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1.
Mol Biol Rep ; 49(7): 6931-6943, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35301654

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is known that host microRNAs (miRNAs) can be modulated to favor viral infection or to protect the host. Herein, we report preliminary results of a study aiming at identifying differentially expressed plasmatic miRNAs in Brazilian patients with COVID-19. METHODS AND RESULTS: miRNAs were extracted from the plasma of eight patients with COVID-19 (four patients with mild COVID-19 and four patients with severe/critical COVID-19) and four healthy controls. Patients and controls were matched for sex and age. miRNA expression levels were detected using high-throughput sequencing. Differential miRNA expression and enrichment analyses were further evaluated. A total of 18 miRNAs were differentially expressed between patients with COVID-19 and controls. miR-4433b-5p, miR-6780b-3p, miR-6883-3p, miR-320b, miR-7111-3p, miR-4755-3p, miR-320c, and miR-6511a-3p were the most important miRNAs significantly involved in the PI3K/AKT, Wnt/ß-catenin, and STAT3 signaling pathways. Moreover, 42 miRNAs were differentially expressed between severe/critical and mild patients with COVID-19. miR-451a, miR-101-3p, miR-185-5p, miR-30d-5p, miR-25-3p, miR-342-3p, miR-30e-5p, miR-150-5p, miR-15b-5p, and miR-29c-3p were the most important miRNAs significantly involved in the Wnt/ß-catenin, NF-κß, and STAT3 signaling pathways. CONCLUSIONS: If validated by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in a larger number of participants, the miRNAs identified in this study might be used as possible biomarkers for the diagnosis and severity of COVID-19.


Assuntos
COVID-19 , MicroRNAs , Brasil/epidemiologia , COVID-19/genética , Perfilação da Expressão Gênica/métodos , Humanos , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/genética , SARS-CoV-2 , beta Catenina/genética
2.
Anal Chem ; 93(4): 2471-2479, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33471512

RESUMO

COVID-19 is still placing a heavy health and financial burden worldwide. Impairment in patient screening and risk management plays a fundamental role on how governments and authorities are directing resources, planning reopening, as well as sanitary countermeasures, especially in regions where poverty is a major component in the equation. An efficient diagnostic method must be highly accurate, while having a cost-effective profile. We combined a machine learning-based algorithm with mass spectrometry to create an expeditious platform that discriminate COVID-19 in plasma samples within minutes, while also providing tools for risk assessment, to assist healthcare professionals in patient management and decision-making. A cross-sectional study enrolled 815 patients (442 COVID-19, 350 controls and 23 COVID-19 suspicious) from three Brazilian epicenters from April to July 2020. We were able to elect and identify 19 molecules related to the disease's pathophysiology and several discriminating features to patient's health-related outcomes. The method applied for COVID-19 diagnosis showed specificity >96% and sensitivity >83%, and specificity >80% and sensitivity >85% during risk assessment, both from blinded data. Our method introduced a new approach for COVID-19 screening, providing the indirect detection of infection through metabolites and contextualizing the findings with the disease's pathophysiology. The pairwise analysis of biomarkers brought robustness to the model developed using machine learning algorithms, transforming this screening approach in a tool with great potential for real-world application.


Assuntos
COVID-19/diagnóstico , Aprendizado de Máquina , Metabolômica , Adulto , Idoso , Automação , Biomarcadores/metabolismo , Brasil , COVID-19/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , SARS-CoV-2/isolamento & purificação
3.
Brain Behav Immun ; 97: 260-274, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34390806

RESUMO

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.


Assuntos
Doenças do Sistema Nervoso , Infecção por Zika virus , Zika virus , Animais , Feminino , Humanos , Camundongos , Placenta , Gravidez , Replicação Viral , Infecção por Zika virus/complicações
4.
Microb Pathog ; 149: 104394, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32707317

