RESUMEN
BACKGROUND: Parkinson's disease (PD), the most prevalent type of Parkinsonism, is a progressive neurological condition characterized by a range of motor and non-motor symptoms. The complicated etiology of PD is thought to involve a summation of aging, genetic predisposition, and environmental variables. However, the α-synuclein protein plays a significant role in the disease's pathophysiology. MATERIALS AND METHODS: The UAS-α-Syn and Ddc-Gal4 strains were crossed to produce offspring referred to as PD flies. The entire population of flies was divided into five groups, each having about 100 flies and five replicates. The control group (w1118) and the PD group not receiving treatment were exposed to lauric acid (LA)/levodopa (LD)-free diet, while the PD groups that received treatments were fed with either a 250 mg/kg LA diet, a 250 mg/kg LD diet, or a combination of the two for 21 days. Longevity, geotaxis, and olfactory assays were performed in addition to other biochemical tests. RESULTS: As a result of the overexpression of α-synuclein, the locomotive capacity, lifespan, and antioxidant status were all significantly (p < .05) reduced, and the apoptotic and neuroinflammatory activities were increased. Nevertheless, the majority of the treated flies improved significantly (p < .05). CONCLUSION: LA, whether combined with LD or not, elicited a significant response in α-synuclein/dopa decarboxylase genetically modified Drosophila melanogaster Parkinsonism models.
Asunto(s)
Apoptosis , Modelos Animales de Enfermedad , Drosophila melanogaster , Ácidos Láuricos , Levodopa , Trastornos Parkinsonianos , Animales , Drosophila melanogaster/efectos de los fármacos , Ácidos Láuricos/farmacología , Ácidos Láuricos/administración & dosificación , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/metabolismo , Levodopa/farmacología , Levodopa/administración & dosificación , Apoptosis/efectos de los fármacos , alfa-Sinucleína/metabolismo , Animales Modificados Genéticamente , Estrés Oxidativo/efectos de los fármacos , Longevidad/efectos de los fármacos , MasculinoRESUMEN
Trazodone is a triazolpyridine derivative approved for the treatment of depression, and currently marketed as oral formulations. The transdermal administration of this drug could reduce side effects, related to peak plasma concentration, and improve patient adherence due to a reduced administration frequency. The aims of this work were: (a) the evaluation of the effect of pH vehicle and permeation enhancers on trazodone permeability across porcine skin ex-vivo; (b) the development and optimization of a transdermal drug delivery system containing trazodone hydrochloride. From the results obtained, it was found that the effect of pH of the vehicle on the permeation of trazodone across the skin is quite complex, because it influences both solubility and partitioning and that the presence of fatty acids in the vehicle has a notable effect on permeation (the enhancement factor obtained was approx. 100). For both the fatty acid selected (oleic and lauric) a parabolic relationship between the transdermal flux and the concentration was found, with an optimum activity in the range 2-3 %. In the second part of the work, different patches were prepared and tested ex-vivo. Overall, the results obtained seem to highlight that drug loading, rather than the components of the adhesive matrix, plays the most relevant role for the permeation of trazodone. The addition of lauric acid, which produced a considerable enhancement in solution, was not effective when included in the patch. The obtained data are promising although probably not clinically relevant for the treatment of depression, but might be interesting for the treatment of insomnia and anxiety disorder, which require much lower doses.
Asunto(s)
Administración Cutánea , Absorción Cutánea , Trazodona , Trazodona/administración & dosificación , Trazodona/farmacocinética , Animales , Porcinos , Absorción Cutánea/efectos de los fármacos , Piel/metabolismo , Piel/efectos de los fármacos , Permeabilidad , Ácido Oléico/química , Solubilidad , Concentración de Iones de Hidrógeno , Ácidos Láuricos/química , Ácidos Láuricos/administración & dosificación , Parche Transdérmico , Química Farmacéutica/métodos , Antidepresivos de Segunda Generación/administración & dosificación , Antidepresivos de Segunda Generación/farmacocinética , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Myocardial damage significantly impacts the prognosis of patients with cancer; however, the mechanisms of myocardial damage induced by cancer and its treatment remain unknown. We previously reported that medium-chain fatty acids (MCFAs) improve cancer-induced myocardial damage but did not evaluate the differences in effect according to MCFA type. Therefore, this study investigated the role of inflammatory cytokines in cancer-induced myocardial damage and the effects of three types of MCFAs (caprylic acid [C8], capric acid [C10], and lauric acid [C12]). In a mouse model, the C8 diet showed a greater effect on improving myocardial damage compared with C10 and C12 diets. Myocardial tubes differentiated from H9C2 cardiomyoblasts demonstrated increased mitochondrial oxidative stress, decreased membrane potential and mitochondrial volume, and inhibited myocardial tube differentiation following treatment with high-mobility group box-1 (HMGB1) but not interleukin-6 and tumor necrosis factor-α cytokines. However, HMGB1 treatment combined with C8 improved HMGB1-induced mitochondrial damage, enhanced autophagy, and increased mitochondrial biogenesis and maturation. However, these effects were only partial when combined with beta-hydroxybutyrate, a C8 metabolite. Thus, HMGB1 may play an important role in cancer-related myocardial damage. C8 counteracts HMGB1's effects and improves cancer-related myocardial damage. Further clinical studies are required to investigate the effects of C8.
