow macrophages polarization from wild-type (WT) and PI3Kγ knockout (PI3K KO) animals. We observed increased expression of M1 (CD86, CCR7, iNOS, TNF, CXCL9, CXCL10, IL-12 and IL-23) and decreased of M2 (CD206, Arg-1, FIZZ1 and YM1) markers in the lack of PI3Kγ. And this modulation was accompanied by higher levels of inflammatory cytokines in PI3K KO M1 cells. PI3K KO mice had increased M1 in steady state kidneys, and no protection was observed in these mice after acute and chronic kidney insults. On the contrary, they presented higher levels of protein-to-creatinine ratio and Kim-1 expression and increased tubular injury. In conclusion, our findings demonstrated that the lack of PI3Kγ favors M1 macrophages polarization providing an inflammatory-prone environment, which does not prevent kidney diseases progression.
- Published
- 2018
42. Tools for Remote Exploration: A Lithium (Li) Dedicated Spectral Library of the Fregeneda–Almendra Aplite–Pegmatite Field
- Author
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Odile Barres, Jean Cauzid, Ana Cláudia Teodoro, Mônica Perrotta, Joana Cardoso-Fernandes, Encarnación Roda-Robles, Filipa Dias, João Santana da Silva, Alexandre Lima, Maria dos Anjos Ribeiro, and Faculdade de Ciências
- Subjects
Information Systems and Management ,010504 meteorology & atmospheric sciences ,chemistry.chemical_element ,Mineralogy ,pegmatite ,engineering.material ,010502 geochemistry & geophysics ,01 natural sciences ,Spectral line ,remote sensing ,reflectance spectroscopy ,Lepidolite ,Pegmatite ,0105 earth and related environmental sciences ,Mineral ,Sample (graphics) ,lcsh:Z ,lcsh:Bibliography. Library science. Information resources ,Computer Science Applications ,Spodumene ,geological exploration ,chemistry ,lithium ,engineering ,Lithium ,Petalite ,spectrometer ,Geology ,Information Systems - Abstract
The existence of diagnostic features in the visible and infrared regions makes it possible to use reflectance spectra not only to identify mineral assemblages but also for calibration and classification of satellite images, considering lithological and/or mineral mapping. For this purpose, a consistent spectral library with the target spectra of minerals and rocks is needed. Currently, there is big market pressure for raw materials including lithium (Li) that has driven new satellite image applications for Li exploration. However, there are no reference spectra for petalite (a Li mineral) in large, open spectral datasets. In this work, a spectral library was built exclusively dedicated to Li minerals and Li pegmatite exploration through satellite remote sensing. The database includes field and laboratory spectra collected in the Fregeneda–Almendra region (Spain–Portugal) from (i) distinct Li minerals (spodumene, petalite, lepidolite); (ii) several Li pegmatites and other outcropping lithologies to allow satellite-based lithological mapping; (iii) areas previously misclassified as Li pegmatites using machine learning algorithms to allow comparisons between these regions and the target areas. Ancillary data include (i) sample location and coordinates, (ii) sample conditions, (iii) sample color, (iv) type of face measured, (v) equipment used, and for the laboratory spectra, (vi) sample photographs, (vii) continuum removed spectra files, and (viii) statistics on the main absorption features automatically extracted. The potential future uses of this spectral library are reinforced by its major advantages: (i) data is provided in a universal file format; (ii) it allows users to compare field and laboratory spectra; (iii) a large number of complementary data allow the comparison of shape, asymmetry, and depth of the absorption features of the distinct Li minerals. The authors are grateful for the financial support provided by FCT– Fundação para a Ciência e a Tecnologia, I.P., through the ERA-MIN/0001/2017–LIGHTS project and also the 869274–GREENPEG–H2020-SC5-2018-2019-2020 project. The work was also supported by National Funds through the FCT project UIDB/04683/2020–ICT (Institute of Earth Sciences). Joana Cardoso-Fernandes and Filipa Dias are financially supported within the compass of their respective Ph.D. theses, ref. SFRH/BD/136108/2018 and ref. 2020.05534.BD, by national funds from MCTES through FCT, and cofinanced by the European Social Fund (ESF) through POCH—Programa Operacional Capital Humano—and NORTE 2020 regional program. The Spanish Ministerio de Ciencia, Innovacion y Universidades (Project RTI2018-094097-B-100, with ERDF funds) and the University of the Basque Country (UPV/EHU) (grant GIU18/084) also contributed economically. The French National Research Agency (ANR–10–LABX 21–LABEX RESSOURCES 21) partly supported Master Student personal grant and the 776804–NEXT– H2020-SC5-2017 project participated to equipment purchase.
