RESUMEN

The human milk fat globule membrane (hMFGM) and Lactobacillus modulate the infant's gut and benefit health. Hence, the current study assesses the probiotic potential of Lactiplantibacillus plantarum (MRK3), Limosilactobacillus ferementum (MK1) isolated from infant feces, and its interaction with hMFGM during conditions mimicking infant digestive tract. Both strains showed high tolerance to gastrointestinal conditions, cell surface hydrophobicity, and strong anti-pathogen activity against Staphylococcus aureus. During digestion, hMFGM significantly exhibited xanthine oxidase activity, membrane roughness, and surface topography. In the presence of hMFGM, survival of MRK3 was higher than MK1, and electron microscopic observation revealed successful entrapment of MRK3 in the membrane matrix throughout digestion. Interestingly, probiotic-membrane matrix interaction showed significant synergy to alleviate oxidative stress and damage induced by cell-free supernatant of Escherichia coli in Caco-2 cells. Our results show that a probiotic-encapsulated membrane matrix potentially opens the functional infant formula development pathway.

Asunto(s)

Glucolípidos , Glicoproteínas , Gotas Lipídicas , Leche Humana , Estrés Oxidativo , Probióticos , Humanos , Probióticos/farmacología , Probióticos/química , Gotas Lipídicas/química , Gotas Lipídicas/metabolismo , Glicoproteínas/química , Glicoproteínas/farmacología , Glicoproteínas/metabolismo , Células CACO-2 , Glucolípidos/química , Glucolípidos/farmacología , Glucolípidos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Leche Humana/química , Lactante , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Fórmulas Infantiles/química , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/metabolismo

RESUMEN

Retinal pigment epithelium (RPE) cells derived from induced pluripotent stem cells (iPSCs) serve multiple roles, including among others, modeling RPE development in normal and pathological conditions, investigating mechanisms of RPE physiology, modeling retinal diseases involving the RPE, and developing strategies for regenerative therapies. We have developed a simple and efficient protocol to generate RPE tissue from human iPSCs-derived retinal organoids. The RPE tissue present in the retinal organoids is analogous to the native human RPE in differentiation timeline, histological organization, and key features of functional maturation. Building upon this system, we established a method to generate functionally mature, polarized RPE monolayers comparable to human primary RPE. This comprehensive protocol outlines the steps for isolating and culturing RPE tissue using retinal organoids. The outcome is a pure population of cells expressing mature RPE signatures and organized in a characteristic cobblestone monolayer featuring robust ultrastructural polarization. These RPE monolayers also exhibit the functional hallmarks of bona fide mature RPE cells, providing a suitable system to mimic the biology and function of the native human RPE.

Asunto(s)

Técnicas de Cultivo de Célula , Diferenciación Celular , Células Madre Pluripotentes Inducidas , Organoides , Epitelio Pigmentado de la Retina , Humanos , Epitelio Pigmentado de la Retina/citología , Epitelio Pigmentado de la Retina/metabolismo , Organoides/citología , Organoides/metabolismo , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Técnicas de Cultivo de Célula/métodos , Células Cultivadas

RESUMEN

BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.

Asunto(s)

Angiotensina I , Fragmentos de Péptidos , Fibrosis Pulmonar , Humanos , Angiotensina I/sangre , Masculino , Femenino , Fibrosis Pulmonar/sangre , Fibrosis Pulmonar/diagnóstico , Fragmentos de Péptidos/sangre , Persona de Mediana Edad , Anciano , Estudios Longitudinales , Biomarcadores/sangre , COVID-19/sangre , COVID-19/complicaciones , COVID-19/diagnóstico , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/sangre

RESUMEN

The development and manufacture of high-quality starch are a new research focus in food science. Here, transglutaminase was used in the wet processing of glutinous rice flour to prepare customized sweet dumplings. Transglutaminase (0.2 %) lowered protein loss in wet processing and reduced the crystallinity and viscosity of glutinous rice flour. Moreover, it lowered the cracking and cooking loss of sweet dumplings after freeze-thaw cycles, and produced sweet dumplings with reduced hardness and viscosity, making them more suitable for people with swallowing difficulties. Additionally, in sweet dumplings with 0.2 % transglutaminase, the encapsulation of starch granules by the protein slowed down the digestion and reduced the final hydrolysis rate, which are beneficial for people with weight and glycemic control issues. In conclusion, this study contributes to the production of tasty, customized sweet dumplings.