Asunto(s)
Caprilatos , Proteína HMGB1 , Animales , Proteína HMGB1/metabolismo , Ratones , Caprilatos/farmacología , Estrés Oxidativo/efectos de los fármacos , Miocardio/metabolismo , Miocardio/patología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Masculino , Ácidos Láuricos/farmacología , Línea Celular , Citocinas/metabolismo , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Ácidos Decanoicos/farmacología , Ácido 3-Hidroxibutírico/farmacología , Autofagia/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
To satisfy the demands of the food industry, innovative flavor enhancers need to be developed urgently to increase the food flavor. In our work, N-lauroyl phenylalanine (LP) was prepared from phenylalanine (l-Phe) and lauric acid (Lau) in water through the use of commercial enzymes (Promatex, Sumizyme FP-G, and Trypsin), and its flavor-presenting properties and mechanism were investigated. The highest LP yields obtained under one-factor optimized conditions were 61.28, 63.43, and 77.58%, respectively. Sensory assessment and an e-tongue test revealed that 1 mg/L LP enhanced the kokumi, saltiness, and umami of the simulated chicken broth solution and attenuated the bitterness of the l-isoleucine solution. The molecular simulation results suggested that the mechanisms of LP enhancement of kokumi and umami were related to hCaSR and hT1R1-hT1R3, and that hydrophobic forces and hydrogen bonds were involved in the binding of LP to taste receptors. The results implied that LP is a potential flavor enhancer for food applications.
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Aromatizantes , Fenilalanina , Gusto , Fenilalanina/química , Aromatizantes/química , Aromatizantes/metabolismo , Humanos , Ácidos Láuricos/química , Masculino , Animales , Biocatálisis , Adulto , Pollos , Femenino , Adulto JovenRESUMEN
The aim of this study was the evaluation of suitability of novel mucoadhesive hydrogel platforms for the delivery of therapeutics useful for the management of disorders related to the gastrointestinal tract (GI). At this purpose, here we describe the preparation, the physicochemical characterization and drug delivery behaviour of novel hydrogels, based on self-assembling lipopeptides (MPD02-09), obtained by covalently conjugating lauric acid (LA) to SNA's peptide derivatives gotten by variously combining D- and L- amino acid residues. LA conjugation was aimed at improving the stability of the precursor peptides, obtaining amphiphilic structures, and triggering the hydrogels formation through the self-assembling. Budesonide (BUD), an anti-inflammatory drug, was selected as model because of its use in the treatment in GI disorders. Preliminary studies were performed to correlate the chemical structure of the conjugates with the key physicochemical properties of the materials for drug delivery. Two lipopeptides, MPD03 and MPD08, were found to form hydrogels (MPD03h and MPD08h, respectively) with characteristics suitable for drug delivery. These materials showed mucoadhesiveness of about 60 %. In vitro studies carried out with BUD loaded hydrogels showed about 70 % drug release within 6 h. Wound healing assessed in Caco-2 and HaCaT cells, showed reduction of cell-free area to values lower than 10 %. Taking together these results MPD03h and MPD08h have been shown to be excellent candidates for BUD delivery.
Asunto(s)
Budesonida , Preparaciones de Acción Retardada , Liberación de Fármacos , Hidrogeles , Hidrogeles/química , Humanos , Células CACO-2 , Budesonida/química , Budesonida/administración & dosificación , Cicatrización de Heridas/efectos de los fármacos , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Lipopéptidos/química , Lipopéptidos/administración & dosificación , Ácidos Láuricos/química , Sistemas de Liberación de Medicamentos/métodos , Células HaCaT , Péptidos/química , Péptidos/administración & dosificaciónRESUMEN
The hydrolysis of polysorbate surfactants in large molecule drug product formulations caused by residual host cell proteins presents numerous stability concerns for pharmaceuticals. The fatty acids (FA) released by polysorbate hydrolysis can nucleate into particulates or challenge the conformational stability of the proteinaceous active pharmaceutical ingredient (API). The loss of intact polysorbate may also leave the Drug Product (DP) vulnerable to interfacial stresses. Polysorbate 20 and 80 are available in several different quality grades (Multi-compendial, Super Refined, Pure Lauric Acid (PLA)/Pure Oleic Acid (POA)). All variations of polysorbate as well as three alternative surfactants: Brij L23, Brij O20 and Poloxamer 188 were compared for their ability to protect against air-water interfacial stresses as well as their risk for developing particulates when in the presence of lipoprotein lipase (LPL) (Pseudomonas). Results show a meaningful difference in the timing and morphology of FA particle formation depending on the type of polysorbate used. All grades of polysorbate, while susceptible to hydrolysis, still offered sufficient protection to interfacial stresses, even when hydrolyzed to concentrations as low as 0.005 % (w/v). Alternative surfactants that lack an ester bond were resistant to lipase degradation and showed good protection against shaking stress.
