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1.
Toxicol In Vitro ; 99: 105873, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38851601

RESUMO

Açaí (Euterpe oleracea MART) is a fruit of great importance for the Amazon region in nutritional, cultural and socioeconomic terms. In recent years, açaí has been the subject of several studies due to its beneficial properties for health, including effects against tumor cells. Therefore, the present work aimed to evaluate in vitro the genotoxic and cytotoxic effects of the clarified extract of açaí juice in a human metastatic gastric cancer cell line (AGP01 cells). For comparison purposes, a non-transformed cell line of African green monkey renal epithelial cells (VERO cells) was used. The viability assay by resazurin reduction, the comet assay, the determination of cell death by differential fluorescent dyes and the wound healing migration assay were performed. A reduction in viability was observed only in the AGP01 line within 72 h. There was no genotoxic damage or cell death (through apoptosis or necrosis) in any of the cell lines. However, açaí extract induced motility reduction in both cell lines. The reduction in cell viability and the induction of the anti-migratory effect in the AGP01 cell line opens perspectives for exploring the potential of açaí as an adjuvant in the treatment of gastric cancer.


Assuntos
Sobrevivência Celular , Dano ao DNA , Euterpe , Extratos Vegetais , Neoplasias Gástricas , Euterpe/química , Sobrevivência Celular/efeitos dos fármacos , Animais , Humanos , Neoplasias Gástricas/tratamento farmacológico , Extratos Vegetais/toxicidade , Extratos Vegetais/farmacologia , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Chlorocebus aethiops , Movimento Celular/efeitos dos fármacos , Ensaio Cometa , Células Vero
2.
Int J Surg Pathol ; 32(1): 119-132, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37150962

RESUMO

Primary effusion lymphoma (PEL) is an aggressive neoplasm often diagnosed in immunosuppressed patients demonstrating peritoneal, pleural, or pericardial effusions. This high-grade lymphoma is strongly associated with human herpesvirus 8 (HHV8) infection and most of the lesions also show the presence of Epstein-Barr virus in tumor cells, which lacks CD20 expression and reveals a plasmablastic morphology and phenotype. The extracavitary or solid variant of PEL is even rarer and usually affects the lymph nodes and is currently considered a clinical manifestation of the classic PEL. In the oral cavity, extracavitary PEL is extremely rare and only a few patients have been previously reported, with no detailed clinicopathological description. The recognition of oral extracavitary PEL is even more important given the occurrence of plasmablastic lymphoma in the oral mucosa, which shares many clinical, microscopic, and phenotypic features with PEL, therefore, demanding from pathologists the search for HHV8, especially in immunosuppressed patients, and an appropriate clinical evaluation. In this report, we aim to describe a very rare extracavitary PEL affecting the palate of a 36-year-old patient and to review the literature regarding the extracavitary presentation of this aggressive lymphoma. This report demonstrates the importance of searching for HHV8 infection in oral lymphomas with plasmablastic features.


Assuntos
Infecções por Vírus Epstein-Barr , Infecções por Herpesviridae , Linfoma de Efusão Primária , Linfoma , Humanos , Adulto , Linfoma de Efusão Primária/patologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4 , Boca/patologia
3.
Pharmaceutics ; 15(9)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37765273