Asunto(s)

Digestión , Harina , Oryza , Almidón , Transglutaminasas , Oryza/química , Oryza/metabolismo , Transglutaminasas/metabolismo , Transglutaminasas/química , Harina/análisis , Almidón/química , Almidón/metabolismo , Manipulación de Alimentos , Humanos , Viscosidad , Culinaria , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Biocatálisis

RESUMEN

This study examined the impact of live bread yeast (Saccharomyces cerevisiae) on the nutritional characteristics of Asian dried noodles. Micronutrient analysis of fermented noodles revealed a 6.9% increase in the overall amino acid content, a 37.1% increase in the vitamin B content and a 63.0% decrease in the phytic acid level. Molecular weight analysis of starch and protein contents revealed moderate decrease in the fermented noodles. The in vitro digestion of fermented noodles showed a slightly faster initial acidification, four-fold decrease in the initial shear viscosity (from 8.85 to 1.94 Pa·s). The initial large food particle count (>2 mm diameter) was 19.5% lower in the fermented noodles. The fermented noodles contained slightly higher free sugar content (73.5 mg g-1 noodle) during the gastric digestion phase. The overall nutrition and digestion results indicate nutritional improvement and digestion-easing attributes in the fermented noodles.

Asunto(s)

Digestión , Fermentación , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/química , Nutrientes/metabolismo , Nutrientes/análisis , Humanos , Aminoácidos/metabolismo , Aminoácidos/análisis , Pan/análisis , Pan/microbiología , Modelos Biológicos , China , Pueblos del Este de Asia

RESUMEN

High-pressure processing (HPP) of donor human milk (DM) minimally impacts the concentration and bioactivity of some important bioactive proteins including lactoferrin, and bile salt-stimulated lipase (BSSL) compared to Holder pasteurization (HoP), yet the impact of HPP and subsequent digestion on the full array of proteins detectable by proteomics remains unclear. We investigated how HPP impacts undigested proteins in DM post-processing and across digestion by proteomic analysis. Each pool of milk (n = 3) remained raw, or was treated by HPP (500 MPa, 10 min) or HoP (62.5 °C, 30 min), and underwent dynamic in vitro digestion simulating the preterm infant. In the meal, major proteins were minimally changed post-processing. HPP-treated milk proteins better resisted proximal digestion (except for immunoglobulins, jejunum 180 min) and the extent of undigested proteins after gastric digestion of major proteins in HPP-treated milk was more similar to raw (e.g., BSSL, lactoferrin, macrophage-receptor-1, CD14, complement-c3/c4, xanthine dehydrogenase) than HoP.

Asunto(s)

Digestión , Recien Nacido Prematuro , Proteínas de la Leche , Leche Humana , Pasteurización , Proteómica , Humanos , Leche Humana/química , Leche Humana/metabolismo , Proteínas de la Leche/metabolismo , Proteínas de la Leche/química , Proteínas de la Leche/análisis , Presión , Recién Nacido , Lactoferrina/análisis , Lactoferrina/metabolismo , Manipulación de Alimentos , Femenino , Lactante , Modelos Biológicos

RESUMEN

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.