- Published
- 2021
43. Classical multifunctional T cells expression do not vary between patients who had one or more episodes of COVID-19
- Author
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Lucas Sousa Magalhães, Priscila Lima dos Santos Almeida, Camilla Natália Oliveira Santos, Roque Pacheco de Almeida, Juliana Cardoso Alves, Amélia Ribeiro de Jesus, Ricardo L. Louzada da Silva L. Louzada da Silva, Fabrícia Alvisi de Oliveira Mendonça, and João Santana da Silva
- Subjects
Coronavirus disease 2019 (COVID-19) ,Expression (architecture) ,Cancer research ,Biology - Published
- 2021
44. NLRP1 acts as a negative regulator of Th17 cell programming in mice and humans with autoimmune diabetes
- Author
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Maria C Foss-Freitas, Jefferson A. Leite, Jefferson Elias-Oliveira, Rita C. Tostes, Josiane F. Silva, Alessandra Pontillo, Frederico R. C. Costa, Diane M. Rassi, Niels Olsen Saraiva Câmara, Jhefferson Barbosa Guimaraes, João Santana da Silva, and Daniela Carlos
- Subjects
0301 basic medicine ,Male ,endocrine system diseases ,Cellular differentiation ,NLR Proteins ,Biology ,Peripheral blood mononuclear cell ,Pyrin domain ,General Biochemistry, Genetics and Molecular Biology ,Autoimmune Diseases ,Diabetes Mellitus, Experimental ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Downregulation and upregulation ,Mice, Inbred NOD ,medicine ,Animals ,Humans ,STAT3 ,Streptozotocin ,Rats ,030104 developmental biology ,Diabetes Mellitus, Type 1 ,INTERLEUCINAS ,Cancer research ,biology.protein ,Th17 Cells ,Interleukin 17 ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β cells. We show here that the protein NOD-like receptor family pyrin domain containing 1 (NLRP1) has a key role in the pathogenesis of mouse and human T1D. More specifically, downregulation of NLRP1 expression occurs during T helper 17 (Th17) differentiation, alongside greater expression of several molecules related to Th17 cell differentiation in a signal transducers and activators of transcription 3 (STAT3)-dependent pathway. These changes lead to a consequent increase in interleukin 17 (IL-17) production within the pancreas and higher incidence of diabetes in streptozotocin (STZ)-injected mice. Finally, in patients with T1D and a SNP (rs12150220) in NLRP1, there is a robust decrease in IL-17 levels in serum and in memory Th17 cells from peripheral blood mononuclear cells. Our results demonstrate that NLRP1 acts as a negative regulator of the Th17 cell polarization program, making it an interesting target for intervention during the early stages of T1D.
- Published
- 2021
45. Interleukin-6 and the gut microbiota influence melanoma progression in obese mice
- Author
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Fabio Takeo Sato, Amanda Campelo L Melo, Meire Ioshie Hiyane, Niels Olsen Saraiva Camara, João Santana da Silva, Jose Donato, Clarice Silvia Taemi Origassa, Felipe V. Pereira, William T. Festuccia, Filipe M. de Melo, Fernanda Fernandes Terra, Frederick Wasinski, Ronaldo C. Araujo, Marcelli Terumi Miyagi, Luiz Augusto Perandini, Marina Brito Silva, and Íris Arantes de Castro
- Subjects
0301 basic medicine ,Leptin ,Cancer Research ,Medicine (miscellaneous) ,Mice, Obese ,Gut flora ,Diet, High-Fat ,digestive system ,03 medical and health sciences ,Mice ,0302 clinical medicine ,MODELOS ANIMAIS DE DOENÇAS ,Medicine ,Animals ,Interleukin 6 ,neoplasms ,Melanoma ,Obese Mice ,030109 nutrition & dietetics ,Nutrition and Dietetics ,biology ,business.industry ,Interleukin-6 ,Cancer ,medicine.disease ,biology.organism_classification ,Obesity ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,B16f10 melanoma ,business - Abstract
There is a strong correlation between obesity and cancer. Here, we investigated the influence of IL-6 and gut microbiota of obese mice in melanoma development. We first evaluated B16F10 melanoma growth in preclinical models for obesity: mice deficient for leptin
- Published
- 2021
46. E. coli O157:H7 outbreak and hemolytic uremic syndrome in a day care center in Brazil
- Author
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Soraya S. Andrade, S. Almeida, M. E. Rodrigues, João Santana da Silva, I. Silva, V. A. D. Goncalves, R. Assis, D. Rodrigues, K. P. Barbosa, C. Cabral, A. Fialho, M. Bispo, and B. Pribul
- Subjects
Microbiology (medical) ,Pediatrics ,medicine.medical_specialty ,Infectious Diseases ,business.industry ,Day care center ,medicine ,Outbreak ,lcsh:RC109-216 ,General Medicine ,business ,lcsh:Infectious and parasitic diseases - Published
- 2020
47. Clinical and epidemiological aspects of patients infected with SARS-CoV-2 variants: a case-control study