RESUMO

Gastric cancer (GC) is a highly heterogeneous, complex disease and the fifth most common cancer worldwide (about 1 million cases and 784,000 deaths worldwide in 2018). GC has a poor prognosis (the 5-year survival rate is less than 20%), but there is an effort to find genes highly expressed during tumor establishment and use the related proteins as targets to find new anticancer molecules. Data were collected from the Gene Expression Omnibus (GEO) bank to obtain three dataset matrices analyzing gastric tumor tissue versus normal gastric tissue and involving microarray analysis performed using the GPL570 platform and different sources. The data were analyzed using the GEPIA tool for differential expression and KMPlot for survival analysis. For more robustness, GC data from the TCGA database were used to corroborate the analysis of data from GEO. The genes found in in silico analysis in both GEO and TCGA were confirmed in several lines of GC cells by RT-qPCR. The AlphaFold Protein Structure Database was used to find the corresponding proteins. Then, a structure-based virtual screening was performed to find molecules, and docking analysis was performed using the DockThor server. Our in silico and RT-qPCR analysis results confirmed the high expression of the AJUBA, CD80 and NOLC1 genes in GC lines. Thus, the corresponding proteins were used in SBVS analysis. There were three molecules, one molecule for each target, MCULE-2386589557-0-6, MCULE-9178344200-0-1 and MCULE-5881513100-0-29. All molecules had favorable pharmacokinetic, pharmacodynamic and toxicological properties. Molecular docking analysis revealed that the molecules interact with proteins in critical sites for their activity. Using a virtual screening approach, a molecular docking study was performed for proteins encoded by genes that play important roles in cellular functions for carcinogenesis. Combining a systematic collection of public microarray data with a comparative meta-profiling, RT-qPCR, SBVS and molecular docking analysis provided a suitable approach for finding genes involved in GC and working with the corresponding proteins to search for new molecules with anticancer properties.

5.
Genes (Basel) ; 14(2)2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36833388

RESUMO

Non-small cell lung cancer (NSCLC) accounts for the vast majority of cases of lung neoplasms. It is formed in multiple stages, with interactions between environmental risk factors and individual genetic susceptibility and with genes involved in the immune and inflammatory response paths, cell or genome stability, and metabolism, among others. Our objective was to evaluate the association between five genetic variants (IL-1A, NFKB1, PAR1, TP53, and UCP2) and the development of NSCLC in the Brazilian Amazon. The study included 263 individuals with and without lung cancer. The samples were analyzed for the genetic variants of NFKB1 (rs28362491), PAR1 (rs11267092), TP53 (rs17878362), IL-1A (rs3783553), and UCP2 (INDEL 45-bp), which were genotyped in PCR, followed by an analysis of the fragments, in which we applied a previously developed set of informative ancestral markers. We used a logistic regression model to identify differences in the allele and the genotypic frequencies among individuals and their association with NSCLC. The variables of gender, age, and smoking were controlled in the multivariate analysis to prevent confusion by association. The individuals that were homozygous for the Del/Del of polymorphism NFKB1 (rs28362491) (p = 0.018; OR = 0.332) demonstrate a significant association with NSCLC, which was similar to that observed in the variants of PAR1 (rs11267092) (p = 0.023; OR = 0.471) and TP53 (rs17878362) (p = 0.041; OR = 0.510). Moreover, the individuals with the Ins/Ins genotype of polymorphism IL-1A (rs3783553) demonstrated greater risk for NSCLC (p = 0.033; OR = 2.002), as did the volunteers with the Del/Del of UCP2 (INDEL 45-bp) (p = 0.031; OR = 2.031). The five polymorphisms investigated can contribute towards NSCLC susceptibility in the population of the Brazilian Amazon.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Subunidade p50 de NF-kappa B , Receptor PAR-1 , Proteína Supressora de Tumor p53 , Proteína Desacopladora 2 , Humanos , Brasil/epidemiologia , Subunidade p50 de NF-kappa B/genética , Polimorfismo Genético , Receptor PAR-1/genética , Proteína Supressora de Tumor p53/genética
6.
Oncotarget ; 14: 23-39, 2023 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-36634224