Asunto(s)

Antiinflamatorios , Enfermedades Inflamatorias del Intestino , Polifenoles , Polisacáridos , Polifenoles/química , Polifenoles/farmacología , Polifenoles/administración & dosificación , Humanos , Polisacáridos/química , Polisacáridos/farmacología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Microbioma Gastrointestinal/efectos de los fármacos , Antioxidantes/química , Antioxidantes/farmacología

RESUMEN

Conservation of the genetic diversity through skin and cartilage biobanks represents an essential strategy for maintaining biodiversity. Biobanks for the wild species of the order Rodentia have been little studied. Considering that the cryopreservation technique has specific relationships with the tissue and species of interest, we propose investigating different techniques for preserving tissue integrity and cell viability after cartilage and skin culture from Spix's yellow-toothed cavies. Subsequently, two techniques [solid-surface vitrification (SSV) vs. slow freezing (SF)] were used for cartilage and skin cryopreservation. Tissues not subjected to cryopreservation were used as controls. All tissues were evaluated for morphology and proliferation by histological techniques. Moreover, fragments were cultured, and cells were evaluated for viability, proliferation, metabolism, and apoptosis. Regardless of the cryopreservation technique, no differences were observed for the thickness of the epidermis, dermis, skin, spinous and basal layers, fibroblasts, and proliferative activity regarding the number of nucleolar organizer regions (NOR). SSV ensured better maintenance of epidermal cells, normal chondrocytes, filled gaps, collagen fibers, proliferative activity by NOR area/cell, and reduced perinuclear halos and empty gaps compared to SF. SF ensured the conservation of corneum thickness compared to the control. Although both techniques promoted cell recovery after culture, cells from SF resulted in better subconfluence time and day with cell growth around fragments compared to SSV. In conclusion, both cryopreservation techniques resulted in viable cells after culture. However, SSV promoted better maintenance of tissue morphological integrity, and SF ensured the preservation of all cell quality parameters in Spix's yellow-toothed cavies.

RESUMEN

PURPOSE: To evaluate the effects of 1800 MHz continuous wave (CW) and global system for mobile communications (GSM) modulated radiofrequency electromagnetic field (RFEMF) exposures on signal transduction (ST) protein and cytokine expression in differentiated human-derived monocytic THP-1 cells. MATERIALS AND METHODS: THP-1 cells were differentiated into adherent macrophage-like cells using phorbol 12-myristate 13-acetate (PMA). Following differentiation, cells were exposed to 1800 MHz CW or GSM modulated RFEMF for 0.5, 4, or 24 h at a specific absorption rate (SAR) of 0 (sham) or 2.0 W/kg. Concurrent positive controls (lipopolysaccharide for cytokines; anisomycin for ST proteins) and negative controls were included in each experiment. The expression levels of cytokines (GM-CSF, IFN-γ, IL-1ß, IL-6, IL-10, TNF-α) from culture media and phosphorylated and total ST proteins (CREB, JNK, NF-κB, p38, ERK1/2, Akt, p70S6k, STAT3, STAT5) from cell lysates were assessed using Milliplex magnetic bead array panels. RESULTS: No consistent effect of RFEMF exposure was observed in differentiated THP-1 cells. A statistically significant effect of overall exposure condition was observed for IL-6 with GSM modulation (P = 0.042), but no difference between RFEMF and sham for any exposure condition remained following adjustment for multiple comparisons (P ≥ 0.128). No statistically significant effect of exposure condition was detected for any other cytokine evaluated with either of the RFEMF modulations (P ≥ 0.078). There were no statistically significant changes in expression levels for any of the ST proteins under any studied exposure condition (P ≥ 0.320). CONCLUSIONS: In this study, no evidence of changes were observed in differentiated human derived THP-1 cells following exposure of up to 24 h to 1800 MHz RFEMF at SARs of 0 and 2.0 W/kg on the expression of ST proteins or cytokines.

RESUMEN

Emulsion fortified with ß-carotene was added to corn fiber gum (CFG)/soy protein isolate (SPI) double network gel matrix to obtain emulsion-filled gels (EFG) via dual induction of laccase and glucono-δ-lactone. Protein digestion was accompanied by the release of ß-carotene from gel matrix during in vitro digestion. The surfactant types and corn fiber gum/soy protein isolate ratio affected the ß-carotene bioaccessibility via changing oil-water interfacial composition and emulsion particle size during in vitro digestion. As compared with Tween-20 EFGs, emulsion droplets released from SPI EFGs was more susceptible to flocculation, followed with coalescence due to proteolysis of interfacial SPI during gastric digestion. The resulting oil droplets with large particle size exhibited lower lipase adsorption, thus reducing the free fatty acid content and ß-carotene bioaccessibility. The confocal laser scanning microscope (CLSM) observation confirmed that protein hydrolysate from gel matrix were adsorbed onto the oil-water interface competing with Tween-20 during intestinal digestion. For EFGs with higher CFG content, steric hindrance of CFG molecules and less emulsion release could inhibit droplet flocculation, thus enhancing ß-carotene bioaccessibility.

