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1.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360852

RESUMO

Fluoxetine is an antidepressant commonly prescribed not only to adults but also to children for the treatment of depression, obsessive-compulsive disorder, and neurodevelopmental disorders. The adverse effects of the long-term treatment reported in some patients, especially in younger individuals, call for a detailed investigation of molecular alterations induced by fluoxetine treatment. Two-year fluoxetine administration to juvenile macaques revealed effects on impulsivity, sleep, social interaction, and peripheral metabolites. Here, we built upon this work by assessing residual effects of fluoxetine administration on the expression of genes and abundance of lipids and polar metabolites in the prelimbic cortex of 10 treated and 11 control macaques representing two monoamine oxidase A (MAOA) genotypes. Analysis of 8871 mRNA transcripts, 3608 lipids, and 1829 polar metabolites revealed substantial alterations of the brain lipid content, including significant abundance changes of 106 lipid features, accompanied by subtle changes in gene expression. Lipid alterations in the drug-treated animals were most evident for polyunsaturated fatty acids (PUFAs). A decrease in PUFAs levels was observed in all quantified lipid classes excluding sphingolipids, which do not usually contain PUFAs, suggesting systemic changes in fatty acid metabolism. Furthermore, the residual effect of the drug on lipid abundances was more pronounced in macaques carrying the MAOA-L genotype, mirroring reported behavioral effects of the treatment. We speculate that a decrease in PUFAs may be associated with adverse effects in depressive patients and could potentially account for the variation in individual response to fluoxetine in young people.


Assuntos
Antidepressivos/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Fluoxetina/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Transtornos Mentais/tratamento farmacológico , Animais , Ácidos Graxos Insaturados/metabolismo , Macaca mulatta , Masculino
2.
BMC Genomics ; 22(1): 505, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225652

RESUMO

BACKGROUND: Sunflower is an important oilseed crop domesticated in North America approximately 4000 years ago. During the last century, oil content in sunflower was under strong selection. Further improvement of oil properties achieved by modulating its fatty acid composition is one of the main directions in modern oilseed crop breeding. RESULTS: We searched for the genetic basis of fatty acid content variation by genotyping 601 inbred sunflower lines and assessing their lipid and fatty acid composition. Our genome-wide association analysis based on the genotypes for 15,483 SNPs and the concentrations of 23 fatty acids, including minor fatty acids, revealed significant genetic associations for eleven of them. Identified genomic regions included the loci involved in rare fatty acids variation on chromosomes 3 and 14, explaining up to 34.5% of the total variation of docosanoic acid (22:0) in sunflower oil. CONCLUSIONS: This is the first large scale implementation of high-throughput lipidomic profiling to sunflower germplasm characterization. This study contributes to the genetic characterization of Russian sunflower collections, which made a substantial contribution to the development of sunflower as the oilseed crop worldwide, and provides new insights into the genetic control of oil composition that can be implemented in future studies.


Assuntos
Ácidos Graxos/análise , Helianthus , Óleos Vegetais/análise , Estudos de Associação Genética , Genótipo , Helianthus/genética , América do Norte , Melhoramento Vegetal , Federação Russa
3.
Biomolecules ; 11(5)2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064997

RESUMO

Schizophrenia is a serious mental disorder requiring lifelong treatment. While medications are available that are effective in treating some patients, individual treatment responses can vary, with some patients exhibiting resistance to one or multiple drugs. Currently, little is known about the causes of the difference in treatment response observed among individuals with schizophrenia, and satisfactory markers of poor response are not available for clinical practice. Here, we studied the changes in the levels of 322 blood plasma lipids between two time points assessed in 92 individuals diagnosed with schizophrenia during their inpatient treatment and their association with the extent of symptom improvement. We found 20 triglyceride species increased in individuals with the least improvement in Positive and Negative Syndrome Scale (PANSS) scores, but not in those with the largest reduction in PANSS scores. These triglyceride species were distinct from the rest of the triglyceride species present in blood plasma. They contained a relatively low number of carbons in their fatty acid residues and were relatively low in abundance compared to the principal triglyceride species of blood plasma.


Assuntos
Antipsicóticos/efeitos adversos , Sintomas Comportamentais/epidemiologia , Biomarcadores/sangue , Lipidômica/métodos , Esquizofrenia/tratamento farmacológico , Triglicerídeos/sangue , Adolescente , Adulto , Sintomas Comportamentais/sangue , Sintomas Comportamentais/induzido quimicamente , Sintomas Comportamentais/diagnóstico , Feminino , Humanos , Pacientes Internados/psicologia , Pacientes Internados/estatística & dados numéricos , Masculino , Federação Russa/epidemiologia , Esquizofrenia/patologia , Resultado do Tratamento , Adulto Jovem
4.
Elife ; 102021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33942714

RESUMO

We analyze the metabolomes of humans, chimpanzees, and macaques in muscle, kidney and three different regions of the brain. Although several compounds in amino acid metabolism occur at either higher or lower concentrations in humans than in the other primates, metabolites downstream of adenylosuccinate lyase, which catalyzes two reactions in purine synthesis, occur at lower concentrations in humans. This enzyme carries an amino acid substitution that is present in all humans today but absent in Neandertals. By introducing the modern human substitution into the genomes of mice, as well as the ancestral, Neandertal-like substitution into the genomes of human cells, we show that this amino acid substitution contributes to much or all of the reduction of de novo synthesis of purines in humans.