RESUMO

The oral mucositis is a mucosal alteration that usually arises from oncological treatments, such as chemotherapy, and it is characterized as an inflammatory process. The aim of this study is to demonstrate the chromatographic constitution of Andiroba oil, comparing and evaluating Andiroba oil and laser scarring efficiency in treatments of oral mucositis in hamsters. These animals were submitted to 5-Fluorouracil. A total of 122 animals were used, randomized and divided into the following groups: (a) positive control; (b) laser associated to andiroba oil; (c) laser; (d) andiroba oil; (e) negative control; (f) cyclophosphamide (genotoxicity control). The induction of oral mucositis occurred by the administration of intraperitoneal Fluorouracila (60 mg/kg) and trauma to the mucosa. The laser protocol was performed once a day and the andiroba oil applied 3 times a day (1,5 ml/day). The mucosae were photographed and removed for clinical and histopathological analysis on day 4, 8, 12 and 15. The analysis was based in OM severity, in specific scoring for the clinical and histopathological aspect. Toxicity was evaluated on day 15 using comet assay and it was performed by variant DNA damage parameters. The data were analysed using analysis of variance (ANOVA) Tukey post-test and Kruskal-Wallis Dunn post-test. The "andiroba oil" and "laser" groups presented better results when compared to the control groups and the treatment associations. The andiroba oil presented the best scarring results, even considering its efficiency proximity to the laser treatment. Andiroba and laser, separately, did not present genotoxicity, however their association evidences damage to DNA.


Assuntos
Terapia com Luz de Baixa Intensidade , Estomatite , Animais , Cricetinae , Cicatriz , Fluoruracila/toxicidade , Terapia com Luz de Baixa Intensidade/métodos , Mesocricetus , Estomatite/induzido quimicamente
7.
Genes (Basel) ; 13(4)2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35456416

RESUMO

In Brazil, Acute lymphoid leukemia (ALL) is the leading cause of cancer deaths in children and adolescents. Treatment toxicity is one of the reasons for stopping chemotherapy. Amerindian genomic ancestry is an important factor for this event due to fluctuations in frequencies of genetic variants, as in the NUDT15 and SLC22A1 genes, which make up the pharmacokinetic and pharmacodynamic pathways of chemotherapy. This study aimed to investigate possible associations between NUDT15 (rs1272632214) and SLC22A1 (rs202220802) gene polymorphism and genomic ancestry as a risk of treatment toxicities in patients with childhood ALL in the Amazon region of Brazil. The studied population consisted of 51 patients with a recent diagnosis of ALL when experiencing induction therapy relative to the BFM 2009 protocol. Our results evidenced a significant association of risk of severe infectious toxicity for the variant of the SLC22A1 gene (OR: 3.18, p = 0.031). Genetic ancestry analyses demonstrated that patients who had a high contribution of African ancestry had a significant protective effect for the development of toxicity (OR: 0.174; p = 0.010), possibly due to risk effects of the Amerindian contribution. Our results indicate that mixed populations with a high degree of African ancestry have a lower risk of developing general toxicity during induction therapy for ALL. In addition, individuals with the SLC22A1 variant have a higher risk of developing severe infectious toxicity while undergoing the same therapy.


Assuntos
Transportador 1 de Cátions Orgânicos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , População Negra , Criança , Humanos , Transportador 1 de Cátions Orgânicos/genética , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pirofosfatases/genética
8.
Genes (Basel) ; 13(3)2022 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-35328047

RESUMO

Lung cancer is one of the most frequent neoplasms in the world. Because it is a complex disease, its formation occurs in several stages, stemming from interactions between environmental risk factors, such as smoking, and individual genetic susceptibility. Our objective was to investigate associations between a UGT1A1 gene polymorphism (rs8175347) and lung cancer risk in an Amazonian population. This is a pilot study, case-controlled study, which included 276 individuals with cancer and without cancer. The samples were analyzed for polymorphisms of the UGT1A1 gene (rs8175347) and genotyped in PCR, followed by fragment analysis in which we applied a previously developed set of informative ancestral markers. We used logistic regression to identify differences in allelic and genotypic frequencies between individuals. Individuals with the TA7 allele have an increased chance of developing lung adenocarcinoma (p = 0.035; OR: 2.57), as well as those with related genotypes of reduced or low enzymatic activity: TA6/7, TA5/7, and TA7/7 (p = 0.048; OR: 8.41). Individuals with homozygous TA7/7 have an increased chance of developing squamous cell carcinoma of the lung (p = 0.015; OR: 4.08). Polymorphism in the UGT1A1 gene (rs8175347) may contribute as a risk factor for adenocarcinoma and lung squamous cell carcinoma in the population of the Amazon region.


