451 research outputs found
Food Authentication: Techniques, Trends and Emerging Approaches
Multiple factors can directly influence the chemical composition of foods and, consequently, their organoleptic, nutritional, and bioactive properties, including their geographical origin, the variety or breed, as well as the conditions of cultivation, breeding, and/or feeding, among others. Therefore, there is a great interest in the development of accurate, robust, and high-throughput analytical methods to guarantee the authenticity and traceability of foods. For these purposes, a large number of sensorial, physical, and chemical approaches can be used, which must be normally combined with advanced statistical tools. In this vein, the aim of the Special Issue “Food Authentication: Techniques, Trends, and Emerging Approaches” is to gather original research papers and review articles focused on the development and application of analytical techniques and emerging approaches in food authentication. This Special Issue comprises 12 valuable scientific contributions, including one review article and 11 original research works, dealing with the authentication of foods with great commercial value, such as olive oil, Iberian ham, and fruits, among others
Desarrollo de métodos analíticos metabolómicos y metalómicos para el estudio de la enfermedad de Alzheimer : diseño de nuevos biomarcadores químicos de diagnosis
La enfermedad de Alzheimer (EA) es el trastorno neurodegenerativo más común entre la población de edad avanzada, el cual se caracteriza por un inicio insidioso y un declive progresivo de las funciones cognitivas, En la actualidad no existe una cura para esta enfermedad en gran parte debido a que su etiología es aún desconocida, aunque existe la creciente evidencia de que pueden intervenir múltiples procesos patológicos, donde confluyen factores tanto genéticos como ambientales, o propios del envejecimiento. Además, las actuales pruebas de diagnóstico de la EA muestran grandes limitaciones, incluyendo una baja sensibilidad y especificidad, así como la imposibilidad de detectar de forma precoz la sintomatologia característica de esta enfermedad. Por todo ello, la identificación de nuevos biomarcadores diagnósticos es de vital importancia.
El objetivo principal de esta Tesis fue la optimización de procedimientos metaboiómicos y metalómicos, y su posterior aplicación en el estudio de la etiología de la enfermedad de Alzheimer y el descubrimiento de potenciales biomarcadores de diagnóstico. Los métodos analíticos desarrollados en los trabajos que componen esta Tesis se basan en el empleo de la espectrometría de masas como técnica de detección, debido a su amplio rango de apíicabilidad, sensibilidad y especificidad. Con el fin de conseguii- una cobertura metabolómíca integral se optimizaron múltiples plataformas analíticas complementarias, incluyendo procedimientos de análisis directo mediante espectrometría de masas (DI-ESI-MS, FIA-APPI- MS) y su acoplamiento con distintas técnicas de separación ortogonales (UHPLC-MS, GC-MS, CE-MS). Las plataformas de análisis directo mostraron un gran potencial para realizar un primer screening metabòlico de múltiples fluidos y tejidos biológicos, gracias a su reducido tiempo de análisis y simplicidad instrumental. Posteriormente, las técnicas acopladas permitieron llevar a cabo una investigación más exhaustiva de la totalidad del metaboloma mediante el empleo de mecanismos de retención complementarios. Alternativamente, también se desarrolló un procedimiento metalómico basado en el fraccionamiento de metalo-especies según su peso molecular mediante precipitación de proteínas en condiciones no desnaturalizantes y posterior análisis en ICP-MS.