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Ácidos Grasos , Polisorbatos , Tensoactivos , Polisorbatos/química , Tensoactivos/química , Ácidos Grasos/química , Ácidos Grasos/metabolismo , Hidrólisis , Esterasas/metabolismo , Estabilidad de Medicamentos , Tamaño de la Partícula , Ácidos Láuricos/químicaRESUMEN
Starch, lipids, and proteins are key macronutrients in starchy foods. Their interactions during processing can form starch-lipid-protein ternary complexes, significantly affecting food quality. Ultrasonic treatment, as a common processing method, is expected to regulate the quality of starchy foods by influencing the formation of ternary complexes. This study aimed to understand the effect of ultrasonic pretreatment on the formation of starch-lipid-protein ternary complexes using various types of starches. Wheat starch (WS), maize starch (MS), and potato starch (PS) were gelatinized and treated with ultrasound at various power densities (0-40 W/L) to form complexes with lauric acid (LA) and ß-lactoglobulin (ßLG), respectively. Ultrasound increased the amylose content of gelatinized WS, MS, and PS and shifted their chain length distribution towards the short chains. Results from Fourier transform infrared spectroscopy, laser confocal micro-Raman, X-ray diffraction, and differential scanning calorimetry showed that the largest amount of WS-LA-ßLG complexes was formed at the ultrasonic power density of 10 W/L, and MS-LA-ßLG and PS-LA-ßLG complexes at 20 W/L. Additionally, ultrasound enhanced the content of resistant starch (RS) in the starch-LA-ßLG complexes. The RS content increased from 14.12 % to 18.31 % for WS-LA-ßLG, and from 19.18 % and 20.69 % to 27.60 % and 28.63 % for MS-LA-ßLG and PS-LA-ßLG complexes, respectively. This study presents an approach for facilitating the formation of ternary complexes, contributing to the development of low-GI functional foods.
Asunto(s)
Lactoglobulinas , Ácidos Láuricos , Almidón , Ácidos Láuricos/química , Almidón/química , Lactoglobulinas/química , Ondas Ultrasónicas , DigestiónRESUMEN
This study aimed to explore the effects of various lipids on the structure, cooking quality, and in vitro starch digestibility of extruded buckwheat noodles (EBNs) with and without 20% high-amylose corn starch (HACS). Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction revealed that lauric acid bound more strongly to starch than did stearic acid and oleic acid, and the binding capacity of fatty acids with starch was stronger than that of glycerides. The presence of HACS during extrusion facilitated increased formation of starch-lipid complexes. Evaluations of cooking quality and digestion characteristics showed that EBNs containing 20% HACS and 0.5% glycerol monooleate demonstrated the lowest cooking loss (7.28%), and that with 20% HACS and 0.5% oleic acid displayed the lowest predicted glycemic index (pGI) (63.54) and highest resistant starch (RS) content (51.64%). However, excessive starch-lipid complexes were detrimental to EBNs cooking quality and the resistance of starch to digestive enzymes because of the damage to the continuity of the starch gel network. This study establishes a fundamental basis for the development of EBNs with superior cooking quality and a relatively lower GI.
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Culinaria , Digestión , Fagopyrum , Ácidos Grasos , Almidón , Fagopyrum/química , Ácidos Grasos/química , Almidón/química , Glicéridos/química , Índice Glucémico , Espectroscopía Infrarroja por Transformada de Fourier , Amilosa/química , Difracción de Rayos X , Rastreo Diferencial de Calorimetría , Ácidos Esteáricos/química , Ácido Oléico/química , Ácidos Láuricos/químicaRESUMEN
Previous RS5 (type 5 resistant starch) research has significantly broadened starch use and benefited society, yet the effects of the molecular weight of amylose on RS5 remain underexplored. In this study, amyloses with different molecular weights were complexed with caproic acid (C6), lauric acid (C12), and stearic acid (C18) to observe the effects of the molecular weight of amylose on the structure and in vitro digestive properties of RS5. Gel permeation chromatography revealed that the peak average molecular weight (Mp) values of high-amylose cornstarch NF-CGK (CGK), high-amylose cornstarch obtained via cornstarch via autoclave (high temperature and high pressure)-cooling combined pullulanase enzymatic hydrolysis (CTE), and high-amylose cornstarch NF-G370 (HCK) were 21,282, 171,537, and 188,084 before fatty acid complexation, respectively. Additionally, their weight average molecular weight (Mw) values of 32,429, 327,344, and 410,610 and hydrolysis rates of 58.12 %, 86.77 %, and 64.58 %, respectively. The hydrolysis rate of low-Mw amylose (GCK) complexes with fatty acids was lower than that of HCK and CTE starch-lipid complexes. However, HCK and CTE having similar molecular weights, there was no significant difference in the hydrolysis rate of starch-lipid complexes. X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy and complexing index analyses confirmed the formation of these complexes. This study proposed the mechanism of RS5 formation and provided guidance for its future development.
