RESUMEN
Transition-metal-catalyzed bioorthogonal reactions emerged a decade ago as a novel strategy to implement spatiotemporal control over enzymatic functions and pharmacological interventions. The use of this methodology in experimental therapy is driven by the ambition of improving the tolerability and PK properties of clinically-used therapeutic agents. The preclinical potential of bioorthogonal catalysis has been validated inâ vitro and inâ vivo with the inâ situ generation of a broad range of drugs, including cytotoxic agents, anti-inflammatory drugs and anxiolytics. In this article, we report our investigations towards the preparation of solid-supported Cu(I)-microdevices and their application in bioorthogonal uncaging and click reactions. A range of ligand-functionalized polymeric devices and off-on Cu(I)-sensitive sensors were developed and tested under conditions compatible with life. Last, we present a preliminary exploration of their use for the synthesis of PROTACs through CuAAC assembly of two heterofunctional mating units.
Asunto(s)
Química Clic , Cobre , Cobre/química , Catálisis , Materiales Biocompatibles/química , Alquinos/química , Ligandos , Polímeros/química , Humanos , Azidas/químicaRESUMEN
Bioorthogonal metallocatalysis has opened up a xenobiotic route to perform nonenzymatic catalytic transformations in living settings. Despite their promising features, most metals are deactivated inside cells by a myriad of reactive biomolecules, including biogenic thiols, thereby limiting the catalytic functioning of these abiotic reagents. Here we report the development of cytocompatible alloyed AuPd nanoparticles with the capacity to elicit bioorthogonal depropargylations with high efficiency in biological media. We also show that the intracellular catalytic performance of these nanoalloys is significantly enhanced by protecting them following two different encapsulation methods. Encapsulation in mesoporous silica nanorods resulted in augmented catalyst reactivity, whereas the use of a biodegradable PLGA matrix increased nanoalloy delivery across the cell membrane. The functional potential of encapsulated AuPd was demonstrated by releasing the potent chemotherapy drug paclitaxel inside cancer cells. Nanoalloy encapsulation provides a novel methodology to develop nanoreactors capable of mediating new-to-life reactions in cells.
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Nanotubos , Paladio , Aleaciones , Paclitaxel , CatálisisRESUMEN
Being recognized as the best-tolerated of all metals, the catalytic potential of gold (Au) has thus far been hindered by the ubiquitous presence of thiols in organisms. Herein we report the development of a truly-catalytic Au-polymer composite by assembling ultrasmall Au-nanoparticles at the protein-repelling outer layer of a co-polymer scaffold via electrostatic loading. Illustrating the in vivo-compatibility of the novel catalysts, we show their capacity to uncage the anxiolytic agent fluoxetine at the central nervous system (CNS) of developing zebrafish, influencing their swim pattern. This bioorthogonal strategy has enabled -for the first time- modification of cognitive activity by releasing a neuroactive agent directly in the brain of an animal.
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Ansiolíticos/metabolismo , Materiales Biocompatibles/metabolismo , Sistema Nervioso Central/metabolismo , Oro/metabolismo , Animales , Ansiolíticos/química , Materiales Biocompatibles/química , Catálisis , Sistema Nervioso Central/química , Oro/química , Estructura Molecular , Tamaño de la Partícula , Pez CebraRESUMEN
The search for novel targeted inhibitors active on glioblastoma multiforme is crucial to develop new treatments for this unmet clinical need. Herein, we report the results from a screening campaign against glioma cell lines using a proprietary library of 100 structurally-related pyrazolopyrimidines. Data analysis identified a family of compounds featuring a 2-amino-1,3-benzoxazole moiety (eCF309 to eCF334) for their antiproliferative properties in the nM range. These results were validated in patient-derived glioma cells. Available kinase inhibition profile pointed to blockade of the PI3K/mTOR pathway as being responsible for the potent activity of the hits. Combination studies demonstrated synergistic activity by inhibiting both PI3Ks and mTOR with selective inhibitors. Based on the structure activity relationships identified in this study, five new derivatives were synthesized and tested, which exhibited potent activity against glioma cells but not superior to the dual PI3K/mTOR inhibitor and lead compound of the screening eCF324.
