Papers by Joseph A. Medeiros Evaristo
Laboratory Investigation, Jul 1, 2023
Revista Brasileira de Farmacognosia, Dec 28, 2021
Proteomics Clinical Applications, Jun 17, 2023
PurposeOur main goal is to identify the alterations in the amniotic fluid (AF) metabolome in Zika... more PurposeOur main goal is to identify the alterations in the amniotic fluid (AF) metabolome in Zika virus (ZIKV)‐infected patients and their relation to congenital Zika syndrome (CZS) progression.Experimental DesignWe applied an untargeted metabolomics strategy to analyze seven AF of pregnant women: healthy women and ZIKV‐infected women bearing non‐microcephalic and microcephalic fetuses.ResultsInfected patients were characterized by glycerophospholipid metabolism impairment, which is accentuated in microcephalic phenotypes. Glycerophospholipid decreased concentration in AF can be a consequence of intracellular transport of lipids to the placental or fetal tissues under development. The increased intracellular concentration of lipids can lead to mitochondrial dysfunction and neurodegeneration caused by lipid droplet accumulation. Furthermore, the dysregulation of amino acid metabolism was a molecular fingerprint of microcephalic phenotypes, specifically serine, and proline metabolisms. Both amino acid deficiencies were related to neurodegenerative disorders, intrauterine growth retardation, and placental abnormalities.Conclusions and Clinical RelevanceThis study enhances our understanding of the development of CZS pathology and sheds light on dysregulated pathways that could be relevant for future studies.
The Journal of Steroid Biochemistry and Molecular Biology, Oct 1, 2018
Highlights Testosterone therapy, even in very low doses, promotes alteration in different metab... more Highlights Testosterone therapy, even in very low doses, promotes alteration in different metabolic pathways Testosterone therapy in old rats, but not in adults, even in very low doses, increases testosterone levels Aged Wistar rats might be a potential animal model to study subclinical hypogonadism Metabolomics and bioinformatics are important tool for testosterone therapy monitoring
Hormone Molecular Biology and Clinical Investigation, Jan 17, 2019
Metabolomics is an emerging technology that is increasing both in basic science and in human appl... more Metabolomics is an emerging technology that is increasing both in basic science and in human applications, providing a physiological snapshot. It has been highlighted as one of the most wide ranging and reliable tools for the investigation of physiological status, the discovery of new biomarkers and the analysis of metabolic pathways. Metabolomics uses innovative mass spectrometry (MS) allied to chromatography or nuclear magnetic resonance (NMR). The recent advances in bioinformatics, databases and statistics, have provided a unique perception of metabolites interaction and the dynamics of metabolic pathways at a system level. In this context, several studies have applied metabolomics in physiology-and disease-related works. The application of metabolomics includes, physiological and metabolic evaluation/monitoring, individual response to different exercise, nutritional interventions, pathological processes, responses to pharmacological interventions, biomarker discovery and monitoring for distinct aspects, such as: physiological capacity, fatigue/recovery and aging among other applications. For metabolomic analyses, despite huge improvements in the field, several complex methodological steps must be taken into consideration. In this regard, the present article aims to summarize the novel aspects of metabolomics and provide a guide for metabolomics for professionals related to physiologist and medical applications.
Microorganisms
The fungicide iprodione (IPR) (3-(3,5-dichlorophenyl) N-isopropyl-2,4-dioxoimidazolidine-1-carbox... more The fungicide iprodione (IPR) (3-(3,5-dichlorophenyl) N-isopropyl-2,4-dioxoimidazolidine-1-carboxamide) is a highly toxic compound. Although IPR has been restricted, it is still being applied in many places around the world, constituting an environmental risk. The biodegradation of IPR is an attractive option for reducing its residues. In this study, we isolated thirteen IPR-tolerant bacteria from a biopurification system designed to treat pesticides. A study of biodegradation using different strains was comparatively evaluated, and the best degradation rate of IPR was presented by Achromobacter sp. C1 with a half-life (T1/2) of 9 days. Based on a nano-LC-MS/MS analysis for the strains, proteins solely expressed in the IPR treatment were identified by highlighting the strain Achromobacter sp. C1, with 445 proteins primarily involved in the biosynthesis of secondary metabolites and microbial metabolism in diverse environments. Differentially expressed protein amidases were involved i...