Asunto(s)
Amilosa , Ácidos Láuricos , Peso Molecular , Amilosa/química , Ácidos Láuricos/química , Hidrólisis , Almidón/química , Almidón/metabolismo , Digestión , Ácidos Esteáricos/química , Lípidos/química , CaprilatosRESUMEN
The effects of complexing conditions on the formation of amylose-lipid-protein complexes and relationships between structure and digestion of amylose-lipid and amylose-lipid-protein complexes were poorly understood. The objective of this study was to investigate the effects of complexing time (0, 0.5, 2, 4 and 6 h) and temperature (60, 70, 80, 90 and 100 °C) on the structure and in vitro amylolysis of amylose-lauric acid (AM-LA) and amylose-lauric acid-ß-lactoglobulin (AM-LA-ßLG) complexes, and to understand the relationships between structure and in vitro digestiblity of these complexes. Longer complexing time and higher complexing temperature promoted the formation of greater amounts of the more stable type II crystallites than type I crystallites in both AM-LA and AM-LA-ßLG complexes, which in turn decreased the rate and extent of the complexes digestion to a greater extent. Correlation analyses between parameters for structure and digestion kinetics showed that both the quantity of AM-LA and AM-LA-ßLG complexes and the quality of their arrangement into V-type crystallites influenced their rate and extent of digestion. This study demonstrates that AM-LA and AM-LA-ßLG complexes can be prepared with designed structural and functional properties tailored for various applications.
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Amilosa , Lactoglobulinas , Amilosa/química , Lactoglobulinas/química , Lactoglobulinas/metabolismo , Ácidos Láuricos/química , Temperatura , Cinética , Digestión , HidrólisisRESUMEN
There is increasing pharmaceutical interest in deep eutectic solvents not only as a green alternative to organic solvents in drug manufacturing, but also as liquid formulation for drug delivery. The present work introduces a hydrophobic deep eutectic solvent (HDES) to the field of lipid-based formulations (LBF). Phase behavior of a mixture with 2:1 M ratio of decanoic- to dodecanoic acid was studied experimentally and described by thermodynamic modelling. Venetoclax was selected as a hydrophobic model drug and studied by atomistic molecular dynamics simulations of the mixtures. As a result, valuable molecular insights were gained into the interaction networks between the different components. Moreover, experimentally the HDES showed greatly enhanced drug solubilization compared to conventional glyceride-based vehicles, but aqueous dispersion behavior was limited. Hence surfactants were studied for their ability to improve aqueous dispersion and addition of Tween 80 resulted in lowest droplet sizes and high in vitro drug release. In conclusion, the combination of HDES with surfactant(s) provides a novel LBF with high pharmaceutical potential. However, the components must be finely balanced to keep the integrity of the solubilizing HDES, while enabling sufficient dispersion and drug release.