RESUMEN

Medicinal plants produce specialized metabolites (SM) that are used as drugs. However, due to low yields of field cultivation and the increasing market demand, this production method often failed to meet supply needs. Biotechnological alternatives, such as in vitro plant cultures, offer promising solutions. Nonetheless, SM production in these systems remains too low for industrial exploitation, necessitating an elicitation step to induce the plant defense metabolism. Traditional elicitation methods mimic environmental conditions that trigger plant-specialized metabolism, often with an artificial signal that mimics microbial interaction. Recent insights into the essential role of the plant microbiota, provides new opportunities for elicitation strategies by microbial coculture in a controlled environment. The successful co-culture of in vitro medicinal plants with synthetic microbial communities could enable sustainable production of pharmaceutically important SM.

RESUMEN

Goji berry (Lycium barbarum L.) is a nutrient-rich fruit and has received enormous interest for its health benefits. The beneficial effects of goji berry are linked to the absorption of bioactive compounds within the gastrointestinal digestion process and colon fermentation. Nonetheless, how certain bioactive compounds were released, and metabolism changed of the consumption of whole goji berries were still unclear. Therefore, the present study aimed to evaluate the digestion characteristics of key bioactive compounds in whole goji berries with an in vitro digestion model, and the effects of whole goji berries on the structure of gut microbiota were also investigated. Results showed that a significant release of carbohydrates during the digestion process, peaking within the first 15 min of the intestinal phase (421.4 ± 5.82 mg GE/g, dry weight, respectively), was observed, and the phenolic release reached the highest in the first 15 min of the gastric phase. Meanwhile, the bioaccessibilities of phenolic compounds and carbohydrates were determined to be 63.87% and 80.40%, respectively, after intestinal digestion. In addition, the undigested fractions of goji berries could be further fermented to produce short-chain fatty acids, which decreased the colon pH value (from 7.38 to 6.71) as well as the Firmicutes/Bacteroidetes ratio. Moreover, the goji berries regulated the composition of gut microbiota by promoting beneficial bacteria such as Bacteroides, Parabacteroides, and Paraclostridium, whereas inhibiting the proliferation of harmful bacteria (e.g., Fusobacterium). Our results indicated that the goji berry exhibited significant bioactivity during the digestion and fermentation stage and might provide some new insights into the utilization of goji berries in healthy food processing.

RESUMEN

Hypersensitivity to exogenous or endogenous progesterone presents with a variety of clinical, usually cutaneous, manifestations. The condition can occur at any age during the reproductive years, causes debilitating symptoms and can impact the use of exogenous hormones. Management strategies include symptom control or hormonal manipulation via desensitisation. Strategic testing confirms the diagnosis, while targeted intervention can significantly and positively impact quality of life and further childbearing.