RESUMO

Candidiasis is the most common fungal infection affecting hospitalized patients, especially immunocompromised and critical patients. Limitations regarding the assertive diagnosis of both Candidemia and Candidiasis not only impairs the introduction of effective treatments but also lays a heavy financial burden over the health system. Furthermore, it is still challenging to ascertain whether diagnostic methods are accurate and whether treatment is effective for patients with Candidemia. These constraints come from the uncertainty of the pathophysiological mechanism by which the pathogen establishes the opportunistic infection. Additionally, it is the reason why some patients present positive blood culture results, and others do not, and why it is very difficult during clinical routines to prove Candidemia or invasive candidiasis. Taking into account the current situation, this contribution proposes two markers that may help to understand the mechanisms of infection by the pathogen: Leukotriene F4 and 5,6-dihydroxy-eicosatetraenoic. These two lipids putatively modulate the host's immune response, and the initial data presented in this contribution suggest that these lipids allow the opportunistic infection to be installed. The study was carried out using an omics-based platform using direct-infusion high-resolution mass spectrometry and allied with bioinformatics tools to provide accurate and reliable results for biomarker candidates screening.


Assuntos
Candidemia , Candidíase , Infecções Oportunistas , Antifúngicos/uso terapêutico , Candida , Candidemia/diagnóstico , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Humanos , Leucotrienos
5.
Eur J Nutr ; 56(8): 2541-2556, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27535559

RESUMO

PURPOSE: Yerba maté is widely consumed in South America as different beverages, such as maté tea (roasted leaves) and chimarrão (green dried leaves), and linked to health benefits, mainly attributed to chlorogenic acids (CGAs). Health effects of CGAs depend on their bioavailability, but such data are scarce. The aim of this study was to investigate the distribution of CGAs and metabolites in tissues, hepatic and plasmatic kinetic profile and urinary excretion after ingestion of maté tea or 5-caffeoylquinic acid (5-CQA). METHODS: Wistar rats ingested maté tea (MT) or 5-CQA (ST) and were killed after 1.5 h for tissue distribution analysis (pilot study) or at 0.5, 1, 2, 4 and 8 h for liver and plasma kinetics (main experiment). Urine was collected in metabolic cages. Biological samples were analyzed by UPLC-DAD-MS with and without incubation with ß-glucuronidase and sulfatase. RESULTS: CGAs and metabolites were detected in all tissues. Caffeic acid was the main compound in plasma up to 2 h after ingestion of maté tea, while 5-CQA predominated in ST group. Concentration of microbial metabolites increased 4 h after gavage and reached higher amounts in MT plasma and liver, when compared to ST group. Approximately 4.0 % of compounds ingested by MT and 3.3 % by ST were recovered in urine up to 8 h after the gavage. CONCLUSION: The study confirms that not only absorption, but also metabolization of CGAs begins in stomach. There were differences in compounds formed from maté tea or isolated 5-CQA, showing that CGAs profile in food may influence qualitatively and quantitatively the metabolites formed in the body.


Assuntos
Ácido Clorogênico/farmacocinética , Ilex paraguariensis/química , Ácido Quínico/análogos & derivados , Chás de Ervas , Animais , Disponibilidade Biológica , Ácidos Cafeicos/sangue , Ácido Clorogênico/administração & dosagem , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacocinética , Folhas de Planta/química , Polifenóis/administração & dosagem , Polifenóis/farmacocinética , Polifenóis/urina , Ácido Quínico/administração & dosagem , Ácido Quínico/farmacocinética , Ratos , Ratos Wistar , América do Sul
6.
Parasitol Res ; 115(11): 4107-4114, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27412760

RESUMO

Ascaris lumbricoides is responsible for a highly disseminated helminth parasitic disease, ascariosis, a relevant parasitosis that responds for great financial burden on the public health system of developing countries. In this work, metabolic fingerprinting using high-resolution mass spectrometry (HRMS) was employed to identify marker molecules from A. lumbricoides in different development stages. We have identified nine biomarkers, such as pheromones and steroidal prohormones in early stages, among other molecules in late development stages, making up four molecules for fertilized eggs, four marker molecules for first larvae (L1) and one marker molecule for third larvae (L3). Therefore, our findings indicate that this approach is suitable for biochemical characterization of A. lumbricoides development stages. Moreover, the straightforward analytical method employed, with almost no sample preparation from a complex matrix (feces) using high-resolution mass spectrometry, suggests that it is possible to seek for an easier and faster way to study animal molding processes.