5.
Anal Chem ; 93(3): 1677-1685, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33373190

RESUMO

Mass spectrometry imaging (MSI) has become an important tool for 2D profiling of biological tissues, allowing for the visualization of individual compound distributions in the sample. Based on this information, it is possible to investigate the molecular organization within any particular tissue and detect abnormal regions (such as tumor regions) and many other biologically relevant phenomena. However, the large number of compounds present in the spectra hinders the productive analysis of large MSI datasets when utilizing standard tools. The heterogeneity of samples makes exploratory visualization (a presentation of the general idea of the molecular and structural organization of the inspected tissues) challenging. Here, we explore the application of various dimensionality reduction techniques that have been used extensively in the visualization of hyperspectral images and the MSI data specifically, such as principal component analysis, independent component analysis, non-negative matrix factorization, t-distributed stochastic neighbor embedding, and uniform manifold approximation and projection. Further, we propose a new approach based on a combination of structure preserving visualization with nonlinear manifold embedding of normalized spectral data. This way, we aim to preserve as much spatially overlapping signals as possible while augmenting them with information on compositional (spectral) variation. The proposed approach can be used for exploratory visualization of MSI datasets without prior deep chemical or histological knowledge of the sample. Thus, different datasets can be visually compared employing the proposed method. The proposed approach allowed for the clear visualization of the molecular layer, granular layer, and white matter in chimpanzee and macaque cerebellum slices.


Assuntos
Encéfalo/metabolismo , Algoritmos , Animais , Feminino , Macaca mulatta , Masculino , Espectrometria de Massas , Pan troglodytes , Análise de Componente Principal
6.
Commun Biol ; 2: 234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31263778

RESUMO

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with yet incompletely uncovered molecular determinants. Alterations in the abundance of low molecular weight compounds (metabolites) in ASD could add to our understanding of the disease. Indeed, such alterations take place in the urine, plasma and cerebellum of ASD individuals. In this work, we investigated mass-spectrometric signal intensities of 1,366 metabolites in the prefrontal cortex grey matter of 32 ASD and 40 control individuals. 15% of these metabolites showed significantly different intensities in ASD and clustered in 16 metabolic pathways. Of them, ten pathways were altered in urine and blood of ASD individuals (Fisher test, p < 0.05), opening an opportunity for the design of new diagnostic instruments. Furthermore, metabolic measurements conducted in 40 chimpanzees and 40 macaques showed an excess of metabolite intensity differences unique to humans, supporting the hypothesized disruption of evolutionary novel cortical mechanisms in ASD.


Assuntos
Transtorno Autístico/metabolismo , Metaboloma , Córtex Pré-Frontal/metabolismo , Animais , Evolução Molecular , Substância Cinzenta/metabolismo , Humanos , Macaca mulatta , Aprendizado de Máquina , Redes e Vias Metabólicas , Pan troglodytes
7.
J Chromatogr A ; 1574: 82-90, 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30217383

RESUMO

The lack of standard substances is a bottleneck for quality control in traditional and alternative medicine. Development of the HPLC-UV approaches combined with single standard for quantitative analysis of multi-component system (QAMS) allowed determination of several plant biomarkers by implementation of the relative response factors (RRFs). Robustness and ruggedness of such methods are commonly demonstrated by performing the analysis in changing analytical conditions on the different HPLC equipment and columns. The nature of MS detection is much more complicated and dependent on the instrumentation. Therefore, this study was conducted to justify the use of RRFs for HPLC-MS determination of bioactive compounds from plants. Protopanaxatriol (PPT), protopanaxadiol (PPD) and ocotillol (OT) ginseng saponins (ginsenosides) were successfully separated on a reversed-phase PFP-column with high group selectivity. Fragmentation patterns for these groups of compounds were established on different HPLC-ESI-MS systems and at varied declustering potentials (DPs). The use of sapogenin fragmentation ions in positive detection mode along with group reference standards was shown to be an optimal way to perform quantification. The performance of the developed group targeted HPLC-MS-QAMS approach was tested in the course of measurements conducted on the different instrumentation. The differences between QAMS and external standard method (ESM) quantification results were below 15% for all determined saponins.