Experimental Parasitology
Orbital: The Electronic Journal of Chemistry, 2021
The objective of this work was to optimize the culture conditions for laccase production in the p... more The objective of this work was to optimize the culture conditions for laccase production in the presence of Kraft lignin by Fusarium oxysporum JUMAD-053, and to evaluate the biodegradation products of lignin. The fungal isolate that presented highest laccase activity had its production optimized by a statistical factorial design 3 3 in 15 experimental runs. F. oxysporum presented the highest constitutive laccase titer (5.37 U/mL). Statistical factorial design demonstrated a maximum laccase titer of 9.8 U/mL when assayed against ABTS under the conditions optimized: 1.125% (w/v) yeast extract, 0.5% (w/v) Kraft lignin and 10 days of cultivation. The maximum laccase titer when assayed on DMP was 8.4 U/mL, following the conditions optimized: 1.125% yeast extract, 0.25% Kraft lignin and 7 days of cultivation. The analysis of cultures led to identification of metabolites; two being aromatic: 2,6-dimethoxy benzoic acid and sesamin; also, fumonisin and long-chain fatty acids. As a result of the study, the maximum laccase activities of 9.8 and 8.4 U/mL measured from ABTS and DMP substrates, respectively. The search shows new sources of fungal laccase for obtaining new metabolites of biodegradation from Kraft lignin in culture medium.
Clinical Proteomics, 2021
Glioblastoma (GBM) is a grade IV glioma highly aggressive and refractory to the therapeutic appro... more Glioblastoma (GBM) is a grade IV glioma highly aggressive and refractory to the therapeutic approaches currently in use. O-GlcNAcylation plays a key role for tumor aggressiveness and progression in different types of cancer; however, experimental evidence of its involvement in GBM are still lacking. Here, we show that O-GlcNAcylation plays a critical role in maintaining the composition of the GBM secretome, whereas inhibition of OGA activity disrupts the intercellular signaling via microvesicles. Using a label-free quantitative proteomics methodology, we identified 51 proteins in the GBM secretome whose abundance was significantly altered by activity inhibition of O-GlcNAcase (iOGA). Among these proteins, we observed that proteins related to proteasome activity and to regulation of immune response in the tumor microenvironment were consistently downregulated in GBM cells upon iOGA. While the proteins IGFBP3, IL-6 and HSPA5 were downregulated in GBM iOGA cells, the protein SQSTM1/p62...
Tuberculosis, 2021
Although treatable with antibiotics, tuberculosis is a leading cause of death. Mycobacterium tube... more Although treatable with antibiotics, tuberculosis is a leading cause of death. Mycobacterium tuberculosis antibiotic resistance is becoming increasingly common and disease control is challenging. Conventional drug susceptibility testing takes weeks to produce results, and treatment is often initiated empirically. Therefore, new methods to determine drug susceptibility profiles are urgent. Here, we used mass-spectrometry-based metabolomics to characterize the metabolic landscape of drug-susceptible (DS), multidrug-resistant (MDR) and extensively drugresistant (XDR) M. tuberculosis. Direct infusion mass spectrometry data showed that DS, MDR, and XDR strains have distinct metabolic profiles, which can be used to predict drug susceptibility and resistance. This was later confirmed by Ultra-High-Performance Liquid Chromatography and High-Resolution Mass Spectrometry, where we found that levels of ions presumptively identified as isoleucine, proline, hercynine, betaine, and pantothenic acid varied significantly between strains with different drug susceptibility profiles. We then confirmed the identification of proline and isoleucine and determined their absolute concentrations in bacterial extracts, and found significantly higher levels of these amino acids in DS strains, as compared to drug-resistant strains (combined MDR and XDR strains). Our results advance the current understanding of the effect of drug resistance on bacterial metabolism and open avenues for the detection of drug resistance biomarkers.