- Author
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Aline Mecenas Santana Albuquerque, João Victor Gomes Santos, Sofia Alves Torres, Camilla Natália Oliveira Santos, Lucas Sousa Magalhães, Cliomar Alves dos Santos, Taise Ferreira Cavalcante, Pedro Germano de Gois Filho, Dalmo Correia Filho, João Santana da Silva, Amélia Ribeiro de Jesus, Enaldo Vieira de Melo, and Roque Pacheco de Almeida
- Subjects
General Earth and Planetary Sciences ,General Environmental Science - Abstract
Objective: To compare the clinical outcomes of patients infected with SARS-CoV-2 variants with patients infected with the original strain. Methods: This is a case control study comparing cases of COVID-19 patients infected with SARS-CoV-2 variants of concern identified by genomic sequencing, with a control group of 62 patients randomly selected from a COVID-19 database of patients diagnosed prior to the emergence of these variants. Findings: In the 40 patients infected with variants, the predominant (52.5%) was P.1 variant. The variant group presented more arthralgia (p=0.015), hyporexia (p=0.006), nausea/vomiting (p=0.048), and mental confusion (p=0.029), the last not identified in the control group. There were no significant differences in comorbidities or demographic data between the groups. Severe disease, according to the WHO Clinical Progression Scale, was identified only in those infected with the variants, as well as high-flow oxygen therapy and ICU admission (p=0.05). The two deaths reported in the study were in patients infected with the variants. Conclusions: The worst outcomes were observed in the group infected with SARS-CoV-2 variants, although no significant differences in comorbidities or demographics date were observed between the groups.
- Published
- 2022
48. Reflectance spectroscopy to validate remote sensing data/algorithms for satellite-based lithium (Li) exploration (Central East Portugal)
- Author
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Jean Cauzid, João Santana da Silva, Mônica Perrotta, Maria dos Anjos Ribeiro, Encarnación Roda-Robles, Ana Cláudia Teodoro, Joana Cardoso-Fernandes, Alexandre Lima, Faculdade de Ciências da Universidade do Porto (FCUP), Universidade do Porto, Brazilian Geological Survey - CPRM, GeoRessources, Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Institut national des sciences de l'Univers (INSU - CNRS), University of Pais Vasco, and Faculdade de Ciências
- Subjects
geology ,Spectral signature ,010504 meteorology & atmospheric sciences ,Lithology ,[SDU.STU.GP]Sciences of the Universe [physics]/Earth Sciences/Geophysics [physics.geo-ph] ,[SDU.STU]Sciences of the Universe [physics]/Earth Sciences ,Image processing ,pegmatite ,Remote sensing ,010502 geochemistry & geophysics ,01 natural sciences ,Spectral line ,Remote sensing (archaeology) ,field validation ,lithium ,spectral library ,False positive paradox ,Calibration ,Satellite ,Algorithm ,Geology ,0105 earth and related environmental sciences - Abstract
International audience; The acquisition of field data plays an important role in the calibration of the remotely sensed data, especially when combined with reflectance spectroscopy studies. The study area of this work is the Fregeneda-Almendra pegmatite field (spreading from Portugal to Spain) where different lithium (Li)-pegmatites are known. Several image processing techniques were applied to satellite images for Li exploration in the region, including machine learning classifiers. However, these algorithms identified several zones as Li-pegmatites false positives. Taking this into account, the following objectives were delineated: (i) validate the training areas used in previous studies and collect field data for training area refinement; (ii) assess the reason for the false positives previously obtained through field surveys. For that, various outcropping lithologies (Li-pegmatite, metasediments, granite) were sampled for laboratory spectral analysis. The spectral signature of Li-pegmatite was compared with the remaining outcropping lithologies. Also, the spectral signature of the sampled false positive areas was confronted with the spectra of Li-minerals. It was possible to conclude that these two classes present similar water/hydroxide and Al-OH-related features. The sampled granitic and metasedimentary rocks also presented water and/or hydroxide absorption features that can lead to some spectral confusion. However, Li-pegmatites can be discriminated from the remaining lithologies either in the training areas and the false positive areas due to the absence of iron-related absorption features and to the distinct reflectance magnitudes.
