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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.
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Antioxidantes , Coffea , Humanos , Antioxidantes/farmacología , Antioxidantes/química , Cafeína/farmacología , Cafeína/química , Ácido Clorogénico/farmacología , Ácido Clorogénico/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Fenoles/farmacología , Antibacterianos/farmacología , Coffea/químicaRESUMEN
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.
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COVID-19 , Enfermedades Metabólicas , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Prueba de COVID-19 , Estudios Transversales , Brasil , Metaboloma , Metabolómica/métodos , Biomarcadores , Amidas , IonesRESUMEN
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.
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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.
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Solanum lycopersicum , Algoritmos , Inocuidad de los Alimentos , Solanum lycopersicum/química , Aprendizaje Automático , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
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.
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Líquido Folicular , Infertilidad Femenina , Femenino , Humanos , Embarazo , Fertilización In Vitro , Metabolómica , Biomarcadores , Infertilidad Femenina/terapiaRESUMEN
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.
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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.
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COVID-19 , MicroARNs , Brasil/epidemiología , COVID-19/genética , Perfilación de la Expresión Génica/métodos , Humanos , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/genética , SARS-CoV-2 , beta Catenina/genéticaRESUMEN
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.
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Strongyloides stercoralis , Estrongiloidiasis , Animales , Biomarcadores , Heces/parasitología , Humanos , Estrongiloidiasis/epidemiologíaRESUMEN
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.
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Enfermedades del Sistema Nervioso , Infección por el Virus Zika , Virus Zika , Animales , Femenino , Humanos , Ratones , Placenta , Embarazo , Replicación Viral , Infección por el Virus Zika/complicacionesRESUMEN
The Estudo de Descontinuação de Imatinibe após Pioglitazona (EDI-PIO) is a single-center, longitudinal, prospective, phase 2, non-randomized, open, clinical trial (NCT02852486, August 2, 2016 retrospectively registered) for the discontinuation of imatinib after concomitant use of pioglitazone, being the first of its kind in a Brazilian population with chronic myeloid leukemia. Due to remaining of leukemic quiescent cells that are not affected by tyrosine kinase inhibitors, it has been suggested the use of pioglitazone, a PPARγ agonist, together with imatinib as a strategy for the maintenance of deep molecular response. The clinical benefit to this association is still controversial, and the metabolic alteration along this process remains unclear. Therefore, we applied a metabolomic protocol using high-resolution mass spectrometry to profile plasmatic metabolic response of a prospective cohort of ten individuals under discontinuation of imatinib and pioglitazone protocol. By comparing patients under pioglitazone and imatinib treatment with imatinib monotherapy and discontinuation phase, we were able to annotate 41 and 36 metabolites, respectively. The metabolic alterations observed during imatinib-pioglitazone combined therapy are associated with an extensive lipid remodeling, with activation of ß-oxidation pathway, in addition to the presence of markers that suggest mitochondrial dysfunction.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Enfermedades Metabólicas/patología , Metaboloma , Privación de Tratamiento , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Mesilato de Imatinib/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Estudios Longitudinales , Masculino , Enfermedades Metabólicas/inducido químicamente , Enfermedades Metabólicas/metabolismo , Persona de Mediana Edad , Ensayos Clínicos Controlados no Aleatorios como Asunto , Pioglitazona/administración & dosificación , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
Buritirana (Mauritiella armata Mart.) is a fruit species native to the Amazon and Cerrado region, belonging to the Arecaceae family. It has high nutritional and functional potential, yet little explored. In this study, we evaluated for the first time the overall yield, behavior of total carotenoids in the extraction kinetics, fatty acid profile, bioactive compounds, and the antioxidant capacity of the oil from buritirana fractions obtained by supercritical CO2. The highest extraction yield was found in the pulp and whole without seed at 60 °C (18.06 ± 0.40 and 14.55 ± 1.10 g 100 g-1 of the freeze-dried sample (fdw), respectively), and in the peel at 40 °C (8.31 ± 0.73 g 100 g-1 fdw). During the extraction kinetics, the pulp had the highest yields of oil (41.57%) and total carotenoids (8.34 mg g-1) after 61 min at 40 °C. The antioxidant potential, fatty acid profile, and α-tocopherol content were dependent on both fraction and temperature, with oleic acid being the main fatty acid. The oil from the whole fraction without seed had the largest number (20) of identified phenolic compounds. The extraction at 60 °C reduced the relative intensity of most compounds in the whole without seed and pulp. Moreover, it increased the intensity of the compounds in the peel. These results suggest that buritirana is a good oil source with great bioactive potential to produce new products with functional claims.