Assuntos
Técnicas de Química Analítica/métodos , Ginsenosídeos/análise , Espectrometria de Massas , Plantas/química , Cromatografia Líquida de Alta Pressão , Ginsenosídeos/química , Ginsenosídeos/isolamento & purificação , Controle de Qualidade
8.
Biomed Chromatogr ; 32(12): e4363, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30110513

RESUMO

Evaluation of safety, quality and composition of herbal products and food supplements based on botanical ingredients is a matter of serious concern. For screening of botanicals in herbal products multitargeted and group-targeted approaches may be applied. In the group-targeted approach botanicals are characterized by means of an appropriate group of structurally related biomarkers compared with the multitargeted approach where a number of selected analytes are monitored based on a multiple reaction monitoring survey. In this study a unified strategy for quality control of herbal products was developed on the basis of fast ultrasound-assisted extraction, chromatographic separation and mass spectrometric quantification of bioactive compounds. A large list of unique biomarkers were monitored under almost identical chromatographic conditions, while an efficient strategy for HPLC-MS group-targeted analysis was also developed for comprehensive evaluation of chemical composition of botanicals intensively used for herbal product manufacturing. In the latter case, structurally close compounds were determined in a single ion monitoring mode for the characteristic group of fragment ions, allowing fast profiling and quality assessment of the plant material or complex food supplement. The sensitivity of the developed approaches was on the level of 1-50 ng/mL, which is higher than that of existing HPLC-UV quality control methods.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Compostos Fitoquímicos/análise , Preparações de Plantas/análise , Preparações de Plantas/normas , Limite de Detecção , Modelos Lineares , Preparações de Plantas/química , Controle de Qualidade , Reprodutibilidade dos Testes
9.
Nat Prod Res ; 32(20): 2490-2493, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29251993

RESUMO

The composition of ginseng oolong a widely used tea product was investigated. A new sweet-tasting cycloartane-type saponin 3ß-O-[ß-D-glucuronopyranosyl(1→2)]-ß-D-6-acetylglucopyranosyl)-(20S,22S)-3ß,22-dihydroxy-9,19-cyclolanost-24-en-26,29-oic acid (9), along with five new compounds, was identified in the methanolic extract of the ginseng oolong tea. Structural elucidation was conducted by spectroscopic methods, including 1D- and 2D-NMR, HR-MS, HPLC-LITMS/MS. It was shown that these compounds have different sugar chains connected to the abrusogenin molecule. Then saponin profiles of four commercially available ginseng oolong samples and Abrus precatorius L. leaves were compared and the presence of three known abrusosides and six new acetyl and malonyl abrusogenin derivatives was proved. The original ginsenosides were not detected in the extract, therefore, abrusosides could serve as a replacement responsible for the sweet taste of the tea.


Assuntos
Abrus/química , Panax/química , Saponinas/química , Chá/química , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Folhas de Planta/química , Saponinas/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificação
10.
J Pharm Biomed Anal ; 132: 87-92, 2017 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-27697574

RESUMO

Conventional liquid chromatographic methods coupled with ultraviolet detection with low-wavelength range are lacking selectivity and sensitivity to determine both polar and less polar ginsenosides. Also the lack of standard substances for such quality control methods is leading to development of the approaches using single standard for quantitative analysis of multi-component system (QAMS). The objective of present study was to establish and compare for the first time liquid chromatography-ultraviolet detection and liquid chromatography-mass spectrometry QAMS methods for the simultaneous determination of protopanaxatriol-type and protopanaxadiol-type ginsenosides in a variety of ginseng products. Sixteen polar and less polar ginsenosides were separated on a reversed-phase C18-column (150mm×2.0mm, 2.2µm) with a mobile phase consisting of 0.1% formic acid in water and acetonitrile. Components were then detected by means of ultraviolet and mass spectrometry detection. Characteristic sapogenin fragmentation signals with m/z 423 and 425 for two major groups of ginseng saponins allowed their simultaneous determination in a single chromatographic run, while the use of ultraviolet detection tends to give overvalued results. Structural correlation between the relative response factors and saponin structure was demonstrated. The method was linear (R2 >0.999) and sensitive (LODs, 0.01-0.03mg/mL) within the concentration range tested. Concentrations of individual ginsenosides and several quality control parameters were determined in ginseng root extracts and commercial ginseng products of different types (root slices, tablets and tea samples), and results showed that ginsenoside content can be successfully measured by means of QAMS approach.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Panax/química , Saponinas/análise , Acetonitrilas/química , Ginsenosídeos/análise , Íons , Limite de Detecção , Modelos Lineares , Extratos Vegetais/química , Raízes de Plantas/química , Controle de Qualidade , Valores de Referência , Reprodutibilidade dos Testes , Sapogeninas/análise , Sensibilidade e Especificidade , Raios Ultravioleta , Água/química
11.
Biomed Chromatogr ; 29(6): 853-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25355704

RESUMO

A rapid single-run analytical approach suitable to achieve a comprehensive characterization of ginsenosides - the main bioactive compounds present in plant materials from Panax species and ginseng-based products - was developed. The method is based on high-performance liquid chromatography coupled with electrospray positive ionization linear ion trap mass spectrometry (HPLC/ESI-LITMS). The main ions in the ESI-LITMS spectra were attributed to molecular adducts with sodium and potassium and fragments corresponding to cleavage of the glycosidic bonds. The simplicity of the approach allows laborious sample preparation and sophisticated spectral information-dependent acquisition to be avoided, and provides an opportunity for rapid screening. The method may replace existing HPLC-DAD profiling approaches. The results of this study indicate that HPLC/ESI-LITMS is applicable for quality control purposes on processed products and allows the rapid and direct identification of ginsenosides in crude plant extracts.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ginsenosídeos/análise , Panax/química , Preparações de Plantas/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes
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