- Published
- 2020
49. Characterization of lithium (Li) minerals from the Fregeneda-Almendra region through laboratory spectral measurements: a comparative study
- Author
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Mônica Perrotta, João Santana da Silva, Encarnación Roda-Robles, Joana Cardoso-Fernandes, Jean Cauzid, Ana Cláudia Teodoro, Alexandre Lima, Faculdade de Ciências, Faculdade de Ciências da Universidade do Porto (FCUP), Universidade do Porto, Geological Survey of Brazil (CPRM), GeoRessources, Institut national des sciences de l'Univers (INSU - CNRS)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Universidad del Pais Vasco
- Subjects
Spectral signature ,010504 meteorology & atmospheric sciences ,[SDU.STU.GP]Sciences of the Universe [physics]/Earth Sciences/Geophysics [physics.geo-ph] ,[SDU.STU]Sciences of the Universe [physics]/Earth Sciences ,chemistry.chemical_element ,Mineralogy ,pegmatite ,engineering.material ,010502 geochemistry & geophysics ,01 natural sciences ,remote sensing ,Spodumene ,reflectance spectroscopy ,chemistry ,lithium ,Illite ,engineering ,Lithium ,Lepidolite ,Petalite ,Geological exploration ,Clay minerals ,Pegmatite ,Geology ,0105 earth and related environmental sciences - Abstract
International audience; Although several lithium (Li) bearing minerals have already been spectrally characterized, there are no current reference spectra for petalite in large and public access spectral libraries. This fact is aggravated by the difficulty in the identification of petalite's diagnostic features. The study area of this work is the Fregeneda (Spain)-Almendra (Portugal) region, where distinct Li bearing minerals occur in several types of enriched pegmatite dikes. Accordingly, the objectives delineated for this work were: (i) improve the existing knowledge on the spectral signatures of Li bearing minerals (lepidolite, spodumene, petalite); (ii) compare the spectra obtained for petalite and spodumene in the study area; (iii) and compare the spectra of the Li bearing minerals from the Fregeneda-Almendra area with the reference spectra from the United States Geological Survey (USGS), the ECOSTRESS and the Geological Survey of Brazil (CPRM) spectral libraries. For that, spectral measurements were conducted in the laboratory using the SR-6500A (Spectral Evolution, Inc.) spectrometer. The results only allowed to discriminate lepidolite, since that, both, petalite and spodumene, present absorption features typical of montmorillonite and illite, or a combination between these two minerals. This is also verified in samples of corresponding minerals in other spectral libraries. No diagnostic features of these two Li bearing minerals were identified, highlighting the difficulty to spectrally discriminate them from each other and from clay minerals.
- Published
- 2020
50. Polymorphism in the catalytic subunit of the PI3Kγ gene is associated with Trypanosoma cruzi-induced chronic chagasic cardiomyopathy
- Author
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Thiago M. Cunha, Kiyoshi F. Fukutani, Edecio Cunha-Neto, João Santana da Silva, Eduardo Antônio Donadi, Carlos Alessandro Fuzo, Fabrício C. Dias, Maria Cláudia Silva, Felipe Freitas-Castro, and Tiago Medina
- Subjects
0301 basic medicine ,Microbiology (medical) ,Chagas disease ,Chagas Cardiomyopathy ,Genotype ,Trypanosoma cruzi ,030106 microbiology ,Single-nucleotide polymorphism ,Disease ,POLIMORFISMO ,Microbiology ,Asymptomatic ,Polymorphism, Single Nucleotide ,Host-Parasite Interactions ,03 medical and health sciences ,Catalytic Domain ,parasitic diseases ,Genetics ,medicine ,Class Ib Phosphatidylinositol 3-Kinase ,Humans ,Chagas Disease ,Allele ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,PIK3CG ,biology ,Genetic Variation ,Neglected Diseases ,Heart ,medicine.disease ,biology.organism_classification ,030104 developmental biology ,Infectious Diseases ,Immunology ,medicine.symptom ,Signal Transduction - Abstract
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. During the chronic phase of disease, while most infected people do not present symptoms, characterizing the asymptomatic form, some patients develop the cardiac form or chronic chagasic cardiomyopathy, which is considered the most severe manifestation of this disease. Considering that the activation of the PI3Kγ signaling pathway is essential for an efficient immune response against T. cruzi infection, we evaluated the PIK3CG C > T (rs1129293) polymorphism in exon 3 of this gene, which encodes the catalytic subunit of PI3Kγ. The PIK3CG CT and TT genotypes were found to be associated with an increased risk of developing the cardiac form of the disease rather than the asymptomatic or digestive forms. In conclusion, the presence of the T allele at single or double doses may differentiate the cardiac from other clinical manifestations of Chagas disease. This finding should help in further studies to evaluate the mechanisms underlying the differential association of PIK3CG in Chagas disease.
- Published
- 2020
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