La aplicación de estas técnicas metabolómicas y metalómicas en muestras de suero sanguíneo de pacientes afectados por la enfermedad de Alzheimer y deterioro cognitivo leve permitió identificar numerosos mecanismos patológicos relacionados con la patogénesis de esta enfermedad y su progresión desde etapas pre-clínicas. Así, algunos de los hallazgos más importantes de este estudio fue la detección de alteraciones significativas en la composición de lípidos de membrana, déficits en el metabolismo energético y sistemas de neurotransmisión, hiperamonemia, hiperiipidemia, estrés oxidativo, o una homeostasis alterada de múltiples elementos metálicos y metaloides, entre otros. A su vez, estas perturbaciones metabólicas también fueron observadas en múltiples compartimentos biológicos del modelo APPswe/PSÍAE9, incluyendo suero, cerebro, hígado, riñón, bazo y timo, evidenciando así la utilidad de este ratón transgénico para modelar la EA. La comparación de distintas regiones cerebrales demostró que las áreas más afectadas por la neuropatologia característica de esta enfermedad son el hipocampo y la corteza cerebral, aunque otras regiones también se vieron perturbadas en menor medida, incluyendo el estriado, cerebelo y bulbos olfatorios. Además, las alteraciones detectadas en los órganos periféricos (i.e. hígado, rifíón, bazo y timo) confirman la naturaleza sistèmica de este trastorno neurodegenerativo. Por último, se desarrolló un nuevo modelo de función inmune deteriorada basado en la depleción del gen de la interleucina-4 en APP/PS1 (APP/PS1/IL4-KO) con el objetivo de investigar los mecanismos subyacentes a la componente inflamatoria de la EA. Así, la aplicación de técnicas metabolómicas reveló alteraciones en la biosíntesis de histamina, el metabolismo de aminoácidos, producción de eicosanoides y fallos en el ciclo de la urea.
De este modo, se puede concluir que la aplicación combinada de múltiples técnicas metabolómicas y metalómicas en distintas matrices biológicas, tanto de pacientes humanos como animales modelo, permite estudiar en profundidad la etiología asociada a la enfermedad de Alzheimer, y descubrir así posibles biomarcadores de diagnosis.Alzheimer’s disease (AD) is the most common neurodegenerative disorder among older people, which is characterized by an insidious onset and progressive decline of cognitive functions. Nowadays there is no cure for this disease principally because its etiology is still unknown, although there is growing evidence that multiple pathological processes may be involved, with the confluence of genetic, environmental and aging-related factors. Furthermore, current diagnostic tests for AD show great limitations, including low sensitivity and specificity as well as the impossibility of early detection of the characteristic symptoms of this disease. Therefore, the identification of new biomarkers for diagnosis is critical.
The main objective of this Thesis was the optimization of metabolomic and metallomic approaches, and subsequent application for studying the etiology of Alzheimer's disease and the discovery of potential diagnostic biomarkers. Analytical methods developed in works comprised in this Thesis are based on the use of mass spectrometry as detection technique, due to its wide range of applicability, sensitivity and specificity. In order to get a comprehensive metabolomic coverage we optimized multiple complementary analytical platforms, including procedures for direct analysis by mass spectrometry (DI- ESI-MS, FIA-APPI-MS) and its coupling with orthogonal separation techniques (UHPLC-MS, GC-MS, CE-MS). Direct analysis platforms showed a great potential to perform a first metabolic screening in multiple biological fluids and tissues, due to its reduced analysis time and instrumental simplicity. Subsequently, coupled techniques allowed carrying out a more comprehensive investigation of the whole metabolome by using complementary mechanisms of retention. Alternatively, we also developed a metallomic procedure based on the fractionation of metallo-species according to their molecular weight by means of protein precipitation in non-denaturing conditions and subsequent ICP-MS analysis.
The application of these metabolomic and metallomic techniques in serum samples from patients with Alzheimer's disease and mild cognitive impairment allowed the identification of numerous pathological mechanisms related to the pathogenesis of this disorder and its progression from pre-clinical stages. Thus, some of the most important findings of this study were the detection of significant changes in the composition of membrane lipids, deficits in energy metabolism and neurotransmitter systems, oxidative stress, hyperammonemia, hyperlipidemia, or an altered homeostasis of multiple metallic and metalloid elements, among others. In turn, these metabolic disturbances were also observed in multiple biological compartments from the APPswe/PSlAE9 model, including serum, brain, liver, kidney, spleen and thymus, thus demonstrating the utility of this transgenic mouse for modelling AD. The comparison of different brain regions showed that the areas most affected by the characteristic neuropathology of this disease were hippocampus and cortex, although other regions were also disrupted to a lesser extent, including the striatum, cerebellum and olfactory bulbs. Furthermore, alterations detected in peripheral organs (i.e. liver, kidney, spleen and thymus) confirm the systemic nature of this neurodegenerative disorder. Finally, a new model of impaired immune function was developed based on the depletion of interleukin-4 gen in APP/PS1 (APP/PS1/TL4-KO) in order to investigate mechanisms underlying to the inflammatory component of AD. Thus, the application of metabolomic techniques revealed alterations in the biosynthesis of histamine, amino acid metabolism, production of eicosanoids and failures in the urea cycle.