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Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/química , Pirazoles/química , Pirimidinas/química , Serina-Treonina Quinasas TOR/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Glioma/metabolismo , Glioma/patología , Humanos , Fosfatidilinositol 3-Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Pirazoles/farmacología , Pirimidinas/farmacología , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad , Serina-Treonina Quinasas TOR/antagonistas & inhibidoresRESUMEN
Chemical proteomics approaches are widely used to identify molecular targets of existing or novel drugs. This manuscript describes the development of a straightforward approach to conjugate azide-labeled drugs via click chemistry to alkyne-tagged cell-penetrating fluorescent nanoparticles as a novel tool to study target engagement and/or identification inside living cells. A modification of the Baeyer test for alkynes allows monitoring the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, guaranteeing the presence of the drug on the solid support. As a proof of concept, the conjugation of the promiscuous kinase inhibitor dasatinib to Cy5-labeled nanoparticles is presented. Dasatinib-decorated fluorescent nanoparticles efficiently inhibited its protein target SRC in vitro, entered cancer cells, and colocalized with SRC in cellulo.
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Permeabilidad de la Membrana Celular , Colorantes Fluorescentes/química , Nanopartículas/química , Proteómica , Azidas/química , Catálisis , Química Clic , Reacción de Cicloadición , Dasatinib/química , HumanosRESUMEN
Lung cancer is the leading cause of cancer death in both men and women. It represents a public health problem that must be addressed through the early detection of specific biomarkers and effective treatment. To address this critical issue, it is imperative to implement effective methodologies for specific biomarker detection of lung cancer in real clinical samples. Electrochemical methods, including microfluidic devices and biosensors, can obtain robust results that reduce time, cost, and assay complexity. This comprehensive review will explore specific studies, methodologies, and detection limits and contribute to the depth of the discussion, making it a valuable resource for researchers and clinicians interested in lung cancer diagnosis.
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Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer in adults, with an average life expectancy under treatment of approx. 15 months. GBM is characterised by a complex set of genetic alterations that results in significant disruption of receptor tyrosine kinase (RTK) signaling. We report here an exploration of the pyrazolo[3,4-d]pyrimidine scaffold in search for antiproliferative compounds directed to GBM treatment. Small compound libraries were synthesised and screened against GBM cells to build up structure-antiproliferative activity-relationships (SAARs) and inform further rounds of design, synthesis and screening. 76 novel compounds were generated through this iterative process that found low micromolar potencies against selected GBM lines, including patient-derived stem cells. Phenomics analysis demonstrated preferential activity against glioma cells of the mesenchymal subtype, whereas kinome screening identified colony stimulating factor-1 receptor (CSF-1R) as the lead's target, a RTK implicated in the tumourigenesis and progression of different cancers and the immunoregulation of the GBM microenvironment.
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The central role of dysregulated kinase activity in the etiology of progressive disorders, including cancer, has fostered incremental efforts on drug discovery programs over the past 40 years. As a result, kinase inhibitors are today one of the most important classes of drugs. The FDA approved 73 small molecule kinase inhibitor drugs until September 2021, and additional inhibitors were approved by other regulatory agencies during that time. To complement the published literature on clinical kinase inhibitors, we have prepared a review that recaps this large data set into an accessible format for the medicinal chemistry community. Along with the therapeutic and pharmacological properties of each kinase inhibitor approved across the world until 2020, we provide the synthesis routes originally used during the discovery phase, many of which were only available in patent applications. In the last section, we also provide an update on kinase inhibitor drugs approved in 2021.
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Antineoplásicos/uso terapéutico , Aprobación de Drogas , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Bibliotecas de Moléculas Pequeñas/uso terapéutico , Antineoplásicos/síntesis química , Humanos , Neoplasias/enzimología , Inhibidores de Proteínas Quinasas/síntesis química , Bibliotecas de Moléculas Pequeñas/síntesis química , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Being recognized as the best-tolerated of all metals, the catalytic potential of gold (Au) has thus far been hindered by the ubiquitous presence of thiols in organisms. Herein we report the development of a truly-catalytic Au-polymer composite by assembling ultrasmall Au-nanoparticles at the protein-repelling outer layer of a co-polymer scaffold via electrostatic loading. Illustrating the in vivo-compatibility of the novel catalysts, we show their capacity to uncage the anxiolytic agent fluoxetine at the central nervous system (CNS) of developing zebrafish, influencing their swim pattern. This bioorthogonal strategy has enabled -for the first time- modification of cognitive activity by releasing a neuroactive agent directly in the brain of an animal.