Assuntos
Carcinoma de Células Escamosas , Glucuronosiltransferase , Neoplasias Pulmonares , Glucuronosiltransferase/genética , Humanos , Neoplasias Pulmonares/genética , Projetos Piloto , Polimorfismo Genético , Fatores de Risco
9.
Genes (Basel) ; 13(2)2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35205412

RESUMO

Autism spectrum disorder is a neurodevelopmental disorder, affecting one in 160 children worldwide. The causes of autism are still poorly understood, but research shows the relevance of genetic factors in its pathophysiology, including the CHD8, SCN2A, FOXP1 and SYNGAP1 genes. Information about the genetic influence on various diseases, including autism, in the Amerindian population from Amazon, is still scarce. We investigated 35 variants of the CHD8, SCN2A, FOXP1, and SYNGAP1 gene in Amazonian Amerindians in comparison with publicly available population frequencies from the 1000 Genomes Project database. Our study identified 16 variants in the Amerindian population of the Amazon with frequencies significantly different from the other populations. Among them, the SCN2A (rs17183814, rs75109281, and rs150453735), FOXP1 (rs56850311 and rs939845), and SYNGAP1 (rs9394145 and rs115441992) variants presented higher frequency than all other populations analyzed. In addition, nine variants were found with lower frequency among the Amerindians: CHD8 (rs35057134 and rs10467770), SCN2A (rs3769951, rs2304014, rs1838846, and rs7593568), FOXP1 (rs112773801 and rs56850311), and SYNGAP1 (rs453590). These data show the unique genetic profile of the indigenous population of the Brazilian Amazon. Knowledge of these variants can help to understand the pathophysiology and diagnosis of autism among Amerindians, Brazilians, and in admixed populations that have contributions from this ethnic group.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Transtorno do Espectro Autista/genética , Transtorno Autístico/genética , Criança , Exoma , Fatores de Transcrição Forkhead/genética , Frequência do Gene , Humanos , Proteínas Repressoras/genética , Fatores de Transcrição/genética
10.
Genes (Basel) ; 14(1)2022 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-36672804

RESUMO

Gastric cancer (GC) is a multifactorial, complex, and aggressive disease with a prevalence of one million new cases and high global mortality. Factors such as genetic, epigenetic, and environmental changes contribute to the onset and progression of the disease. Identification of INDELs in miRNA and its target sites in current studies showed an important role in the development of cancer. In GC, miRNAs act as oncogenes or tumor suppressors, favoring important cancer pathways, such as cell proliferation and migration. This work aims to investigate INDELs in the coding region of miRNAs (hsa-miR-302c, hsa-miR-548AJ-2, hsa-miR-4274, hsa-miR-630, hsa-miR-516B-2, hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920, has-mir-3171, and hsa-miR-3652) that may be associated with susceptibility and clinical variants of gastric cancer. For this study, 301 patients with GC and 145 individuals from the control group were selected from an admixed population in the Brazilian Amazon. The results showed the hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920 and hsa-miR-3652 variants were associated with gastric cancer susceptibility. The hsa-miR-4463 was significantly associated with clinical features of GC such as diffuse gastric tumor histological type, "non-cardia" localization region, and early onset. Our findings indicated that INDELs could be potentially functional genetic variants for gastric cancer risk.


Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Oncogenes , Biomarcadores Tumorais/genética
11.
Life Sci ; 285: 119949, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34543640

RESUMO

AIMS: Swietenia macrophylla have been considered for the treatment of various diseases, including anticancer activity. This study aimed to investigate the anticancer activity of S. macrophylla leaves extract and its isolated compound towards human colorectal cancer cell line. MAIN METHODS: Hexanic extract of S. macrophylla leaves demonstrated relevant cytotoxicity only against colon cancer cell line HCT116. KEY FINDINGS: Our results showed significant DNA damage and apoptosis after treatment with the hexanic extract of S. macrophylla. Moreover, no toxicity was noticed for the animal model. The isolated compound limonoid L1 showed potent cytotoxicity against cancer cell lines with IC50 at 55.87 µg mL-1. Limonoid L1 did not trigger any cell membrane rupture in the mice erythrocytes suggesting no toxicity. The antiproliferative effect of L1 was confirmed in colorectal cancer cells by clonogenic assay, inducing G2/M arrest, apoptosis, and DNA damage in cancer-type cells. SIGNIFICANCE: L1 reduced BCL2 and increased ATM, CHK2, TP53, ARF, CDK1, CDKN1A, and CASP3 in the colorectal cancer cell line. These findings suggest that limonoid L1 isolated from S. macrophylla can be a promising anticancer agent in managing colorectal cancer.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Colorretais/patologia , Dano ao DNA , Limoninas/farmacologia , Meliaceae/química , Animais , Neoplasias Colorretais/metabolismo , Eritrócitos/efeitos dos fármacos , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Células HCT116 , Hemólise , Humanos , Limoninas/isolamento & purificação , Limoninas/uso terapêutico , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia
12.
In Vivo ; 35(5): 2661-2667, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410954

RESUMO

BACKGROUND/AIM: Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disease, and a major challenge for the eradication of CML is to understand the cause of the permanence of minimal residual disease (DRM). This work aimed to induce the maturation of leukemic stem cells with All-trans-retinoic acid (ATRA), making them sensitive to treatment with Imatinib (IM). MATERIALS AND METHODS: K562 cells were treated with IM and with the combined therapy of ATRA together with IM for 48 and 72 h. The expression of BCR-ABL gene and multidrug resistance gene ABCB1 were evaluated using RT-qPCR. RESULTS: The combined ATRA and IM therapy showed a discreet cell differentiation pattern, evidenced by the panoptic morphology analysis at 48 and 72 h of treatment. The BCR-ABL expression showed no statistical difference when treated alone with IM, however in combination with ATRA, the expression was statistically significant in 48 and 72 h (p≤0.0001) and when the treatment groups were compared to each other (p≤0.001). The ABCB1 gene expression showed a decrease in isolated IM therapy (p≤0.05) and in the combination in 48 and 72 h (p≤0.0001). CONCLUSION: Combined ATRA and IM therapy was shown to be effective in decreasing BCR-ABL and ABCB1 genes, possibly through the differentiation of blast cells, demonstrating that the therapy could be potentially effective in the blast crisis of the disease and for those patients who develop resistance to available CML treatments.


Assuntos
Benzamidas , Leucemia Mielogênica Crônica BCR-ABL Positiva , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Apoptose , Diferenciação Celular , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Piperazinas , Pirimidinas/farmacologia , Tretinoína
13.
Pathogens ; 10(7)2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34357990

