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Obesity is an excessive adipose tissue accumulation that may have detrimental effects on health. Particularly, childhood obesity has become one of the main public health problems in the 21st century, since its prevalence has widely increased in recent years. Childhood obesity is intimately related to the development of several comorbidities such as nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, non-congenital cardiovascular disease, chronic inflammation and anemia, among others. Within this tangled interplay between these comorbidities and associated pathological conditions, obesity has been closely linked to important perturbations in iron metabolism. Iron is the second most abundant metal on Earth, but its bioavailability is hampered by its ability to form highly insoluble oxides, with iron deficiency being the most common nutritional disorder. Although every living organism requires iron, it may also cause toxic oxygen damage by generating oxygen free radicals through the Fenton reaction. Thus, iron homeostasis and metabolism must be tightly regulated in humans at every level (i.e., absorption, storage, transport, recycling). Dysregulation of any step involved in iron metabolism may lead to iron deficiencies and, eventually, to the anemic state related to obesity. In this review article, we summarize the existent evidence on the role of the most recently described components of iron metabolism and their alterations in obesity.

The incidence of childhood obesity and metabolic syndrome has grown notably in the last years, becoming major public health burdens in developed countries. Nowadays, oxidative stress is well-recognized to be closely associated with the onset and progression of several obesity-related complications within the framework of a complex crosstalk involving other intertwined pathogenic events, such as inflammation, insulin disturbances, and dyslipidemia. Thus, understanding the molecular basis behind these oxidative dysregulations could provide new approaches for the diagnosis, prevention, and treatment of childhood obesity and associated disorders. In this respect, the transcriptomic characterization of miRNAs bares great potential because of their involvement in post-transcriptional modulation of genetic expression. Herein, we provide a comprehensive literature revision gathering state-of-the-art research into the association between childhood obesity, metabolic syndrome, and miRNAs. We put special emphasis on the potential role of miRNAs in modulating obesity-related pathogenic events, with particular focus on oxidative stress.

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.

Edible sprouts with germinating seeds of a few days of age are naturally rich in nutrients and other bioactive compounds. Among them, the cruciferous (Brassicaceae) sprouts stand out due to their high contents of glucosinolates (GLSs) and phenolic compounds. In order to obtain sprouts enriched in these phytochemicals, elicitation is being increasing used as a sustainable practice. Besides, the evidence regarding the bioavailability and the biological activity of these compounds after their dietary intake has also attracted growing interest in recent years, supporting the intake of the natural food instead of enriched ingredients or extracts. Also, there is a growing interest regarding their uses, consumption, and applications for health and wellbeing, in different industrial sectors. In this context, the present review aims to compile and update the available knowledge on the fundamental aspects of production, enrichment in composition, and the benefits upon consumption of diverse edible cruciferous sprouts, which are sources of phenolic compounds and glucosinolates, as well as the evidence on their biological actions in diverse pathophysiological situations and the molecular pathways involved.

Lipophenols, combining phenolic and lipid characteristics in an amphiphilic molecule, offer unique bioactive properties with therapeutic potential, including anti-inflammatory and anti-oxidant effects. Thus, palmitoyl-epigallocatechin gallate (PEGCG), a lipophilic derivative of the extensively studied (poly)phenol epigallocatechin gallate (EGCG), has been stressed concerning enhanced stability in lipid-rich environments and bioavailability due to improved cellular uptake. Nonetheless, the effect of lipophilic esterification on some cellular processes, particularly at the mitochondrial level, remains underexplored. According to this knowledge gap, the present study uncovered the cytotoxic and mitochondrial effects of PEGCG, in vitro, upon the liver hepatocarcinoma cell line HepG2. The range of determinations developed, including the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay, flow cytometry, and electron microscopy, allowed describing the distinct biological potential for both EGCG and PEGCG. Thus, while EGCG exhibited minimal cytotoxicity and apoptosis induction, PEGCG reduced cell viability dose-dependently at 24 h and triggered significant mitochondrial damage, including fragmentation and cristae loss, at 1 µmol/L. However, at 48 h, PEGCG-treated cells recovered viability and mitochondrial structure, suggesting the activation of adaptive mechanisms for the molecular changes induced by PEGCG. These findings underscore the dynamic interplay between lipophilic catechins and cellular stress responses, offering valuable insights into the PEGCG’s potential as a therapeutic agent and laying a foundation for further exploration of its biological power.

BackgroundMetabolomics is a powerful tool for investigating the association between nutrition and health status. Although urine is commonly employed for studying the metabolism and transformation of food components, the use of blood samples could be preferable to gain new insights into the bioavailability of diet-derived compounds and their involvement in health. However, the chemical complexity of blood samples hinders the analysis of this biological fluid considerably, which makes the development of novel and comprehensive analytical methods mandatory.MethodsIn this work, we optimized a multi-targeted metabolomics platform for the quantitative and simultaneous analysis of 450 food-derived metabolites by ultra-high performance liquid chromatography coupled to tandem mass spectrometry. To handle the chemical complexity of blood samples, three complementary extraction methods were assayed and compared in terms of recovery, sensitivity, precision and matrix effects with the aim of maximizing metabolomics coverage: protein precipitation, reversed solid-phase extraction, and hybrid protein precipitation with solid-phase extraction-mediated phospholipid removal.ResultsAfter careful optimization of the extraction conditions, protein precipitation enabled the most efficient and high-throughput extraction of the food metabolome in plasma, although solid-phase extraction-based protocols provided complementary performance for the analysis of specific polyphenol classes. The developed method yielded accurate recovery rates with negligible matrix effects, and good linearity, as well as high sensitivity and precision for most of the analyzed metabolites.ConclusionsThe multi-targeted metabolomics platform optimized in this work enables the simultaneous detection and quantitation of 450 dietary metabolites in short-run times using small volumes of biological sample, which facilitates its application to epidemiological studies.