RESUMEN
We describe a versatile, portable, and simple platform that includes a microfluidic electrochemical immunosensor for prostate-specific antigen (PSA) detection. It is based on the covalent immobilization of the anti-PSA monoclonal antibody on magnetic microbeads retained in the central channel of a microfluidic device. Image flow cytometry and scanning electron microscopy were used to characterize the magnetic microbeads. A direct sandwich immunoassay (with horseradish peroxidase-conjugated PSA antibody) served to quantify the cancer biomarker in serum samples. The enzymatic product was detected at -100 mV by amperometry on sputtered thin-film electrodes. Electrochemical reaction produced a current proportional to the PSA level, with a linear range from 10 pg mL-1 to 1500 pg mL-1. The sensitivity was demonstrated by a detection limit of 2 pg mL-1 and the reproducibility by a coefficient of variation of 6.16%. The clinical performance of this platform was tested in serum samples from patients with prostate cancer (PCa), observing high specificity and full correlation with gold standard determinations. In conclusion, this analytical platform is a promising tool for measuring PSA levels in patients with PCa, offering a high sensitivity and reduced variability. The small platform size and low cost of this quantitative methodology support its suitability for the fast and sensitive analysis of PSA and other circulating biomarkers in patients. Further research is warranted to verify these findings and explore its potential application at all healthcare levels.
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Diet in the first years of life is an important factor in growth and development. Dietary protein is a critical macronutrient that provides both essential and nonessential amino acids required for sustaining all body functions and procedures, providing the structural basis to maintain life and healthy development and growth in children. In this study, our aim was to describe the total protein intake, type and food sources of protein, the adequacy to the Population Reference Intake (PRI) for protein by the European Food Safety Authority (EFSA), and the Recommended Dietary Allowance (RDA) by the Institute of Medicine (IoM). Furthermore, we analyzed whether the consumption of dairy products (including regular milk, dairy products, or adapted milk formulas) is associated with nutrient adequacy and the contribution of protein to diet and whole dietary profile in the two cohorts of the EsNuPI (in English, Nutritional Study in the Spanish Pediatric Population) study; one cohort was representative of the Spanish population from one to <10 years old (n = 707) (Spanish reference cohort, SRS) who reported consuming all kinds of milk and one was a cohort of the same age who reported consuming adapted milk over the last year (including follow-on formula, growing up milk, toddler's milk, and enriched and fortified milks) (n = 741) (adapted milk consumers cohort, AMS). The children of both cohorts had a high contribution from protein to total energy intake (16.79% SRS and 15.63% AMS) and a high total protein intake (60.89 g/day SRS and 53.43 g/day AMS). We observed that protein intake in Spanish children aged one to <10 years old was above the European and international recommendations, as well as the recommended percentages for energy intakes. The main protein sources were milk and dairy products (28% SRS and 29% AMS) and meat and meat products (27% SRS and 26% AMS), followed by cereals (16% SRS and 15% AMS), fish and shellfish (8% in both cohorts), eggs (5% SRS and 6% AMS), and legumes (4% in both cohorts). In our study population, protein intake was mainly from an animal origin (meat and meat products, milk and dairy products, fish and shellfish, and eggs) rather than from a plant origin (cereals and legumes). Future studies should investigate the long-term effect of dietary protein in early childhood on growth and body composition, and whether high protein intake affects health later in life.
Asunto(s)
Fenómenos Fisiológicos Nutricionales Infantiles , Dieta/métodos , Proteínas en la Dieta/administración & dosificación , Ingestión de Energía , Familia , Encuestas Nutricionales/métodos , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Encuestas Nutricionales/estadística & datos numéricos , Ingesta Diaria Recomendada , EspañaRESUMEN
Despite the approval of several multikinase inhibitors that target SRC and the overwhelming evidence of the role of SRC in the progression and resistance mechanisms of many solid malignancies, inhibition of its kinase activity has thus far failed to improve patient outcomes. Here we report the small molecule eCF506 locks SRC in its native inactive conformation, thereby inhibiting both enzymatic and scaffolding functions that prevent phosphorylation and complex formation with its partner FAK. This mechanism of action resulted in highly potent and selective pathway inhibition in culture and in vivo. Treatment with eCF506 resulted in increased antitumor efficacy and tolerability in syngeneic murine cancer models, demonstrating significant therapeutic advantages over existing SRC/ABL inhibitors. Therefore, this mode of inhibiting SRC could lead to improved treatment of SRC-associated disorders. SIGNIFICANCE: Small molecule-mediated inhibition of SRC impairing both catalytic and scaffolding functions confers increased anticancer properties and tolerability compared with other SRC/ABL inhibitors.