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Composición de Medicamentos , Liberación de Fármacos , Interacciones Hidrofóbicas e Hidrofílicas , Lípidos , Simulación de Dinámica Molecular , Solubilidad , Solventes , Tensoactivos , Solventes/química , Tensoactivos/química , Lípidos/química , Composición de Medicamentos/métodos , Polisorbatos/química , Ácidos Láuricos/química , Química Farmacéutica/métodos , Sulfonamidas/química , Sulfonamidas/administración & dosificación , Aceites/químicaRESUMEN
Lauric acid (LA), a saturated fatty acid with 12 carbon atoms, is widely regarded as a healthy fatty acid that plays an important role in disease resistance and improving immune physiological function. The objective of this study was to determine the effects of dietary lauric acid on the growth performance, antioxidant capacity, non-specific immunity and intestinal microbiology, and evaluate the potential of lauric acids an environmentally friendly additive in swimming crab (Portunus trituberculatus) culture. A total of 192 swimming crabs with an initial body weight of 11.68 ± 0.02 g were fed six different dietary lauric acid levels, the analytical values of lauric acid were 0.09, 0.44, 0.80, 1.00, 1.53, 2.91 mg/g, respectively. There were four replicates per treatment and 8 juvenile swimming crabs per replicate. The results indicated that final weight, percent weight gain, specific growth rate, survival and feed intake were not significantly affected by dietary lauric acid levels; however, crabs fed diets with 0.80 and 1.00 mg/g lauric acid showed the lowest feed efficiency among all treatments. Proximate composition in hepatopancreas and muscle were not significantly affected by dietary lauric acid levels. The highest activities of amylase and lipase in hepatopancreas and intestine were found at crabs fed diet with 0.80 mg/g lauric acid (P < 0.05), the activity of carnitine palmityl transferase (CPT) in hepatopancreas and intestine significantly decreased with dietary lauric acid levels increasing from 0.09 to 2.91 mg/g (P < 0.05). The lowest concentration of glucose and total protein and the activity of alkaline phosphatase in hemolymph were observed at crabs fed diets with 0.80 and 1.00 mg/g lauric acid among all treatments. The activity of GSH-Px in hepatopancreas significantly increased with dietary lauric acid increasing from 0.09 to 1.53 mg/g, MDA in hepatopancreas and hemolymph was not significantly influenced by dietary lauric acid levels. The highest expression of cat and gpx in hepatopancreas were exhibited in crabs fed diet with 1.00 mg/g lauric acid, however, the expression of genes related to the inflammatory signaling pathway (relish, myd88, traf6, nf-κB) were up-regulated in the hepatopancreas with dietary lauric acid levels increasing from 0.09 to 1.00 mg/g, moreover, the expression of genes related to intestinal inflammatory, immune and antioxidant were significantly affected by dietary lauric acid levels (P < 0.05). Crabs fed diet without lauric acid supplementation exhibited higher lipid drop area in hepatopancreas than those fed the other diets (P < 0.05). The expression of genes related to lipid catabolism was up-regulated, however, and the expression of genes related to lipid synthesis was down-regulated in the hepatopancreas of crabs fed with 0.80 mg/g lauric acid. Lauric acid improved hepatic tubular integrity, and enhanced intestinal barrier function by increasing peritrophic membrane (PM) thickness and upregulating the expression of structural factors (per44, zo-1) and intestinal immunity-related genes. In addition, dietary 1.00 mg/g lauric acid significantly improved the microbiota composition of the intestinal, increased the abundance of Actinobacteria and Rhodobacteraceae, and decreased the abundance of Vibrio, thus maintaining the microbiota balance of the intestine. The correlation analysis showed that there was a relationship between intestinal microbiota and immune-antioxidant function. In conclusion, the dietary 1.00 mg/g lauric acid is beneficial to improve the antioxidant capacity and intestinal health of swimming crab.
Asunto(s)
Alimentación Animal , Antioxidantes , Braquiuros , Dieta , Suplementos Dietéticos , Microbioma Gastrointestinal , Ácidos Láuricos , Animales , Braquiuros/inmunología , Braquiuros/efectos de los fármacos , Braquiuros/crecimiento & desarrollo , Braquiuros/microbiología , Ácidos Láuricos/farmacología , Ácidos Láuricos/administración & dosificación , Alimentación Animal/análisis , Antioxidantes/metabolismo , Dieta/veterinaria , Suplementos Dietéticos/análisis , Microbioma Gastrointestinal/efectos de los fármacos , Inmunidad Innata/efectos de los fármacos , Intestinos/efectos de los fármacos , Intestinos/inmunología , Distribución Aleatoria , Relación Dosis-Respuesta a DrogaRESUMEN
The present study was carried out to investigate the proximate composition, fatty acid (FA) profile and volatile compounds (VC) of cooked green licuri (Syagrus coronata) - an unripe stage that is then cooked - and naturally ripe licuri almonds. The FA profiles were determined by gas chromatography (GC) and the VC composition was evaluated using headspace-solid-phase microextraction coupled with GC-MS. The cooked green licuri presented higher moisture, and lower contents of ashes, proteins and lipids than naturally ripe licuri almonds. The FA profiles of cooked green licuri and naturally ripe licuri almonds showed that saturated FAs were predominant (80%) in both samples, and the concentrations of lauric, palmitic, and oleic acids in naturally ripe licuri almonds were higher than those in cooked green licuri. Limonene was the predominant compound in naturally ripe licuri almonds. The main class of VC in the cooked green licuri were aldehydes, with 3-methyl-butanal and furfural being the main species. Alcohols, such as 3-methyl-butanol and 2-heptanol, were the main class of VC in naturally ripe licuri almonds. Among the volatile compounds, 1-hexanol and 2-nonanone contributed to the aroma of cooked green licuri almonds, whereas 2-heptanone, ethanol, and limonene contributed to the aroma of naturally ripe licuri almonds (almonds not subjected to any cooking process). In a word, cooked green licuri and naturally riped licuri almonds, despite having different proximate compositions, present similar fatty acid profile and distinct aromatic characteristics. Therefore, cooked green licuri and naturally riped licuri almonds are an alternative source of nutrient and could be investigated for the use in the food industry to enhance flavor and aroma to new products.