RESUMO

Reporter virus neutralization test (RVNT) has been used as an alternative to the more laborious and time-demanding conventional PRNT assay for both DENV and ZIKV. However, few studies have investigated how these techniques would perform in epidemic areas with the circulation of multiple flavivirus. Here, we evaluate the performance of ZIKV and DENV Rluc RVNT and ZIKV mCh RVNT assays in comparison to the conventional PRNT assay against patient sera collected before and during ZIKV outbreak in Brazil. These samples were categorized into groups based on (1) acute and convalescent samples according to the time of disease, and (2) laboratorial diagnostic results (DENV and ZIKV RT-PCR and IgM-capture ELISA). Our results showed that DENV Rluc assay presented 100% and 78.3% sensitivity and specificity, respectively, with 93.3% accuracy, a similar performance to the traditional PRNT. ZIKV RVNT90, on the other hand, showed much better ZIKV antibody detection performance (around nine-fold higher) when compared to PRNT, with 88% clinical sensitivity. Specificity values were on average 76.8%. Even with these results, however, ZIKV RVNT90 alone was not able to reach a final diagnostic conclusion for secondary infection in human samples due to flavivirus cross reaction. As such, in regions where the flavivirus differential diagnosis represents a challenge, we suggest the establishment of a RVNT panel including other flaviviruses circulating in the region, associated with the other serological techniques such as IgM ELISA and the investigation of seroconversion, in order to help define an accurate diagnostic conclusion using serology.

14.
Naunyn Schmiedebergs Arch Pharmacol ; 394(7): 1529-1535, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33755738

RESUMO

Dipyrone or metamizole is one of the most used analgesics, mainly due to its low financial cost. However, in some countries, the sale of dipyrone is prohibited due to reported severe cases of agranulocytosis as a result of its use. Despite its high use, studies showing genotoxic and cytotoxic effects of dipyrone in mammalian cells are scarce. Therefore, in the present study, we assessed cell viability, genotoxic effects, cytotoxic effects (by apoptosis and necrosis induction), and the induction of reactive oxygen species (ROS) in Vero cells (a cell line obtained from the red kidney of green monkey) exposed to dipyrone. Our results showed a significant reduction in viability of cells exposed to dipyrone by the MTT assay. A significant increase in damage index evaluated by a comet assay was also observed, which indicates its genotoxic effects. In which concerns the cytotoxic effects of dipyrone, we observed a significant increase in the number of apoptotic cells using fluorescent dyes after 24 h and 48 h of treatment with the drug. Our results also showed that there was no significant difference in the induction of ROS generation after treatment of the cells with the drug assessed by the DCFH-DA assay. Thus, our work showed that dipyrone is both a genotoxic and cytotoxic drug to Vero cells in the assessed conditions.


Assuntos
Apoptose/efeitos dos fármacos , Citotoxinas/toxicidade , Dano ao DNA/efeitos dos fármacos , Dipirona/toxicidade , Animais , Apoptose/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Chlorocebus aethiops , Dano ao DNA/fisiologia , Relação Dose-Resposta a Droga , Espécies Reativas de Oxigênio/metabolismo , Células Vero
15.
Emerg Microbes Infect ; 9(1): 1023-1033, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32419649

RESUMO

The Asian lineage of Zika virus (ZIKV) is responsible for the recent epidemics in the Americas and severe disease, whereas the African lineage of ZIKV has not been reported to cause epidemics or severe disease. We constructed a cDNA infectious clone (IC) of an African ZIKV strain, which, together with our previously developed Asian ZIKV strain IC, allowed us to engineer chimeric viruses by swapping the structural and non-structural genes between the two lineages. Recombinant parental and chimeric viruses were analyzed in A129 and newborn CD1 mouse models. In the A129 mice, the African strain developed higher viremia, organ viral loading, and mortality rate. In CD1 mice, the African strain exhibited a higher neurovirulence than the Asian strain. A chimeric virus containing the structural genes from the African strain is more virulent than the Asian strain, whereas a chimeric virus containing the non-structural genes from the African strain exhibited a virulence comparable to the Asian strain. These results suggest that (i) African strain is more virulent than Asian strain and (ii) viral structural genes primarily determine the virulence difference between the two lineages in mouse models. Other factors may contribute to the discrepancy between the mouse and epidemic results.