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Neoplasias Óseas/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Quinasa 1 de Adhesión Focal/antagonistas & inhibidores , Piperidinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-abl/antagonistas & inhibidores , Pirazoles/farmacología , Pirimidinas/farmacología , Bibliotecas de Moléculas Pequeñas/farmacología , Familia-src Quinasas/antagonistas & inhibidores , Animales , Apoptosis , Neoplasias Óseas/metabolismo , Neoplasias Óseas/secundario , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Conformación Proteica , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Familia-src Quinasas/química , Familia-src Quinasas/metabolismoRESUMEN
Port-wine stains (PWS) represent a group of vascular malformations that are usually accompanied by psychological distress for affected patients, often reflected in high treatment demand. Although the pulsed-dye laser (PDL) was established as standard therapy for PWS more than a decade ago, therapeutic outcome may be unsatisfactory. One of the main drawbacks to successful PDL therapy is PWS revascularization shortly after laser exposure. Therefore, inhibition of revascularization should improve therapeutic outcome of PDL therapy. In this study, we first evaluated the effects of various light energies on normal cutaneous vessels over a period of 14 days, particularly the proliferation and stem cell marker expression of dermal endothelial cells, which were found to be highest 8 days following laser exposure. We found that PDL exposure induced dose-dependent damage of dermal vessels up to energy densities of 6 J/cm(2), above which no increase in PDL-induced effects were observed with the energies employed in this study. In dermal endothelial cells of PDL-exposed skin, we found strong expression of the proliferation marker Ki-67 as well as the stem cell marker nestin but not other stem cell markers such as CD133 and CD166. The influence of rapamycin (RPM), used as an adjuvant to PDL exposure, was also investigated. RPM administration reduced Ki-67 and nestin expression in dermal endothelial cells and increased PDL-induced destruction of dermal vessels, indicating that the use of RPM after PDL exposure may be an interesting new approach for prolonging and improving PWS laser therapeutic outcome.
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Antibióticos Antineoplásicos/administración & dosificación , Terapia por Láser/métodos , Mancha Vino de Oporto/radioterapia , Sirolimus/administración & dosificación , Piel , Células Madre , Antígeno AC133 , Administración Tópica , Antígenos CD/metabolismo , Biopsia , Moléculas de Adhesión Celular Neuronal/metabolismo , División Celular/efectos de la radiación , Terapia Combinada , Relación Dosis-Respuesta en la Radiación , Células Endoteliales/citología , Células Endoteliales/metabolismo , Células Endoteliales/efectos de la radiación , Proteínas Fetales/metabolismo , Glicoproteínas/metabolismo , Humanos , Proteínas de Filamentos Intermediarios/metabolismo , Antígeno Ki-67/metabolismo , Terapia por Láser/efectos adversos , Láseres de Colorantes/efectos adversos , Proteínas del Tejido Nervioso/metabolismo , Nestina , Péptidos/metabolismo , Mancha Vino de Oporto/metabolismo , Mancha Vino de Oporto/patología , Recurrencia , Piel/irrigación sanguínea , Piel/citología , Piel/efectos de la radiación , Células Madre/citología , Células Madre/metabolismo , Células Madre/efectos de la radiación , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/efectos de la radiaciónRESUMEN
The promising potential of bioorthogonal catalysis in biomedicine is inspiring incremental efforts to design strategies that regulate drug activity in living systems. To achieve this, it is not only essential to develop customized inactive prodrugs and biocompatible metal catalysts but also the right physical environment for them to interact and enable drug production under spatial and/or temporal control. Toward this goal, here, we report the first inactive precursor of the potent broad-spectrum anticancer drug paclitaxel (a.k.a. Taxol) that is stable in cell culture and labile to Pd catalysts. This new prodrug is effectively uncaged in cancer cell culture by Pd nanosheets captured within agarose and alginate hydrogels, providing a biodegradable catalytic framework to achieve controlled release of one of the most important chemotherapy drugs in medical practice. The compatibility of bioorthogonal catalysis and physical hydrogels opens up new opportunities to administer and modulate the mobility of transition metal catalysts in living environs.