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Culinaria , Ácidos Grasos , Cromatografía de Gases y Espectrometría de Masas , Compuestos Orgánicos Volátiles , Compuestos Orgánicos Volátiles/análisis , Ácidos Grasos/análisis , Brasil , Microextracción en Fase Sólida , Ciclohexenos/análisis , Terpenos/análisis , Limoneno/análisis , Odorantes/análisis , Ácido Palmítico/análisis , Ácido Oléico/análisis , Aldehídos/análisis , Ácidos Láuricos/análisis , Pentanoles/análisisRESUMEN
Although inflammation is primarily a protective response guarding the human body, it can result in a variety of chronic diseases such as allergies, auto-immune, cardiovascular diseases, and cancer. In NF-κB-mediated inflammation, many small molecules and food compounds characterized as nutraceuticals have shown positive effects associated with immunomodulatory properties. We investigated the effects of selected bioactive small molecules, commonly found in food components, vanillyl alcohol (VA) and lauric acid (LA), on different cell lines exposed to pro-inflammatory stimuli, lipopolysaccharide (LPS), and the food allergen actinidin (Act d 1). Pro-inflammatory cytokines were downregulated in response to both VA and LA, and this downregulation was caused by a decrease in the activation of the NF-κB pathway and the translocation of p65, the pathway's major component. Small nutraceutical molecules, VA and LA, showed not only inhibition of the pro-inflammatory cytokines, but also inhibition of the NF-κB activation, and reduced translocation of the p65 component. The present study may contribute to the therapeutic use of these molecules for various inflammatory diseases, which have in common an increased expression of pro-inflammatory cytokines and NF-κB-mediated inflammation.
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Citocinas , Inflamación , Lipopolisacáridos , FN-kappa B , Transducción de Señal , Citocinas/metabolismo , Humanos , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Regulación hacia Abajo/efectos de los fármacos , Ácidos Láuricos/farmacología , Alérgenos/inmunología , Animales , Hipersensibilidad a los Alimentos/metabolismo , Hipersensibilidad a los Alimentos/tratamiento farmacológico , Hipersensibilidad a los Alimentos/inmunología , RatonesRESUMEN
BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored. METHODS: This study included 10â 794 adults aged ≥18 years from the China National Human Biomonitoring program. Weighted multiple logistic regression and linear regression were used to examine the associations of serum PFAS with hypertension, diastolic blood pressure, and systolic blood pressure. Joint effects of PFAS mixtures on hypertension, diastolic blood pressure, and systolic blood pressure were evaluated using quantile-based g-computation. Additive and multiplicative interactions were used to assess the role of PFAS with testosterone and estradiol on hypertension. RESULTS: The prevalence of hypertension in Chinese adults was 35.50%. Comparing the fourth quartile with the first quartile, odds ratio (95% CI) of hypertension were 1.53 (1.13-2.09) for perfluorononanoic acid, 1.40 (1.03-1.91) for perfluorodecanoic acid, 1.34 (1.02-1.78) for perfluoroheptane sulfonic acid, and 1.46 (1.07-1.99) for perfluorooctane sulfonic acid. Moreover, PFAS mixtures, with perfluorononanoic acid contributing the most, were positively associated with hypertension, diastolic blood pressure, and systolic blood pressure. PFAS and endogenous hormones had an antagonistic interaction in hypertension. For example, the relative excess risk ratio, attributable proportion, and synergy index for perfluorononanoic acid and estradiol were -3.61 (-4.68 to -2.53), -1.65 (-2.59 to -0.71), and 0.25 (0.13-0.47), respectively. CONCLUSIONS: Perfluorononanoic acid, perfluorodecanoic acid, perfluoroheptane sulfonic acid, perfluorooctane sulfonic acid, and PFAS mixtures showed positive associations with hypertension, systolic blood pressure, and diastolic blood pressure. Positive associations of PFAS with hypertension might be attenuated by increased levels of endogenous sex hormones.