Therefore, it can be concluded that the combined application of multiple metabolomic and metallomic approaches in different biological matrices, from both human patients and animal models, allows to study in depth the etiology associated with Alzheimer's disease, and discover potential biomarkers of diagnosis
Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity
Background: Trace elements and heavy metals have proven pivotal roles in childhood obesity and insulin resistance. However, growing evidence suggests that insulin resistance could encompass distinct phenotypic subtypes. Methods: Herein, we performed a comprehensive metallomics characterization of plasma samples from children and adolescents with obesity and concomitant insulin resistance, who were stratified as early (N = 17, 11.4 ± 2.4 years), middle (N = 16, 11.8 ± 1.9 years), and late (N = 33, 11.7 ± 2.0 years) responders according to the insulin secretion profile in response to an oral glucose tolerance test. To this end, we employed a high-throughput method aimed at determining the biodistribution of various essential and toxic elements by analyzing total metal contents, metal-containing proteins, and labile metal species. Results: Compared with the early responders, participants with delayed glucose-induced hyperinsulinemia showed a worsened insulin resistance (HOMA-IR, 4.5 vs. 3.8) and lipid profile (total cholesterol, 160 vs. 144 mg/dL; LDL-cholesterol, 99 vs. 82 mg/dL), which in turn was accompanied by sharpened disturbances in the levels of plasmatic proteins containing chromium (4.8 vs. 5.1 µg/L), cobalt (0.79 vs. 1.2 µg/L), lead (0.021 vs. 0.025 µg/L), and arsenic (0.077 vs. 0.17 µg/L). A correlation analysis demonstrated a close inter-relationship among these multielemental perturbations and the characteristic metabolic complications occurring in childhood obesity, namely impaired insulin-mediated metabolism of carbohydrates and lipids. Conclusions: These findings highlight the crucial involvement that altered metal homeostasis and exposure may have in regulating insulin signaling, glucose metabolism, and dyslipidemia in childhood obesity.This research was funded by the Spanish Government through Instituto de Salud Carlos III (PI22/01899). AGD is supported by an intramural grant from the Biomedical Research and Innovation Institute of Cádiz (LII19/16IN-CO24), and RGD is a recipient of a “Miguel Servet” fellowship (CP21/00120) funded by Instituto de Salud Carlos III
Assessment of Virgin Olive Oil Adulteration by a Rapid Luminescent Method
The adulteration of virgin olive oil with hazelnut oil is a common fraud in the food industry,
which makes mandatory the development of accurate methods to guarantee the authenticity and
traceability of virgin olive oil. In this work, we demonstrate the potential of a rapid luminescent
method to characterize edible oils and to detect adulterations among them. A regression model
based on five luminescent frequencies related to minor oil components was designed and validated,
providing excellent performance for the detection of virgin olive oil adulteration
Exploring the association between circulating trace elements, metabolic risk factors, and the adherence to a Mediterranean diet among children and adolescents with obesity
Diet is one of the most important modifiable lifestyle factors for preventing and
treating obesity. In this respect, the Mediterranean diet (MD) has proven to be a
rich source of a myriad of micronutrients with positive repercussions on human
health. Herein, we studied an observational cohort of children and adolescents with
obesity (N = 26) to explore the association between circulating blood trace elements
and the degree of MD adherence, as assessed through the KIDMED questionnaire.