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Antineoplásicos/química , Antineoplásicos/farmacología , Hidrogeles/química , Nanoestructuras/química , Paclitaxel/química , Paclitaxel/farmacología , Paladio/química , Antineoplásicos/metabolismo , Catálisis , Línea Celular Tumoral , Humanos , Modelos Moleculares , Conformación Molecular , Paclitaxel/metabolismo , Profármacos/metabolismoRESUMEN
Diet quality is a modifiable factor that may contribute to the onset of diet-related chronic diseases. Currently, in Spain there are no studies that examine the intakes and sources for total carbohydrates, starch, total sugar, and fiber by both children consuming all kind of milks and children regularly consuming adapted milk formulas. Our goal was to evaluate the contribution of different food groups to total carbohydrates, starch, total sugar, and fiber consumption within the EsNuPI study participants by assessing their usual intakes by applying two 24 h dietary recalls that were completed by 1448 children (1 to <10 years) divided into two cohorts: one Spanish Reference Cohort (SRS) of the general population (n = 707) and another cohort which included children consuming adapted milks including follow-on milk, toddler's or growing up milk, fortified and enriched milks, here called Adapted Milk Consumers Cohort" (AMS) (n = 741). Estimation of the usual intake showed that nutrient intake increased with age for all nutrients except for fiber. The percentage of children by age and gender who met the reference intake (RI) range for total carbohydrates, was in all groups more than 50% of individuals, except for girls aged 6 to <10 years from the reference cohort in which only 46.9% complied the RI. Median fiber intake, both in the SRS and the AMS, was well below the adequate intake (AI) for children between 3 and 10 years. Main total carbohydrates sources were cereals, followed by milk and dairy products, fruits, bakery and pastry, vegetables and sugars and sweets. The highest contributors to starch intakes were cereals, bakery and pastry, vegetables, and fruits. Major sources of total sugar intakes were milk and dairy products, fruits, bakery and pastry, sugars and sweets, vegetables, and cereals. Nonetheless, milk and dairy products, and fruits, mainly provided lactose and fructose, respectively, which are not considered free sugars. Higher contribution to fiber intakes was provided by fruits, cereals, vegetables and bakery and pastry. There were no significant differences in relation with the total sugar intake according to the body mass index (BMI) between SRS and AMS. The present study suggests a high proportion of children had total carbohydrates intakes in line with recommendations by public health authorities, but still a significant number presented insufficient total carbohydrate and fiber intakes, while total sugar consumption was high, with no major differences between SRS and AMS cohorts.
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Fenómenos Fisiológicos Nutricionales Infantiles/fisiología , Carbohidratos de la Dieta/administración & dosificación , Fibras de la Dieta/administración & dosificación , Azúcares de la Dieta/administración & dosificación , Ingestión de Alimentos/fisiología , Conducta Alimentaria/fisiología , Abastecimiento de Alimentos , Evaluación Nutricional , Almidón , Animales , Niño , Preescolar , Enfermedad Crónica/prevención & control , Estudios de Cohortes , Femenino , Humanos , Lactante , Fórmulas Infantiles , Masculino , Leche , Ingesta Diaria Recomendada , EspañaRESUMEN
The present study aimed to assess energy intake, nutrient profile and food sources in Spanish children participating in the EsNuPI ("Estudio Nutricional en Población Infantil Española") study. Plausibility of energy intake and adequacy of nutrient intakes to international recommendations were analyzed in a final sample of 1448 subjects (728 boys and 720 girls) and one group representative of the 1 to <10 years old urban Spanish children (reference sample (n = 707)) who consumed milk and one of the same age who consumed adapted milk over the last year (adapted milk consumers sample (n = 741)) were compared. Both groups completed data of a face-to-face and a telephone 24-h dietary recalls. Both the reference and the adapted milk consumers samples reported an adequate daily energy intake (1503 kcal/day and 1404 kcal/day); and a high contribution to total energy from protein (16.5% and 15.6%) and fat (36.5% and 35.9%). Also, a high percentage of children from both samples were below the lower limit of the recommendations for carbohydrates (47.8% and 39.3%). As the percentage of plausible energy reporters was high for both groups (84.7% and 83.5%, respectively), data for the whole sample were analyzed. Milk and dairy, cereals, meat and derived products, fats and oils, bakery and pastry, fruits and vegetables contributed to about 80% of the total energy intake in both groups. However, the reference sample reported significantly more contribution to energy from cereals, meat and meat products, bakery and pastry and ready to cook/eat foods; meanwhile, the adapted milk consumers sample reported significantly more energy from milk and dairy products, fruits and eggs. Those results suggest that adapted milk consumers have better adherence to the food-based dietary guidelines. Further analyses are warranted to characterize food patterns and the quality of the diet in the EsNuPI study population.