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Ácidos Alcanesulfónicos , Fluorocarburos , Hipertensión , Humanos , Fluorocarburos/sangre , Femenino , Hipertensión/epidemiología , Hipertensión/sangre , Masculino , Estudios Transversales , China/epidemiología , Persona de Mediana Edad , Adulto , Ácidos Alcanesulfónicos/sangre , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Exposición a Riesgos Ambientales/efectos adversos , Ácidos Decanoicos/sangre , Disruptores Endocrinos/sangre , Disruptores Endocrinos/efectos adversos , Ácidos Grasos/sangre , Prevalencia , Hormonas Esteroides Gonadales/sangre , Ácidos Sulfónicos/sangre , Contaminantes Ambientales/sangre , Contaminantes Ambientales/efectos adversos , Ácidos Láuricos/sangre , Ácidos Láuricos/farmacologíaRESUMEN
Anti-inflammatory and angiogenesis are two important factors in wound healing. Wound dressings with anti-inflammation and vascularization are essential to address complex interventions, expensive treatments, and uncontrolled release mechanisms. Based on the above considerations, we designed a near-infrared (NIR)-responsive hydrogel dressing, which is composed of mPDA-DFO@LA nanoparticles (mPDA: dopamine hydrochloride nanoparticles, DFO: deferoxamine, LA: lauric acid), valsartan (abbreviated as Va), and dopamine-hyaluronic acid hydrogel. The hydrogel dressing demonstrated injectability, bioadhesive, and photothermal properties. The results indicated the obtained dressing by releasing Va can appropriately regulate macrophage phenotype transformation from M1 to M2, resulting in an anti-inflammatory environment. In addition, DFO encapsulated by LA can be sustainably released into the wound site by NIR irradiation, which further prevents excessive neovascularization. Notably, the results in vivo indicated the mPDA-DFO@LA/Va hydrogel dressing significantly enhanced wound recovery, achieving a healing rate of up to 96% after 11 days of treatment. Therefore, this NIR-responsive hydrogel dressing with anti-inflammation, vascularization, and on-demand programmed drug release will be a promising wound dressing for wound infection.
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Antiinflamatorios , Vendajes , Hidrogeles , Nanocompuestos , Cicatrización de Heridas , Animales , Ratones , Angiogénesis/efectos de los fármacos , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Deferoxamina/química , Deferoxamina/farmacología , Deferoxamina/uso terapéutico , Dopamina/química , Dopamina/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Rayos Infrarrojos , Ácidos Láuricos/química , Ácidos Láuricos/farmacología , Nanocompuestos/química , Nanocompuestos/uso terapéutico , Células RAW 264.7 , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Controlling pathogenic infections while reducing antibiotic usage is an important challenge during poultry production. In addition to vaccination strategies, several solutions to enhance the immune response against pathogens are evaluated. In this study, we aim to determine the effects of the glycerides of lauric acid (GLA) supplementation in chickens' diets on humoral and cellular immune response pathogenic infections, using an in vivo model of infectious bronchitis virus (IBV). One-day-old Ross 308 broilers were vaccinated with live attenuated IBV and fed diets supplemented with or without GLA at 3â¯kg/ton. The levels of early (day 7) specific anti-IBV in sera were significantly increased in broilers fed GLA, compared to the control groups (P<0.05), showing a stronger primary humoral response. The secretion levels of main cytokines remained similar in spleens of all the experimental groups. However, the splenocytes from broilers fed GLA showed higher activation and effector abilities when measured by IFN-γ ELISpot in presence of N-261-280 IBV peptide or Concanavalin A (Con A), a pan T lymphocytes mitogen. In response to N-261-280 peptide, GLA group showed a 2-fold increase of spot numbers (P < 0.05) and 3-fold increase of spot surfaces (P < 0.01) compared to the control groups. Similarly, Con A stimulation showed a 2-fold increases in spot surfaces and numbers in the GLA supplemented group compared to the control group (P < 0.01). In summary, GLA supplementation in chicken feed enhances the primary humoral immune response and strengthen the T lymphocytes mediated cellular immune response. These findings demonstrate how GLA can improve chicken resilience against pathogenic challenges by enhancing their immune responses.