RESUMEN

Fiber dimension, durability/dissolution, and biopersistence are critical factors for the risk of fibrogenesis and carcinogenesis. In the modern era, to reduce, refine, and replace animals in toxicology research, the application of in vitro test methods is paramount for hazard evaluation and designing synthetic vitreous fibers (SVFs) for safe use. The objectives of this review are to: (1) summarize the international frameworks and acceptability criteria for implementation of new approach methods (NAMs), (2) evaluate the adverse outcome pathways (AOPs), key events (KEs), and key event relationships (KERs) for fiber-induced fibrogenesis and carcinogenesis in accordance with Organization for Economic Co-operation and Development (OECD) guidelines, (3) consider existing and emerging technologies for in silico and in vitro toxicity testing for the respiratory system and the ability to predict effects in vivo, (4) outline a recommended testing strategy for evaluating the hazard and safety of novel SVFs, and (5) reflect on methods needs for in vitro in vivo correlation (IVIVC) and predictive approaches for safety assessment of new SVFs. AOP frameworks following the conceptual model of the OECD were developed through an evaluation of available molecular and cellular initiating events, which lead to KEs and KERs in the development of fiber-induced fibrogenesis and carcinogenesis. AOP framework development included consideration of fiber physicochemical properties, respiratory deposition and clearance patterns, biosolubility, and biopersistence, as well as cellular, organ, and organism responses. Available data support that fiber AOPs begin with fiber physicochemical characteristics which influence fiber exposure and biosolubility and subsequent key initiating events are dependent on fiber biopersistence and reactivity. Key cellular events of pathogenic fibers include oxidative stress, chronic inflammation, and epithelial/fibroblast proliferation and differentiation, which ultimately lead to hyperplasia, metaplasia, and fibrosis/tumor formation. Available in vitro models (e.g. single-, multi-cellular, organ system) provide promising NAMs tools to evaluate these intermediate KEs. However, data on SVFs demonstrate that in vitro biosolubility is a reasonable predictor for downstream events of in vivo biopersistence and biological effects. In vitro SVF fiber dissolution rates >100 ng/cm2/hr (glass fibers in pH 7 and stone fibers in pH 4.5) and in vivo SVF fiber clearance half-life less than 40 or 50 days were not associated with fibrosis or tumors in animals. Long (fiber lengths >20 µm) biodurable and biopersistent fibers exceeding these fiber dissolution and clearance thresholds may pose a risk of fibrosis and cancer. In vitro fiber dissolution assays provide a promising avenue and potentially powerful tool to predict in vivo SVF fiber biopersistence, hazard, and health risk. NAMs for fibers (including SVFs) may involve a multi-factor in vitro approach leveraging in vitro dissolution data in complement with cellular- and tissue- based in vitro assays to predict health risk.

RESUMEN

This study aimed to investigate the effects of raw Polygonatum cyrtonema Hua polysaccharides (RPCPs) and "zhi" P. cyrtonema Hua polysaccharides (ZPCPs) on the gluten structure, in vitro digestion, and shelf life of fresh wet noodles (FWN). The results demonstrated that incorporating PCPs improved the cooking and sensory qualities of FWN. Moreover, the shelf life of FWN was extended by 6 days with 1.5 % RPCPs (w/w) compared with the control FWN. Furthermore, incorporating 1.5 % ZPCPs led to a 1.2- and 0.2-fold increase in the disulfide bond and α-helix content, respectively, compared with the control FWN. This resulted in enhanced gluten structure, improved springiness and viscidity, and reduced cooking loss by 14.47 %-52.19 %. The scanning electron microscopy analysis revealed that the starch particles were entrapped by PCPs, leading to higher gelatinization temperature and lower setback value of FWN, thereby reducing the starch digestion ratio to 55.50 %. In summary, the findings suggested that FWN containing PCPs can extend shelf life, improve taste, and slow starch digestion staple.

RESUMEN

Highland barley non-starch polysaccharides (HBNP), particularly ß-glucans, are known for their health-promoting effects, including modulation of glycemic response and enhancement of gut health. This study investigated the impact of different HBNP fractions on the properties and digestibility of high-glycemic index rice starch. HBNP was segmented into five fractions (HBNP-15, HBNP-30, HBNP-45, HBNP-60, and HBNP-75) using gradient ethanol precipitation, and these fractions exhibited varying molecular weights, monosaccharide compositions, and ß-glucan contents. All fractions reduced rice starch's pasting viscosity, with 1 % HBNP-75 leading to a 99.1 % decrease in final viscosity. Morphological and size distribution analyses showed that HBNP fractions limited granule swelling and disrupted starch's continuous phase structure. HBNPs also reduced starch digestibility and increased the formation of resistant starch from 10 % to 28 %. These results suggest potential uses for HBNP fractions in developing low-glycemic starch-based foods.