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Antioxidantes , Arecaceae , Brasil , Ácidos Grasos , FrutasRESUMEN
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.
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COVID-19/diagnóstico , Aprendizaje Automático , Metabolómica , Adulto , Anciano , Automatización , Biomarcadores/metabolismo , Brasil , COVID-19/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , SARS-CoV-2/aislamiento & purificaciónRESUMEN
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.
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Eugenia , Brasil , Frutas , Nutrientes , Espectrometría de Masas en TándemRESUMEN
Uvaia is a Brazilian native species whose fruit has few studies on the nutritional composition and antioxidant properties. In this study, we evaluated for the first time the proximate composition, mineral content, carbohydrate profile, identification of organic compounds, and determination of antioxidant properties in two fractions of this fruit (edible fraction and seed). Edible fraction showed the highest content of ash, lipids, proteins, total fibers, minerals mainly K and Mg (1557.61 and 124.40 mg 100 g-1, respectively), and carbohydrates such as fructose, sucrose, glucose (123.08; 64.40; and 42.39 mg g-1, respectively), and maltotetraose (G4). From the ESI-LTQ-XL-MS/MS analysis, it was possible to identify 22 compounds in the edible fraction and 16 compounds in the uvaia seed, including organic acids, phenolic acids and flavonoids. On the other hand, uvaia seed had the highest content of total phenolics, flavonoids and antioxidant capacity. These results suggest that this fruit has great potential to be used in industry, with emphasis on making food with functional claims.
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Eugenia , Brasil , Frutas , Nutrientes , Espectrometría de Masas en TándemRESUMEN
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.
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Candidemia , Candidiasis , Infecciones Oportunistas , Antifúngicos/uso terapéutico , Candida , Candidemia/diagnóstico , Candidiasis/diagnóstico , Candidiasis/tratamiento farmacológico , Humanos , LeucotrienosRESUMEN
Brazil and many other Latin American countries are areas of endemicity for different neglected diseases, and the fungal infection paracoccidioidomycosis (PCM) is one of them. Among the clinical manifestations, pneumopathy associated with skin and mucosal lesions is the most frequent. PCM definitive diagnosis depends on yeast microscopic visualization and immunological tests, but both present ambiguous results and difficulty in differentiating PCM from other fungal infections. This research has employed metabolomics analysis through high-resolution mass spectrometry to identify PCM biomarkers in serum samples in order to improve diagnosis for this debilitating disease. To upgrade the biomarker selection, machine learning approaches, using Random Forest classifiers, were combined with metabolomics data analysis. The proposed combination of these two analytical methods resulted in the identification of a set of 19 PCM biomarkers that show accuracy of 97.1%, specificity of 100%, and sensitivity of 94.1%. The obtained results are promising and present great potential to improve PCM definitive diagnosis and adequate pharmacological treatment, reducing the incidence of PCM sequelae and resulting in a better quality of life.IMPORTANCE Paracoccidioidomycosis (PCM) is a fungal infection typically found in Latin American countries, especially in Brazil. The identification of this disease is based on techniques that may fail sometimes. Intending to improve PCM detection in patient samples, this study used the combination of two of the newest technologies, artificial intelligence and metabolomics. This combination allowed PCM detection, independently of disease form, through identification of a set of molecules present in patients' blood. The great difference in this research was the ability to detect disease with better confidence than the routine methods employed today. Another important point is that among the molecules, it was possible to identify some indicators of contamination and other infection that might worsen patients' condition. Thus, the present work shows a great potential to improve PCM diagnosis and even disease management, considering the possibility to identify concomitant harmful factors.
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Weight gain is a metabolic disorder that often culminates in the development of obesity and other comorbidities such as diabetes. Obesity is characterized by the development of a chronic, subclinical systemic inflammation, and is regarded as a remarkably important factor that contributes to the development of such comorbidities. Therefore, laboratory methods that allow the identification of subjects at higher risk for severe weight-associated morbidity are of utter importance, considering the health, and safety of populations. This contribution analyzed the plasma of 180 Brazilian individuals, equally divided into a eutrophic control group and case group, to assess the presence of biomarkers related to weight gain, aiming at characterizing the phenotype of this population. Samples were analyzed by mass spectrometry and most discriminant features were determined by a machine learning approach using Random Forest algorithm. Five biomarkers related to the pathogenesis and chronicity of inflammation in weight gain were identified. Two metabolites of arachidonic acid were upregulated in the case group, indicating the presence of inflammation, as well as two other molecules related to dysfunctions in the cycle of nitric oxide (NO) and increase in superoxide production. Finally, a fifth case group marker observed in this study may indicate the trigger for diabetes in overweight and obesity individuals. The use of mass spectrometry combined with machine learning analyses to prospect and characterize biomarkers associated with weight gain will pave the way for elucidating potential therapeutic and prognostic targets.