Assuntos
Ascaríase/parasitologia , Ascaris lumbricoides/crescimento & desenvolvimento , Espectrometria de Massas/métodos , Metabolômica , Animais , Ascaris lumbricoides/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Fezes/parasitologia , Feminino , Humanos , Larva , Masculino
7.
Anal Chem ; 87(7): 3585-92, 2015 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-25785304

RESUMO

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which primarily infects macrophages and Schwann cells, affecting skin and peripheral nerves. Clinically, the most common form of identification is through the observation of anesthetic lesions on skin; however, up to 30% of infected patients may not present this clinical manifestation. Currently, the gold standard diagnostic test for leprosy is based on skin lesion biopsy, which is invasive and presents low sensibility for suspect cases. Therefore, the development of a fast, sensible and noninvasive method that identifies infected patients would be helpful for assertive diagnosis. The aim of this work was to identify lipid markers in leprosy patients directly from skin imprints, using a mass spectrometric analytical strategy. For skin imprint samples, a 1 cm(2) silica plate was gently pressed against the skin of patients or healthy volunteers. Imprinted silica lipids were extracted and submitted to direct-infusion electrospray ionization high-resolution mass spectrometry (ESI-HRMS). All samples were differentiated using a lipidomics-based data workup employing multivariate data analysis, which helped electing different lipid markers, for example, mycobacterial mycolic acids, inflammatory and apoptotic molecules were identified as leprosy patients' markers. Otherwise, phospholipids and gangliosides were pointed as healthy volunteers' skin lipid markers, according to normal skin composition. Results indicate that silica plate skin imprinting associated with ESI-HRMS is a promising fast and sensible leprosy diagnostic method. With a prompt leprosy diagnosis, an early and effective treatment could be feasible and thus the chain of leprosy transmission could be abbreviated.


Assuntos
Hanseníase/diagnóstico , Lipídeos/análise , Mycobacterium leprae/isolamento & purificação , Dióxido de Silício/química , Pele/microbiologia , Pele/patologia , Espectrometria de Massas por Ionização por Electrospray/métodos , Adolescente , Adulto , Biomarcadores/análise , Humanos , Hanseníase/patologia , Lipídeos/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
J Nanobiotechnology ; 13: 78, 2015 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-26518450

RESUMO

BACKGROUND: The blood-brain barrier (BBB) is a complex physical and functional barrier protecting the central nervous system from physical and chemical insults. Nevertheless, it also constitutes a barrier against therapeutics for treating neurological disorders. In this context, nanomaterial-based therapy provides a potential alternative for overcoming this problem. Graphene family has attracted significant interest in nanomedicine because their unique physicochemical properties make them amenable to applications in drug/gene delivery and neural interface. RESULTS: In this study, reduced graphene oxide (rGO) systemically-injected was found mainly located in the thalamus and hippocampus of rats. The entry of rGO involved a transitory decrease in the BBB paracellular tightness, as demonstrated at anatomical (Evans blue dye infusion), subcellular (transmission electron microscopy) and molecular (junctional protein expression) levels. Additionally, we examined the usefulness of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) as a new imaging method for detecting the temporal distribution of nanomaterials throughout the brain. CONCLUSIONS: rGO was able to be detected and monitored in the brain over time provided by a novel application for MALDI-MSI and could be a useful tool for treating a variety of brain disorders that are normally unresponsive to conventional treatment because of BBB impermeability.


Assuntos
Barreira Hematoencefálica/metabolismo , Grafite/farmacologia , Óxidos/farmacologia , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/ultraestrutura , Western Blotting , Capilares/ultraestrutura , Hipocampo/ultraestrutura , Masculino , Microscopia Confocal , Modelos Biológicos , Oxirredução , Ratos Wistar , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrofotometria Ultravioleta , Frações Subcelulares/metabolismo , Distribuição Tecidual/efeitos dos fármacos
9.
Anal Chem ; 86(7): 3415-9, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24451041

RESUMO

Plant biomass has been suggested as an alternative to produce bioethanol. The recalcitrance of plant biomass to convert cellulose into simpler carbohydrates used in the fermentation process is partially due to lignin, but the standard methods used to analyze lignin composition frequently use toxic solvents and are laborious and time-consuming. MS imaging was used to study lignin in Eucalyptus, since this genus is the main source of cellulose in the world. Hand-cut sections of stems of two Eucalyptus species were covered with silica and directly analyzed by matrix-assisted laser sesorption ionization (MALDI)-imaging mass spectrometry (MS). Information available in the literature about soluble lignin subunits and structures were used to trace their distribution in the sections and using a software image a relative quantification could be made. Matrixes routinely used in MALDI-imaging analysis are not satisfactory to analyze plant material and were efficiently substituted by thin layer chromatography (TLC) grade silica. A total of 22 compounds were detected and relatively quantified. It was also possible to establish a proportion between syringyl and guaiacyl monolignols, characteristic for each species. Because of the simple way that samples are prepared, the MALDI-imaging approach presented here can replace, in routine analysis, complex and laborious MS methods in the study of lignin composition.