Frontiers in Oncology, 2020
Deleterious effects have been widely associated with chronic pesticide exposure, including cancer... more Deleterious effects have been widely associated with chronic pesticide exposure, including cancer development. In spite of several known consequences that pesticides can trigger in the human body, few is known regarding its impact on breast cancer women that are chronically exposed to such substances during agricultural work lifelong. In this context, the present study performed a high-throughput toxicoproteomic study in association with a bioinformatics-based design to explore new putative processes and pathways deregulated by chronic pesticide exposure in breast cancer patients. To reach this goal, we analyzed comparatively non-depleted plasma samples from exposed (n = 130) and non-occupationally exposed (n = 112) women diagnosed with breast cancer by using a label-free proteomic tool. The list of proteins differentially expressed was explored by bioinformatics and the main pathways and processes further investigated. The toxicoproteomic study revealed that women exposed to pesticides exhibited mainly downregulated events, linked to immune response, coagulation and estrogen-mediated events in relation to the unexposed ones. Further investigation shown that the identified deregulated processes and pathways correlated with significant distinct levels tumor necrosis factor alpha and interleukin 1 beta in the blood, and specific clinicopathological characteristics pointed out by bioinformatics analysis as adipose-trophic levels, menopause and intratumoral clots formation. Altogether, these findings reinforce pesticides as downregulators of several biological process and highlight that these compounds can be linked to poor prognosis in breast cancer.
International Journal of Sports Physiology and Performance, 2019
Purpose: High cardiorespiratory capacity is a key determinant of human performance and life expec... more Purpose: High cardiorespiratory capacity is a key determinant of human performance and life expectancy; however, the underlying mechanisms are not fully understood. The objective of this pilot study was to investigate biochemical signatures of endurance-performance athletes using high-resolution nontargeted metabolomics. Methods: Elite long-distance runners with similar training and anthropometrical records were studied. After athletes’ maximal oxygen consumption () was measured, they were divided into 2 groups: low (<65 mL·kg−1·min−1, n = 7) and high (>75 mL·kg−1·min−1, n = 7). Plasma was collected under basal conditions after 12 hours of fasting and after a maximal exercise test (nonfasted) and analyzed by high-resolution LC–MS. Multivariate and univariate statistics were applied. Results: A total of 167 compounds were putatively identified with an LC–MS-based metabolomics pipeline. Partial least-squares discriminant analysis showed a clear separation between groups. Signifi...
Environmental Toxicology, 2020
The zebrafish (Danio rerio) is a small teleost fish that is becoming increasingly popular in labo... more The zebrafish (Danio rerio) is a small teleost fish that is becoming increasingly popular in laboratories worldwide and several attributes have also placed the zebrafish under the spotlight of (eco)toxicological studies. Since the 1990s, international organizations such as ISO and OECD have published guidelines for the use of zebrafish in ecotoxicological assessment of environmental toxicants such as the Fish Embryo Acute Toxicity (FET) test, OECD n° 236 guideline. This protocol uses 3,4‐dichloroaniline (DCA), an aniline pesticide whose toxicity to fish species at early life stages is well known, as a positive control. Despite its use, little is known about its molecular mechanisms, especially in the context of the FET test. Therefore, this study aimed to investigate such changes in zebrafish larvae exposed to DCA (4 mg/L) for 96 hours using gel‐free proteomics. Twenty‐four proteins detected in both groups were identified as significantly affected by DCA exposure, and, when consider...
Metabolomics, 2019
Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder. HGPS children ... more Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder. HGPS children present a high incidence of cardiovascular complications along with altered metabolic processes and accelerated aging process. No metabolic biomarker is known and the mechanisms underlying premature aging are not fully understood. The present study analysed plasma from six HGPS patients of both sexes (7.7±1.4 years old; mean±SD) and eight controls (8.6±2.3 years old) by LC-MS/MS in high-resolution non-targeted metabolomics (Q-Exactive Plus). Several endogenous metabolites with statistical difference were found. Multivariate statistics analysis showed a clear separation between groups. Potential novel metabolic biomarkers are identified using the multivariate area under ROC curve (AUROC) based analysis, showing an AUC value higher than 0.80 using only two metabolites, and reaching 1.00 when increasing the number of metabolites in the AUROC model. Targeted metabolomics was used to validate some of the metabolites identified by the non-targeted method. Taken together, changed metabolic pathways in that panel involve sphingolipid, amino acid, and oxidation of fatty acids among others. In conclusion our data show significant alterations in cellular energy use and availability, in signal transduction, and in lipid metabolites, creating new insights on metabolic alterations associated with premature aging.