Participants with higher MD adherence showed better glycemic/insulinemic control
and a healthier lipid profile, as well as raised plasma levels of selenium, zinc,
cobalt, molybdenum, and arsenic, and increased erythroid content of selenium.
Interestingly, we found that these MD-related mineral alterations were closely
correlated with the characteristic metabolic complications behind childhood obesity,
namely hyperglycemia, hyperinsulinemia, and dyslipidemia (p 0.35).
These findings highlight the pivotal role that dietary trace elements may play in the
pathogenesis of obesity and related disorders.This research was partially funded by the Spanish Government through Instituto de Salud Carlos III- (PI22/01899). ÁG-D
was supported by an intramural grant from the Biomedical Research and Innovation Institute of Cádiz (LII19/16INCO24),
and RG-D was recipient of a “Miguel Servet” fellowship (CP21/00120) funded by Instituto de Salud Carlos III
Sexually dimorphic metal alterations in childhood obesity are modulated by a complex interplay between inflammation, insulin, and sex hormones
Although growing evidence points to a pivotal role of perturbed metal homeostasis
in childhood obesity, sexual dimorphisms in this association have rarely
been investigated. In this study, we applied multi-elemental analysis to plasma
and erythrocyte samples from an observational cohort comprising children
with obesity, with and without insulin resistance, and healthy control children.
Furthermore, a wide number of variables related to carbohydrate and lipid
metabolism, inflammation, and sex hormones were also determined. Children
with obesity, regardless of sex and insulin resistance status, showed increased
plasma copper-to-zinc ratios. More interestingly, obesity-related erythroid
alterations were found to be sex-dependent, with increased contents of iron,
zinc, and copper being exclusively detected among female subjects. Our findings
suggest that a sexually dimorphic hormonal dysregulation in response to
a pathological cascade involving inflammatory processes and hyperinsulinemia
could be the main trigger of this female-specific intracellular sequestration of
trace elements. Therefore, the present study highlights the relevance of genotypic
sex as a susceptibility factor influencing the pathogenic events behind
childhood obesity, thereby opening the door to develop sex-personalized
approaches in the context of precision medicine.INiBICA, Grant/Award Number: LII19/16IN-CO24; Instituto de Salud Carlos III, Grant/Award Numbers: CP21/00120, PI22/0189
Metabolomics in Alzheimer's disease: The need of complementary analytical platforms for the identification of biomarkers to unravel the underlying pathology
Alzheimer's disease is a complex neurodegenerative disorder characterized by a multi-factorial etiology, not completely understood to date. In this context, the application of metabolomics is emerging in the last years because of its potential to monitor molecular alterations associated with disease pathogenesis and progression, as well as to discover candidate diagnostic biomarkers. However, the huge heterogeneity and dynamism of the human metabolome makes impossible the simultaneous determination of the entire set of metabolites from complex biological samples. Thus, the most common strategy to get a comprehensive overview of the organism's phenotypic expression is the combined use of complementary metabolomic platforms. In this review, we summarize the advantages and limitations of the most important analytical techniques usually employed in metabolomics, including nuclear magnetic resonance, direct infusion mass spectrometry and hyphenated approaches based on the coupling of orthogonal separation mechanisms (i.e. liquid chromatography, gas chromatography, capillary electrophoresis) with mass spectrometry. Moreover, the suitability of metabolomics to unravel the complex pathology underlying to Alzheimer's disease is also presented. (C) 2017 Elsevier B.V. All rights reserved
Mechanistic Insights into Alzheimer’s Disease Unveiled through the Investigation of Disturbances in Central Metabolites and Metabolic Pathways
Hydrophilic metabolites are closely involved in multiple primary metabolic pathways and, consequently, play an essential role in the onset and progression of multifactorial human disorders, such as Alzheimer's disease. This review article provides a comprehensive revision of the literature published on the use of mass spectrometry-based metabolomics platforms for approaching the central metabolome in Alzheimer's disease research, including direct mass spectrometry, gas chromatography-mass spectrometry, hydrophilic interaction liquid chromatography-mass spectrometry, and capillary electrophoresis-mass spectrometry. Overall, mounting evidence points to profound disturbances that affect a multitude of central metabolic pathways, such as the energy-related metabolism, the urea cycle, the homeostasis of amino acids, fatty acids and nucleotides, neurotransmission, and others