Assuntos
Eucalyptus/química , Lignina/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Cromatografia em Camada Fina
10.
Sci Rep ; 14(1): 4453, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396007

RESUMO

Consumer demand for natural, chemical-free products has grown. Food industry residues, like coffee pulp, rich in caffeine, chlorogenic acid and phenolic compounds, offer potential for pharmaceutical and cosmetic applications due to their antioxidant, anti-inflammatory, and antibacterial properties. Therefore, the objective of this work was to develop a phytocosmetic only with natural products containing coffee pulp extract as active pharmaceutical ingredient with antioxidant, antimicrobial and healing activity. Eight samples from Coffea arabica and Coffea canephora Pierre were analyzed for caffeine, chlorogenic acid, phenolic compounds, tannins, flavonoids, cytotoxicity, antibacterial activity, and healing potential. The Robusta IAC-extract had the greatest prominence with 192.92 µg/mL of chlorogenic acid, 58.98 ± 2.88 mg GAE/g sample in the FRAP test, 79.53 ± 5.61 mg GAE/g sample in the test of total phenolics, was not cytotoxic, and MIC 3 mg/mL against Staphylococcus aureus. This extract was incorporated into a stable formulation and preferred by 88% of volunteers. At last, a scratch assay exhibited the formulation promoted cell migration after 24 h, therefore, increased scratch retraction. In this way, it was possible to develop a phytocosmetic with the coffee pulp that showed desirable antioxidant, antimicrobial and healing properties.


Assuntos
Antioxidantes , Coffea , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Cafeína/farmacologia , Cafeína/química , Ácido Clorogênico/farmacologia , Ácido Clorogênico/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Fenóis/farmacologia , Antibacterianos/farmacologia , Coffea/química
11.
J Mol Med (Berl) ; 102(2): 183-195, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38010437

RESUMO

As SARS-CoV-2 continues to produce new variants, the demand for diagnostics and a better understanding of COVID-19 remain key topics in healthcare. Skin manifestations have been widely reported in cases of COVID-19, but the mechanisms and markers of these symptoms are poorly described. In this cross-sectional study, 101 patients (64 COVID-19 positive patients and 37 controls) were enrolled between April and June 2020, during the first wave of COVID-19, in São Paulo, Brazil. Enrolled patients had skin imprints sampled non-invasively using silica plates; plasma samples were also collected. Samples were used for untargeted lipidomics/metabolomics through high-resolution mass spectrometry. We identified 558 molecular ions, with lipids comprising most of them. We found 245 plasma ions that were significant for COVID-19 diagnosis, compared to 61 from the skin imprints. Plasma samples outperformed skin imprints in distinguishing patients with COVID-19 from controls, with F1-scores of 91.9% and 84.3%, respectively. Skin imprints were excellent for assessing disease severity, exhibiting an F1-score of 93.5% when discriminating between patient hospitalization and home care statuses. Specifically, oleamide and linoleamide were the most discriminative biomarkers for identifying hospitalized patients through skin imprinting, and palmitic amides and N-acylethanolamine 18:0 were also identified as significant biomarkers. These observations underscore the importance of primary fatty acid amides and N-acylethanolamines in immunomodulatory processes and metabolic disorders. These findings confirm the potential utility of skin imprinting as a valuable non-invasive sampling method for COVID-19 screening; a method that may also be applied in the evaluation of other medical conditions. KEY MESSAGES: Skin imprints complement plasma in disease metabolomics. The annotated markers have a role in immunomodulation and metabolic diseases. Skin imprints outperformed plasma samples at assessing disease severity. Skin imprints have potential as non-invasive sampling strategy for COVID-19.