Assuntos
Genes Virais , Variação Genética , Virulência/genética , Infecção por Zika virus/patologia , Zika virus , África , América/epidemiologia , Animais , Ásia , Chlorocebus aethiops , Modelos Animais de Doenças , Humanos , Camundongos , Células Vero , Zika virus/genética , Zika virus/isolamento & purificação , Zika virus/patogenicidade
16.
Funct Plant Biol ; 47(5): 464-472, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32209206

RESUMO

Nitrate (NO3-) fertilisers are commonly used to improve the yield and quality of most non-legume crops such as potato (Solanum tuberosum L.). Root cells absorb nitrate from the soil using plasma membrane-bound transporters. In this study, we overexpressed a putative nitrate transporter from potato (StNPF1.11) to study its effect on the level of tuber protein content in potato. At 10 weeks after planting, overexpression of StNPF1.11 increased the mean level of protein content of all n = 23 transformants by 42% compared with the wild-type control. The level of chlorophyll content in leaves (from upper and lower plant parts) also increased for several individuals at 10 weeks. Tuber yield (fresh) was not structurally impaired; however, the mean tuber dry matter content of the transformants was reduced by 3-8% at 19 weeks. At 19 weeks, an overall increase in protein content was not clearly observed. Throughout plant development, half of the transformants were taller than the control. A basic understanding of the mechanisms that regulate plant nitrogen uptake, transport and utilisation, enable the development of tools to improve both crop nutrition and crop quality that are needed to enhance the viability and sustainability of future plant production systems.


Assuntos
Solanum tuberosum , Proteínas de Transporte de Ânions , Clorofila , Transportadores de Nitrato , Folhas de Planta , Tubérculos , Solanum tuberosum/genética
17.
Med Biol Eng Comput ; 58(3): 519-528, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31900818

RESUMO

Early diagnosis and treatment are the most important strategies to prevent deaths from several diseases. In this regard, data mining and machine learning techniques have been useful tools to help minimize errors and to provide useful information for diagnosis. Our paper aims to present a new feature selection algorithm. In order to validate our study, we used eight benchmark data sets which are commonly used among researchers who developed machine learning methods for medical data classification. The experiment has shown that the performance of our proposed new feature selection method combined with twin-bounded support vector machine (FSTBSVM) is very efficient. The robustness of the FSTBSVM is examined using classification accuracy, analysis of sensitivity, and specificity. The proposed FSTBSVM is a very promising technique for classification, and the results show that the proposed method is capable of producing good results with fewer features than the original data sets. Graphical abstract Model using a new feature selection and grid search with 10-fold CV to optimize model parameters in our FSTBSVM.


Assuntos
Máquina de Vetores de Suporte , Bases de Dados como Assunto , Feminino , Humanos , Redes Neurais de Computação
18.
Food Chem ; 302: 125340, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419775

RESUMO

In this study, 83 wines representating four commercial categories: "Argentinean Malbec", "Brazilian Merlot", "Uruguayan Tannat" and "Chilean Carménère" were analyzed according to their phenolic and volatile compounds. The objective was to identify the chemical compounds that would typify each category. From approximately about 600 peaks obtained by chromatographic techniques, 169 were identified and 53 of them were selected for multivariate statistical analysis. Chilean Carménère was the best discriminated group by the methods applied in our study, followed by Argentinean Malbec. Brazilian Merlot mixed mainly with some Carménère, whileTannat mixed with all wines categories, especially Malbec. In general, Chilean Carménère wines can be characterized by a bluish color, higher amounts of sulphur dioxide, higher content of octanoic acid, isobutanol, ethyl isoamyl succinate and catechin and a smaller amount of quercetin. These data can contribute for further process of authenticity or typification of South American red wines.