The by-products of grapes (Vitis vinifera L.) in the winemaking process present a diverse phytochemical profile of (poly)phenols, essentially represented by phenolic acids, flavonoids, and stilbenes, which have health benefits. In winemaking, solid (grape stems and pomace) and semisolid (wine lees) by-products are generated, negatively impacting the sustainability of the agro-food activity and the local environment. Although information on the phytochemical profile of grape stems and pomace has been reported, especially information concerning (poly)phenols, research on wine lees is necessary to take advantage of the compositional traits of this residue. So, in the present work, an updated, in-depth comparison of the (poly)phenolic profiles of these three resulting matrices in the agro-food industry has been carried out to provide new knowledge and interesting data on the action of yeast and lactic acid bacteria (LAB) metabolism in the diversification of phenolic composition; additionally, we extract complementarities for the possible joint application of the three residues. The phytochemical analysis of the extracts was carried out using HPLC-PDA-ESI-MSn. The (poly)phenolic profiles of the residues showed significant discrepancies. The results obtained showed that the greatest diversity of (poly)phenols was found in the stems of the grapes, followed closely by the lees. Through technological insights, it has been suggested that yeasts and LAB, responsible for the fermentation of must, might play a key role in the transformation of phenolic compounds. This would provide new molecules with specific bioavailability and bioactivity features, which might interact with different molecular targets and, consequently, improve the biological potential of these underexploited residues.

The increased presence of bacteria in blood is a plausible contributing factor in the development and progression of aging-associated diseases. In this context, we performed the quantification and the taxonomic profiling of the bacterial DNA in blood samples collected from forty-three older subjects enrolled in a nursing home. Quantitative PCR targeting the 16S rRNA gene revealed that all samples contained detectable amounts of bacterial DNA with a concentration that varied considerably between subjects. Correlation analyses revealed that the bacterial DNAemia (expressed as concentration of 16S rRNA gene copies in blood) significantly associated with the serum levels of zonulin, a marker of intestinal permeability. This result was confirmed by the analysis of a second set of blood samples collected from the same subjects. 16S rRNA gene profiling revealed that most of the bacterial DNA detected in blood was ascribable to the phylum Proteobacteria with a predominance of the genus Pseudomonas. Several control samples were also analyzed to assess the influence of contaminant bacterial DNA potentially originating from reagents and materials. The data reported here suggest that para-cellular permeability of epithelial (and, potentially, endothelial) cell layers may play an important role in bacterial migration into the bloodstream. Bacterial DNAemia is likely to impact on several aspects of host physiology and could underpin the development and prognosis of various diseases in older subjects.

The residues generated in the wine industry (pomace, stems, seeds, wine lees, and grapevine shoots) are a potential source of bioactive compounds that can be used in other industries despite being sometimes underestimated. Different extraction methods using various solvents and extraction conditions are currently being investigated. Due to its natural occurrence in wines, safe behavior, and low toxicity when compared to other organic solvents, ethanol is used as an extracting agent. The aim of this study was to identify the winery by-product from the Região Demarcada do Douro and its corresponding extraction solvents that yields the most favorable results in (poly)phenols content and antioxidant capacity. To achieve this, five different ratios of ethanol: water, namely 0:100, 25:75, 50:50, 75:25, and 100:0 (v/v), for extracting the phenolic compounds were employed. Afterwards, the determination of total phenolic content (TPC), ortho-diphenols content (ODC), and flavonoid content (FC) as well as the antioxidant capacity of the obtained extracts using three different methods was performed. Since the best results of the spectrophotometric assays were obtained mostly with hydroethanolic extracts of stems (50:50, v/v), identification by HPLC-DAD has carried out. It was possible to conclude that the Tinta Roriz variety displayed the highest number of identified (poly)phenols.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with heterogeneous clinical progression, reflecting distinct underlying pathological mechanisms. Early and accurate diagnosis and prognosis require reliable biomarkers to improve clinical management and therapeutic stratification. The present study explores the potential of platelet global metabolomics and fatty acid (FA) profiling as potential sources of diagnostic and prognostic biomarkers for ALS. We analysed platelets from 15 recently diagnosed ALS patients and 21 healthy controls (CTLs) using liquid chromatography-mass spectrometry (LC–MS) for metabolomics and gas chromatography-flame ionization detection (GC-FID) for FA profiling. ALS patients were classified as fast or slow progressors based on the median ALS Functional Rating Scale-Revised (ALSFRS-R) slope. While global metabolomic and FA profiles have shown limited potential for distinguishing ALS from CTL, preliminary molecular annotation based on mass and retention times disclosed specific metabolites with potential diagnostic value. Importantly, both global metabolomic and FA analyses demonstrated a marked capacity to differentiate fast progressors from slow progressors (receiver operating characteristic (ROC) curves of approximately 1), revealing distinct metabolic signatures associated with disease progression. Our findings demonstrate that platelet global metabolomics and FA profiling hold promise as prognostic biomarkers in ALS.