Assuntos
COVID-19 , Doenças Metabólicas , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Teste para COVID-19 , Estudos Transversais , Brasil , Metaboloma , Metabolômica/métodos , Biomarcadores , Amidas , Íons
13.
Food Chem ; 398: 133870, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35963216

RESUMO

Food safety and quality assessment mechanisms are unmet needs that industries and countries have been continuously facing in recent years. Our study aimed at developing a platform using Machine Learning algorithms to analyze Mass Spectrometry data for classification of tomatoes on organic and non-organic. Tomato samples were analyzed using silica gel plates and direct-infusion electrospray-ionization mass spectrometry technique. Decision Tree algorithm was tailored for data analysis. This model achieved 92% accuracy, 94% sensitivity and 90% precision in determining to which group each fruit belonged. Potential biomarkers evidenced differences in treatment and production for each group.


Assuntos
Solanum lycopersicum , Algoritmos , Inocuidade dos Alimentos , Solanum lycopersicum/química , Aprendizado de Máquina , Espectrometria de Massas por Ionização por Electrospray
14.
World J Hepatol ; 15(11): 1237-1249, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38075010

RESUMO

BACKGROUND: Chronic Hepatitis C (CHC) affects 71 million people globally and leads to liver issues such as fibrosis, cirrhosis, cancer, and death. A better understanding and prognosis of liver involvement are vital to reduce morbidity and mortality. The accurate identification of the fibrosis stage is crucial for making treatment decisions and predicting outcomes. Tests used to grade fibrosis include histological analysis and imaging but have limitations. Blood markers such as molecular biomarkers can offer valuable insights into fibrosis. AIM: To identify potential biomarkers that might stratify these lesions and add information about the molecular mechanisms involved in the disease. METHODS: Plasma samples were collected from 46 patients with hepatitis C and classified into fibrosis grades F1 (n = 13), F2 (n = 12), F3 (n = 6), and F4 (n = 15). To ensure that the identified biomarkers were exclusive to liver lesions (CHC fibrosis), healthy volunteer participants (n = 50) were also included. An untargeted metabolomic technique was used to analyze the plasma metabolites using mass spectrometry and database verification. Statistical analyses were performed to identify differential biomarkers among groups. RESULTS: Six differential metabolites were identified in each grade of fibrosis. This six-metabolite profile was able to establish a clustering tendency in patients with the same grade of fibrosis; thus, they showed greater efficiency in discriminating grades. CONCLUSION: This study suggests that some of the observed biomarkers, once validated, have the potential to be applied as prognostic biomarkers. Furthermore, it suggests that liquid biopsy analyses of plasma metabolites are a good source of molecular biomarkers capable of stratifying patients with CHC according to fibrosis grade.

15.
Acta Trop ; 227: 106279, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34968451

RESUMO

Strongyloidiasis, a parasitosis caused by Strongyloides stercoralis in humans, is a very prevalent infection in tropical or subtropical areas. Gaps on public health strategies corroborates to the high global incidence of strongyloidiasis especially due to challenges involved on its diagnosis. Based on the lack of a gold-standard diagnostic tool, we aimed to present a metabolomic study for the assessment of stool metabolic alterations. Stool samples were collected from 25 patients segregated into positive for strongyloidiasis (n = 10) and negative control (n = 15) and prepared for direct injection high-resolution mass spectrometry analysis. Using metabolomics workflow, 18 metabolites were annotated increased or decreased in strongyloidiasis condition, from which a group of 5 biomarkers comprising caprylic acid, mannitol, glucose, lysophosphatidylinositol and hydroxy-dodecanoic acid demonstrated accuracy over 89% to be explored as potential markers. The observed metabolic alteration in stool samples indicates involvement of microbiota remodeling, parasite constitution, and host response during S. stercoralis infection.


Assuntos
Strongyloides stercoralis , Estrongiloidíase , Animais , Biomarcadores , Fezes/parasitologia , Humanos , Estrongiloidíase/epidemiologia
16.
Sci Rep ; 12(1): 20531, 2022 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-36446837