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Pollos , Infecciones por Coronavirus , Suplementos Dietéticos , Inmunidad Celular , Inmunidad Humoral , Virus de la Bronquitis Infecciosa , Ácidos Láuricos , Enfermedades de las Aves de Corral , Animales , Pollos/inmunología , Virus de la Bronquitis Infecciosa/inmunología , Inmunidad Humoral/efectos de los fármacos , Inmunidad Celular/efectos de los fármacos , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/virología , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Ácidos Láuricos/farmacología , Ácidos Láuricos/administración & dosificación , Glicéridos/farmacología , Alimentación Animal/análisis , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Anticuerpos Antivirales/sangre , Dieta/veterinaria , Citocinas/sangreRESUMEN
Osteosarcoma (OS) is a highly malignant primary bone neoplasm that is the leading cause of cancerassociated death in young people. GNE477 belongs to the second generation of mTOR inhibitors and possesses promising potential in the treatment of OS but dose tolerance and drug toxicity limit its development and utilization. The present study aimed to prepare a novel H2O2 stimulusresponsive dodecanoic acid (DA)phenylborate esterdextran (DABDEX) polymeric micelle delivery system for GNE477 and evaluate its efficacy. The polymer micelles were characterized by morphology, size and critical micelle concentration. The GNE477 loaded DABDEX (GNE477@DBD) tumortargeting drug delivery system was established and the release of GNE477 was measured. The cellular uptake of GNE477@DBD by three OS cell lines (MG63, U2OS and 143B cells) was analyzed utilizing a fluorescent tracer technique. The hydroxylated DAB was successfully grafted onto dextran at a grafting rate of 3%, suitable for forming amphiphilic micelles. Following exposure to H2O2, the DABDEX micelles ruptured and released the drug rapidly, leading to increased uptake of GNE477@DBD by cells with sustained release of GNE477. The in vitro experiments, including MTT assay, flow cytometry, western blotting and RTqPCR, demonstrated that GNE477@DBD inhibited tumor cell viability, arrested cell cycle in G1 phase, induced apoptosis and blocked the PI3K/Akt/mTOR cascade response. In vivo, through the observation of mice tumor growth and the results of H&E staining, the GNE477@DBD group exhibited more positive therapeutic outcomes than the free drug group with almost no adverse effects on other organs. In conclusion, H2O2responsive DABDEX presents a promising delivery system for hydrophobic antitumor drugs for OS therapy.
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Dextranos , Peróxido de Hidrógeno , Ácidos Láuricos , Micelas , Osteosarcoma , Animales , Humanos , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Línea Celular Tumoral , Dextranos/química , Ratones , Ácidos Láuricos/química , Ácidos Láuricos/farmacología , Apoptosis/efectos de los fármacos , Polímeros/química , Polímeros/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Ratones Desnudos , Antineoplásicos/farmacología , Antineoplásicos/química , Ratones Endogámicos BALB C , Masculino , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
The current study evaluated the potential enhancement of lauric acid (LA) in black soldier fly, Hermetia illucens, (L.) (Diptera: Stratiomyidae) larvae (BSFL), a source of this short-chain fatty acid which has antimicrobial and immunostimulatory properties. Replicate groups of BSFL were reared on either the coconut or Gainesville diet for 7 days. After the rearing period, BSFL were harvested, purged, dried, and subjected to proximate, fatty acid and amino acid compositions, and pepsin digestibility analyses. Results demonstrate changes in proximate composition. BSFL reared on the coconut had significantly (Pâ =â 0.002) higher lipid content (47.3% vs. 25.2%) on a dry-matter basis. The LA concentration in BSFL produced on the coconut was 31% greater than those reared on Gainesville, resulting in almost 150% more LA. Furthermore, BSFL-fed coconut had reduced crude protein (29.7% of dry weight) and ash (3.7% of dry weight) relative to those fed Gainesville (43.4% and 7.5% for crude protein and ash, respectively) but higher pepsin digestibility (91.0% vs. 87.0%). The relative amounts of various amino acids in the 2 BSFL meals did not differ extensively, with statistically lower concentrations of only phenylalanine and tryptophan and higher concentrations of alanine, arginine, isoleucine, leucine, and serine in BSFL reared on coconut. Results demonstrate that the nutritional composition of BSFL can be manipulated, and an enhancement of LA concentrations of 150% was achieved with coconut, which has value for BSFL as a feed for various livestock, including aquaculture. Lower protein content is a tradeoff in terms of BSFL value as a feed additive.
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Alimentación Animal , Cocos , Dieta , Dípteros , Larva , Ácidos Láuricos , Animales , Larva/crecimiento & desarrollo , Ácidos Láuricos/análisis , Dípteros/crecimiento & desarrollo , Cocos/química , Alimentación Animal/análisisRESUMEN
This research investigated the effect of lecithin on the complexation of lauric acid with maize starch, potato starch, waxy maize starch, and high amylose maize starch. Rapid visco analysis showed that lecithin altered the setback pattern of potato starch-lauric acid and maize starch-lauric acid mixtures but not waxy maize starch-lauric acid. Further investigation, including differential scanning calorimetry, complex index, and X-ray diffraction, showed that lecithin enhanced the complexation of maize starch, potato starch, and high amylose maize starch with lauric acid. Fourier transform infrared and Raman spectroscopy revealed increasingly ordered structures formed in maize starch-lauric acid-lecithin, potato starch-lauric acid-lecithin, and high amylose maize starch-lauric acid-lecithin systems compared to corresponding binary systems. These highly ordered complexes of maize starch, potato starch, and high amylose maize starch also demonstrated greater resistance to in vitro enzymatic hydrolysis. Waxy maize starch complexation however remained unaffected by lecithin. The results of this study show that lecithin impacts complexation between fatty acids and native starches containing amylose, with the starch source being critical. Lecithin minimally impacted the complexation of low amylose starch and fatty acids.