Drug testing and analysis, Jan 27, 2017
This paper summarizes the results obtained from the doping control analyses performed during the ... more This paper summarizes the results obtained from the doping control analyses performed during the Summer XXXI Olympic Games (from 03 to 21 August 2016) and XV Paralympic Games (from 07 to 18 September 2016). The analyses of all doping control samples were performed at the Brazilian Doping Control Laboratory (LBCD), a World Anti-Doping Agency (WADA)-accredited laboratory located in Rio de Janeiro, Brazil. A new facility at Rio de Janeiro Federal University (UFRJ) was built and fully operated by over seven hundred professionals, including Brazilian and international scientists, administrative staff and volunteers. For the Olympic Games, 4,913 samples were analysed. In 29 specimens, the presence of a prohibited substance was confirmed, resulting in adverse analytical findings (AAFs). For the Paralympic Games, 1,687 samples were analysed, twelve of which were reported as AAFs. For both events, 82.8% of the samples were urine, and 17.2% were blood samples. In total, more than thirty-one t...
Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder. HGPS children ... more Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder. HGPS children present a high incidence of cardiovascular complications along with altered metabolic processes and accelerated aging process. No metabolic biomarker is known and the mechanisms underlying premature aging are not fully understood. The present study analysed plasma from six HGPS patients of both sexes (7.7±1.4 years old; mean±SD) and eight controls (8.6±2.3 years old) by LC-MS/MS in high-resolution non-targeted metabolomics (Q-Exactive Plus). Several endogenous metabolites with statistical difference were found. Multivariate statistics analysis showed a clear separation between groups. Potential novel metabolic biomarkers are identified using the multivariate area under ROC curve (AUROC) based analysis, showing an AUC value higher than 0.80 using only two metabolites, and reaching 1.00 when increasing the number of metabolites in the AUROC model. Targeted metabolomics was used to validate...
Molecules
A sequential design strategy was applied to optimize the secretion of pectinases by a Saccharomyc... more A sequential design strategy was applied to optimize the secretion of pectinases by a Saccharomyces cerevisiae strain, from Brazilian sugarcane liquor vat, on passion fruit residue flour (PFRF), through solid-state fermentation (SSF). A factorial design was performed to determine the influence variables and two rotational central composite designs were executed. The validated experimental result was of 7.1 U mL−1 using 50% PFRF (w/w), pH 5, 30 °C for 24 h, under static SSF. Polygalacturonase, pectin methyl esterase, pectin–lyase and pectate–lyase activities were 3.5; 0.08; 3.1 and 0.8 U mL−1, respectively. Shotgun proteomics analysis of the crude extract enabled the identification of two pectin–lyases, one pectate–lyase and a glucosidase. The crude enzymatic extract maintained at least 80% of its original activity at pH values and temperatures ranging from 2 to 8 and 30 to 80 °C, respectively, over 60 min incubation. Results revealed that PFRF might be a cost-effective and eco-frien...
Ciência Rural, 2011
A promoção do crescimento vegetal pelos ácidos húmicos tem sido atribuída a ações similares a hor... more A promoção do crescimento vegetal pelos ácidos húmicos tem sido atribuída a ações similares a hormônios, devido à promoção do desenvolvimento e proliferação das raízes, resultando numa absorção mais eficiente de água e nutrientes. O objetivo deste trabalho foi analisar as mudanças na arquitetura radicular em plântulas de milho e no perfil de proteínas da membrana plasmática (MP) promovidas pelo tratamento com ácidos húmicos (AH) isolados de vermicomposto (20mg C L-1). O efeito da adição de ácido cítrico (AC), importante ácido orgânico presente nos exudados radiculares, sobre a bioatividade destes AH também foi investigada. Foram analisados o comprimento da raiz principal, o número de sítios de mitose, o número e comprimento de raízes laterais e a área radicular total. Para a análise do perfil protéico, vesículas da MP de células de raízes foram obtidas por fracionamento celular e as proteínas analisadas por eletroforese uni (1D) e bidimensional (2D). Observou-se que a adição de AC (...
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Papers by Joseph A. Medeiros Evaristo