RESUMO

Infertility is a worldwide concern, affecting one in six couples throughout their reproductive period. Therefore, enhancing the clinical tools available to identify the causes of infertility may save time, money, and emotional distress for the involved parties. This study aims to annotate potential biomarkers in follicular fluid that are negatively affecting pregnancy outcomes in women suffering infertility-related diseases such as endometriosis, tuboperitoneal factor, uterine factor, and unexplained infertility, using a metabolomics approach through high-resolution mass spectrometry. Follicular fluid samples collected from women who have the abovementioned diseases and managed to become pregnant after in vitro fertilization procedures [control group (CT)] were metabolically compared with those from women who suffer from the same diseases and could not get pregnant after the same treatment [infertile group (IF)]. Mass spectrometry analysis indicated 10 statistically relevant differential metabolites in the IF group, including phosphatidic acids, phosphatidylethanolamines, phosphatidylcholines, phosphatidylinositol, glucosylceramides, and 1-hydroxyvitamin D3 3-D-glucopyranoside. These metabolites are associated with cell signaling, cell proliferation, inflammation, oncogenesis, and apoptosis, and linked to infertility problems. Our results indicate that understanding the IF's metabolic profile may result in a faster and more assertive female infertility diagnosis, lowering the costs, and increasing the probability of a positive pregnancy outcome.


Assuntos
Líquido Folicular , Infertilidade Feminina , Feminino , Humanos , Gravidez , Fertilização in vitro , Metabolômica , Biomarcadores , Infertilidade Feminina/terapia
17.
Front Microbiol ; 13: 844283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572676

RESUMO

The severity, disabilities, and lethality caused by the coronavirus 2019 (COVID-19) disease have dumbfounded the entire world on an unprecedented scale. The multifactorial aspect of the infection has generated interest in understanding the clinical history of COVID-19, particularly the classification of severity and early prediction on prognosis. Metabolomics is a powerful tool for identifying metabolite signatures when profiling parasitic, metabolic, and microbial diseases. This study undertook a metabolomic approach to identify potential metabolic signatures to discriminate severe COVID-19 from non-severe COVID-19. The secondary aim was to determine whether the clinical and laboratory data from the severe and non-severe COVID-19 patients were compatible with the metabolomic findings. Metabolomic analysis of samples revealed that 43 metabolites from 9 classes indicated COVID-19 severity: 29 metabolites for non-severe and 14 metabolites for severe disease. The metabolites from porphyrin and purine pathways were significantly elevated in the severe disease group, suggesting that they could be potential prognostic biomarkers. Elevated levels of the cholesteryl ester CE (18:3) in non-severe patients matched the significantly different blood cholesterol components (total cholesterol and HDL, both p < 0.001) that were detected. Pathway analysis identified 8 metabolomic pathways associated with the 43 discriminating metabolites. Metabolomic pathway analysis revealed that COVID-19 affected glycerophospholipid and porphyrin metabolism but significantly affected the glycerophospholipid and linoleic acid metabolism pathways (p = 0.025 and p = 0.035, respectively). Our results indicate that these metabolomics-based markers could have prognostic and diagnostic potential when managing and understanding the evolution of COVID-19.

18.
Brain Stimul ; 15(3): 780-788, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35568312

RESUMO

BACKGROUND AND PURPOSE: Acute Respiratory Distress Syndrome (ADRS) due to coronavirus disease 2019 (COVID-19) has been associated with muscle fatigue, corticospinal pathways dysfunction, and mortality. High-Definition transcranial Direct Current Stimulation (HD-tDCS) may be used to attenuate clinical impairment in these patients. The HD-RECOVERY randomized clinical trial was conducted to evaluate the efficacy and safety of HD-tDCS with respiratory rehabilitation in patients with moderate to severe ARDS due to COVID-19. METHODS: Fifty-six critically ill patients were randomized 1:1 to active (n = 28) or sham (n = 28) HD-tDCS (twice a day, 30-min, 3-mA) plus respiratory rehabilitation for up to 10 days or until intensive care unit discharge. The primary outcome was ventilator-free days during the first 28 days, defined as the number of days free from mechanical ventilation. Furthermore, secondary outcomes such as delirium, organ failure, hospital length of stay and adverse effects were investigated. RESULTS: Active HD-tDCS induced more ventilator-free days compared to sham HD-tDCS. Patients in the active group vs in the sham group experienced lower organ dysfunction, delirium, and length of stay rates over time. In addition, positive clinical response was higher in the active vs sham group. There was no significant difference in the prespecified secondary outcomes at 5 days. Adverse events were similar between groups. CONCLUSIONS: Among patients with COVID-19 and moderate to severe ARDS, use of active HD-tDCS compared with sham HD-tDCS plus respiratory rehabilitation resulted in a statistically significant increase in the number of ventilator-free days over 28 days. HD-tDCS combined with concurrent rehabilitation therapy is a safe, feasible, potentially add-on intervention, and further trials should examine HD-tDCS efficacy in a larger sample of patients with COVID-19 and severe hypoxemia.