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The recent outbreak of Zika virus (ZIKV) infection associated with microcephaly cases has elicited much research on the mechanisms involved in ZIKV-host cell interactions. It has been described that Zika virus impairs cell growth, raising a hypothesis about its oncolytic potential against cancer cells. ZIKV tumor cell growth inhibition was later confirmed for glioblastoma. It was also demonstrated that an inactivated ZIKV prototype (ZVp) based on bacterial outer membrane vesicles has antiproliferative activity upon other cancer cell lines, such as PC-3 prostate cancer cell. This study aims at understanding the pathways that might be involved with the antiproliferative effect of Zika virus against prostate cancer cells. A metabolomic approach based on high-resolution mass spectrometry analysis led to the identification of 21 statistically relevant markers of PC-3 cells treated with ZVp. The markers were associated with metabolic alterations that trigger lipid remodeling, endoplasmic reticulum stress, inflammatory mediators, as well as disrupted porphyrin and folate metabolism. These findings highlight molecular signatures of ZVp-induced response that may be involved on cellular pathways triggered by its antiproliferative effect. To our knowledge, this is the first reported metabolomic assessment of ZIKV effect on prostate cancer cells, a promising topic for further research.
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Neoplasias de la Próstata/genética , Neoplasias de la Próstata/virología , Inactivación de Virus , Virus Zika/fisiología , Análisis Discriminante , Humanos , Análisis de los Mínimos Cuadrados , Metabolismo de los Lípidos , Masculino , Células PC-3RESUMEN
GPR120 and GPR40 were recently reported as omega-3 (ω3) receptors with anti-inflammatory properties. Physical exercise could increase the expression of these receptors in the liver, improving hepatic metabolism in obesity and type 2 diabetes. Our aim was to investigate GPR120/40 in the liver of lean and obese mice after acute or chronic physical exercise, with or without the supplementation of ω3 rich flaxseed oil (FS), as well as assess the impact of exercise and FS on insulin signaling and inflammation. Mice were fed a high-fat diet (HF) for 4 weeks to induce obesity and subsequently subjected to exercise with or without FS, or FS alone. Insulin signaling, inflammatory markers and GPR120/40 and related cascades were measured. Chronic, but not acute, exercise and FS increased GPR120, but not GPR40, activating ß-arrestin-2 and decreasing the inflammatory response, as well as reducing fat depots in liver and adipose tissue. Exercise or a source of ω3 led to a higher tolerance to fatigue and an increased running distance and speed. The combination of physical exercise and ω3 food sources could provide a new strategy against obesity through the modulation of hepatic GPR120 and an increase in exercise performance.
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Ácidos Grasos Insaturados/farmacología , Aceite de Linaza/química , Hígado/efectos de los fármacos , Receptores Acoplados a Proteínas G/metabolismo , Tejido Adiposo , Animales , Antiinflamatorios no Esteroideos/farmacología , Dieta Alta en Grasa/efectos adversos , Prueba de Tolerancia a la Glucosa , Insulina/metabolismo , Resistencia a la Insulina , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Obesidad/dietoterapia , Obesidad/metabolismo , Condicionamiento Físico AnimalRESUMEN
Falsified, counterfeit and adulterated medicines are an endemic problem worldwide that results in both monetary and health-related losses. Developing fast and reliable methods that are able to present a timely result based on the drug's spectral profile is an effort that is sure to benefit those involved in the whole distribution chain. We propose herein a Laser Desorption/Ionization imaging-based method that provides simple and minimal sample preparation; this method is capable of providing specific markers that characterize adulterations, using as proof of concept one of the most adulterated drug products for oral use, sildenafil. Our approach is able to provide quality markers, which can be applied in the fast screening of any product within the same molecular class. This same strategy may be a useful alternative to provide accurate measurements with high specificity for unraveling contaminants and/or byproducts in virtually any given pharmaceutical product.