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Dieta , Ingestión de Energía , Nutrientes , Niño , Preescolar , Estudios Transversales , Conducta Alimentaria , Femenino , Humanos , Lactante , Masculino , Política Nutricional , Encuestas Nutricionales , España/epidemiologíaRESUMEN
We aimed to determine the usual intake of total fat, fatty acids (FAs), and their main food sources in a representative cohort of the Spanish pediatric population aged 1 to <10 years (n = 707) who consumed all types of milk and an age-matched cohort who consumed adapted milk over the last year (including follow-on formula, toddler's milk, growing-up milk, and fortified and enriched milks) (n = 741) who were participants in the EsNuPI study (in English, Nutritional Study in the Spanish Pediatric Population). Dietary intake, measured through two 24 h dietary recalls, was compared to the European Food Safety Authority (EFSA) and the Food and Agriculture Organization of the United Nations (UN-FAO) recommendations. Both cohorts showed a high intake of saturated fatty acids (SFAs), according to FAO recommendations, as there are no numerical recommendations for SFAs at EFSA. Also, low intake of essential fatty acids (EFAs; linoleic acid (LA) and α-linolenic acid (ALA)) and long-chain polyunsaturated fatty acids (LC-PUFA) of the n-3 series, mainly docosahexaenoic acid (DHA) were observed according to EFSA and FAO recommendations. The three main sources of total fat and different FAs were milk and dairy products, oils and fats, and meat and meat products. The consumption of adapted milk was one of the main factors associated with better adherence to the nutritional recommendations of total fat, SFAs, EFAs, PUFAs; and resulted as the main factor associated with better adherence to n-3 fatty acids intake recommendations. Knowledge of the dietary intake and food sources of total fat and FAs in children could help in designing and promoting effective and practical age-targeted guidelines to promote the consumption of EFA- and n-3 PUFA-rich foods in this stage of life.
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Fenómenos Fisiológicos Nutricionales Infantiles/fisiología , Grasas de la Dieta/administración & dosificación , Ingestión de Alimentos/fisiología , Familia , Ácidos Grasos Esenciales/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Conducta Alimentaria/fisiología , Alimentos Fortificados , Fórmulas Infantiles , Leche , Encuestas Nutricionales , Necesidades Nutricionales , Ingesta Diaria Recomendada , Factores de Edad , Animales , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , EspañaRESUMEN
Dietary patterns (DPs) are known to be tied to lifestyle behaviors. Understanding DPs and their relationships with lifestyle factors can help to prevent children from engaging in unhealthy dietary practices. We aimed to describe DPs in Spanish children aged 1 to <10 years and to examine their associations with sociodemographic and lifestyle variables. The consumption of toddler and young children milk formulas, enriched and fortified milk within the Spanish pediatric population is increasing, and there is a lack of evidence whether the consumption of this type of milk is causing an impact on nutrient intakes and if they are helping to reach the nutrient recommendations. Within the Nutritional Study in the Spanish Pediatric Population (EsNuPI), we considered two study cohorts and three different age groups in three year-intervals in each of them. The study cohort included 740 children in a representative sample of the urban non-vegan Spanish population and 772 children in a convenience cohort of adapted milk consumers (AMS) (including follow-on formula, toddler's milk, growing up milk, and fortified and enriched milks) who provided information about sociodemographics, lifestyle, and dietary habits; a food frequency questionnaire was used for the latter. Principal component analysis was performed to identify DPs from 18 food groups. Food groups and sociodemographic/lifestyle variables were combined through a hierarchical cluster algorithm. Three DPs predominated in every age group and study sample: a palatable energy-dense food dietary pattern, and two Mediterranean-like DPs. However, children from the AMS showed a predominant dietary pattern markedly related to the Mediterranean diet, with high consumption of cereals, fruits and vegetables, as well as milk and dairy products. The age of children and certain lifestyle factors, namely level of physical activity, parental education, and household income, correlated closely with the dietary clusters. Thus, the findings provide insight into designing lifestyle interventions that could reverse the appearance of unhealthy DPs in the Spanish child population.