Assuntos
COVID-19 , Delírio , Síndrome do Desconforto Respiratório , Estimulação Transcraniana por Corrente Contínua , Estado Terminal/terapia , Delírio/etiologia , Humanos , Síndrome do Desconforto Respiratório/terapia , SARS-CoV-2 , Estimulação Transcraniana por Corrente Contínua/efeitos adversos
19.
Br J Nutr ; 105(5): 694-702, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21324234

RESUMO

The goal of the present study was to investigate whether subchronic treatment with grape juice concentrate is able to protect liver and peripheral blood cells against cholesterol-induced injury in rats. The effects of the grape juice concentrate treatment on histopathological changes, immunohistochemistry for cyclo-oxygenase-2 (COX-2), and basal and oxidative DNA damage induced by H2O2 using a single-cell gel (comet) assay were evaluated. Male Wistar rats (n 18) were divided into three groups: group 1--negative control; group 2--cholesterol at 1 % (w/w) in their diet, treated for 5 weeks; group 3--cholesterol at 1 % in their chow, treated for 5 weeks, and grape juice concentrate at 222 mg/d in their drinking-water in the final week only. The results indicated that the treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in group 3 compared with group 2. However, grape juice concentrate was able to decrease oxidative DNA damage induced by H2O2 in peripheral blood cells, as depicted by the tail moment results. COX-2 expression in the liver did not show statistically significant differences (P>0·05) between groups. Taken together, the present results suggest that the administration of subchronic grape juice concentrate prevents oxidative DNA damage in peripheral blood cells.


Assuntos
Antioxidantes/farmacologia , Células Sanguíneas/efeitos dos fármacos , Dano ao DNA , Hipercolesterolemia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Vitis , Animais , Antioxidantes/uso terapêutico , Colesterol na Dieta/efeitos adversos , Ensaio Cometa , Ciclo-Oxigenase 2/metabolismo , Dieta Aterogênica , Frutas , Peróxido de Hidrogênio , Hipercolesterolemia/imunologia , Hipercolesterolemia/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Preparações de Plantas/farmacologia , Preparações de Plantas/uso terapêutico , Ratos , Ratos Wistar
20.
Food Res Int ; 139: 109904, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33509473

RESUMO

Eugenia stipitata is a fruit native to the Brazilian Amazonian region, belonging to the Myrtaceae family whose chemical composition has been little evidenced. In this study, we evaluated for the first time the nutritional composition, bioactive compounds and antioxidant properties of two fractions of this fruit. It was observed that the edible fraction had a higher content of minerals such as K, Ca and Mg (827.66 ± 14.51; 107.16 ± 1.54; and 75.65 ± 1.28 mg 100 g-1 dw, respectively), sucrose (38.01 ± 2.94 mg g-1 dw), fructose (17.58 ± 0.80 mg g-1 dw), and maltotetraose (1.63 ± 0.09 mg g-1 dw). In this same fraction, about 30 volatile compounds were found, mainly biciclo(3.2.1)octan-3-one, 6 (2-hydroxyethyl)-, endo-; butanoic acid, 2-methyl-, hexyl ester and p-ocimene. In turn, the seed had the highest number of compounds identified by ESI-LTQ-MS/MS (including vanillic acid, gallic acid hexoside, catechin hexoside, luteolin hexoside, among others), higher content of phenolics (142.43 ± 0.82 mg GAE g-1 dw), flavonoids (43.73 ± 0.23 mg CE g-1 dw), and antioxidant capacity (139.59 ± 2.47; 447.94 ± 2.70; and 100.07 ± 10.50 µM TE g-1 dw for DPPH, ABTS, and ORAC, respectively). These results suggest that Eugenia stipitata has excellent nutritional value and great functional potential, and may contribute to a greater commercial exploitation of this fruit, not only in food, but also in the pharmaceutical and cosmetic industries.


Assuntos
Eugenia , Brasil , Frutas , Nutrientes , Espectrometria de Massas em Tandem
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