Altered Metal Homeostasis Associates with Inflammation, Oxidative Stress, Impaired Glucose Metabolism, and Dyslipidemia in the Crosstalk between Childhood Obesity and Insulin Resistance
Metals are redox-active substances that participate in central biological processes and may be
involved in a multitude of pathogenic events. However, considering the inconsistencies reported in the
literature, further research is crucial to disentangle the role of metal homeostasis in childhood obesity
and comorbidities using well-characterized cohorts and state-of-the-art analytical methods. To this end,
we studied an observational population comprising childrenwith obesity and insulin resistance, children
with obesity without insulin resistance, and healthy control children. A multi-elemental approach based
on the size-fractionation of metal species was applied to quantify the total content of various essential
and toxic elements in plasma and erythrocyte samples, and to simultaneously investigate the metal
fractions conforming the metalloproteome and the labile metal pool. The most important disturbances
in childhood obesity were found to be related to elevated circulating copper levels, decreased content of
plasmatic proteins containing chromium, cobalt, iron, manganese, molybdenum, selenium, and zinc, as
well as the sequestration of copper, iron, and selenium within erythrocytes. Interestingly, these metal
disturbances were normally exacerbated among children with concomitant insulin resistance, and in
turn were associated to other characteristic pathogenic events, such as inflammation, oxidative stress,
abnormal glucose metabolism, and dyslipidemia. Therefore, this study represents one-step further
towards a better understanding of the involvement of metals in the crosstalk between childhood obesity
and insulin resistance.This research was partially funded by the Spanish Government through Instituto de
Salud Carlos III (CP21/00120, PI18/01316). Á.G.-D. is supported by an intramural grant from the
Biomedical Research and Innovation Institute of Cádiz (LII19/16IN-CO24), and R.G.-D. is recipient
of a “Miguel Servet” fellowship (CP21/00120) funded by Instituto de Salud Carlos III
Trace elements as potential modulators of puberty-induced amelioration of oxidative stress and inflammation in childhood obesity
Although puberty is known to influence obesity progression, the molecular
mechanisms underlying the role of sexual maturation in obesity-related complications
remains largely unexplored. Here, we delve into the impact of
puberty on the most relevant pathogenic hallmarks of obesity, namely oxidative
stress and inflammation, and their association with trace element blood
status. To this end, we studied a well-characterized observational cohort comprising
prepubertal (N = 46) and pubertal (N = 48) children with obesity.
From all participants, plasma and erythrocyte samples were collected and subjected
to metallomics analysis and determination of classical biomarkers of
oxidative stress and inflammation. Besides the expected raise of sexual hormones,
pubertal children displayed better inflammatory and oxidative control,
as reflected by lower levels of C-reactive protein and oxidative damage
markers, as well as improved antioxidant defense. This was in turn accompanied
by a healthier multielemental profile, with increased levels of essential
elements involved in the antioxidant system and metabolic control (metalloproteins
containing zinc, molybdenum, selenium, and manganese) and
decreased content of potentially deleterious species (total copper, labile free
iron). Therefore, our findings suggest that children with obesity have an exacerbated
inflammatory and oxidative damage at early ages, which could be ameliorated
during pubertal development by the action of trace element-mediated
buffering mechanisms.This research was funded by the Spanish Government through Instituto de Salud Carlos III (PI22/01899, PI18/01316). Állvaro González-Domínguez is supported by an intramural grant from the Biomedical Research and Innovation Institute of Cádiz (LII19/16IN-CO24), and Raúl González-Domínguez is recipient of a “Miguel Servet” fellowship funded by Instituto de Salud Carlos III (CP21/00120)
- …