Assuntos
Análise de Alimentos/estatística & dados numéricos , Fenóis/análise , Compostos Orgânicos Voláteis/análise , Vinho/análise , Butanóis/análise , Caprilatos/análise , Catequina/análise , Análise de Alimentos/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Cromatografia Gasosa-Espectrometria de Massas/estatística & dados numéricos , Análise Multivariada , Quercetina/análise , América do Sul , Dióxido de Enxofre/análise , Vinho/classificação
19.
J Appl Toxicol ; 39(10): 1405-1412, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31274207

RESUMO

Artesunate (ARS) is a semi-synthetic derivative of artemisinin, used as an outstanding antimalarial drug, which also displays antitumor, anti-inflammatory and immunosuppressive effects. In spite of the numerous reports showing the antitumor activity of ARS, the particular mechanisms associated with its cytotoxicity and genotoxicity in non-neoplastic human cells remain unclear. Here we aimed to verify the specific chromosome damages and the changes in markers of oxidative-nitrosative stress and apoptosis triggered by ARS exposure in human peripheral blood lymphocytes. Cultures were incubated in the presence of ARS and the number of binucleated cells was determined. To discriminate between micronuclei (MN) containing a whole chromosome or an acentric chromosome, the MN test was employed in combination with the fluorescence in situ hybridization assay. Alterations in the levels of superoxide anion (O2- ) and nitric oxide (NO) were measured by the nitroblue tetrazolium and Griess assay, respectively. Changes in the expression of the apoptotic markers were assessed by immunocytochemistry. We found that ARS induced a significant formation of both centromere-positive MN (C+ MN) and centromere-negative MN (C- MN). These alterations were accompanied by an increase in both cellular levels of O2- and total NO production, and a remarkable enhancement in the expression of the apoptotic markers cytochrome c and caspases 8 and 9. Together these findings reveal that ARS induces changes in the oxidative-nitrosative status of human lymphocytes, which are followed by apoptosis and clastogenic and aneugenic effects.


Assuntos
Aneugênicos/efeitos adversos , Artesunato/efeitos adversos , Dano ao DNA/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Mutagênicos/efeitos adversos , Estresse Nitrosativo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
20.
Can J Gastroenterol Hepatol ; 2018: 5804376, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30410872

RESUMO

MYC is an oncogene responsible for excessive cell growth in cancer, enabling transcriptional activation of genes involved in cell cycle regulation, metabolism, and apoptosis, and is usually overexpressed in gastric cancer (GC). By using siRNA and Next-Generation Sequencing (NGS), we identified MYC-regulated differentially expressed Genes (DEGs) in three Brazilian gastric cancer cell lines representing the histological subtypes of GC (diffuse, intestinal, and metastasis). The DEGs were picked using Sailfish software, followed by Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using KEGG. We found 11 significantly enriched gene sets by using enrichment score (ES), False Discovery Rate (FDR), and nominal P-values. We identified a total of 5.471 DEGs with correlation over (80%). In diffuse-type and in metastatic GC cell lines, MYC-silencing caused DEGs downregulation, while the intestinal-type GC cells presented overall DEGs upregulation after MYC siRNA depletion. We were able to detect 11 significant gene sets when comparing our samples to the hallmark collection of gene expression, enriched mostly for the following hallmarks: proliferation, pathway, signaling, metabolic, and DNA damage response. When we analyzed our DEGs considering KEGG metabolic pathways, we found 12 common branches covering a wide range of biological functions, and three of them were common to all three cell lines: ubiquitin-mediated proteolysis, ribosomes, and system and epithelial cell signaling in Helicobacter pylori infection. The GC cell lines used in this study share 14 MYC-regulated genes, but their gene expression profile is different for each histological subtype of GC. Our results present a computational analysis of MYC-related signatures in GC, and we present evidence that GC cell lines representing distinct histological subtypes of this disease have different MYC-regulated expression profiles but share a common core of altered genes. This is an important step towards the understanding of MYC's role in gastric carcinogenesis and an indication of probable new drug targets in stomach cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Genes myc/genética , Neoplasias Gástricas/genética , Brasil , Carcinogênese/genética , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Humanos , Interferência de RNA , Transdução de Sinais/genética
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