RESUMEN

Crystalline silica has emerged as a prominent occupational toxicant over extended periods, leading to the development of lung disease and cancer. The objective of this investigation is to establish a benchmark dose (BMD) for crystalline silica micro and nanoparticles based on the dehydrogenase activity of the A549 lung-cell line. The impact of exposure to crystalline silica micro-particles (C-SiO2 MPs) and crystalline silica nanoparticles (C-SiO2 NPs) on A549 epithelial lung cells was examined for durations of 24 and 72 h to evaluate cell viability using the MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay. The determination of dose-response and BMD was carried out through the BMD software v 3.2. The findings reveal a dose-dependent relationship between cell viability and both C-SiO2 MPs and -NPs. The BMDL values for 24 h treatment of C-SiO2 MPs and -NPs were determined to be 2.26 and 0.97 µg/ml, respectively, based on exponential models. Correspondingly, these values were found to be 1.17 and 0.85 µg/ml for the 72 h treatment. This investigation underscores the significance of particle size as a contributing factor in assessing occupational health risks. Moreover, the utilization of BMDL can facilitate the determination of more precise values for occupational exposures by considering various parameters associated with particle presence.

Asunto(s)

Supervivencia Celular , Nanopartículas , Dióxido de Silicio , Dióxido de Silicio/química , Humanos , Células A549 , Nanopartículas/toxicidad , Nanopartículas/química , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Tamaño de la Partícula , Pulmón/efectos de los fármacos , Pulmón/patología , Benchmarking

RESUMEN

Amidst increasing awareness of diet-health relationships, plant-derived bioactive peptides are recognized for their dual nutritional and health benefits. This study investigates bioactive peptides released after Alcalase hydrolysis of protein from chachafruto (Erythrina edulis), a nutrient-rich South American leguminous plant, focusing on their behavior during simulated gastrointestinal digestion. Evaluating their ability to scavenge radicals, mitigate oxidative stress, and influence immune response biomarkers, this study underscores the importance of understanding peptide interactions in digestion. The greatest contribution to the antioxidant activity was exerted by the low molecular weight peptides with ORAC values for the <3 kDa fraction of HES, GD-HES, and GID-HES of 0.74 ± 0.03, 0.72 ± 0.004, and 0.56 ± 0.01 (µmol TE/mg protein, respectively). GD-HES and GID-HES exhibited immunomodulatory effects, promoting the release of NO up to 18.52 and 8.58 µM, respectively. The findings of this study highlighted the potential of chachafruto bioactive peptides in functional foods and nutraceuticals, supporting human health through dietary interventions.

Asunto(s)

Antioxidantes , Digestión , Erythrina , Péptidos , Proteínas de Plantas , Hidrólisis , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Péptidos/química , Péptidos/metabolismo , Erythrina/química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/metabolismo , Humanos , Subtilisinas/metabolismo , Subtilisinas/química , Estrés Oxidativo , Tracto Gastrointestinal/metabolismo

RESUMEN

Milk boasts an array of potent bioactive compounds, such as lactoferrin (Lf), immunoglobulins, and functional proteins, all delivering substantial therapeutic benefits. In this study, Immune Powder (a functional dairy formulation) and its primary component called Fractionated Milk Protein (FMP) containing Lf, zinc, and immunoglobulins and formulated by Ausnutria Pty Ltd. were evaluated for their potential broad-spectrum pharmacological activity. In particular, this study investigated the antibacterial (against pathogenic Escherichia coli), prebiotic (promoting Lactobacillus delbrueckii growth), anti-inflammatory (inhibition of NO production in RAW264.7 macrophages), and antiviral (against human coronavirus 229E) effects of the samples. In addition, the impact of simulated gastric digestion on the efficacy of the samples was explored. LCMS-based proteomics was implemented to unveil cellular and molecular mechanisms underlying antiviral activity. The Immune Powder demonstrated antibacterial activity against E. coli (up to 99.74 ± 11.47% inhibition), coupled with prebiotic action (10.84 ± 2.2 viability fold-change), albeit these activities diminished post-digestion (p < 0.01). The Immune Powder effectively mitigated NO production in lipopolysaccharide-stimulated RAW264.7 macrophages, with declining efficacy post-digestion (p < 0.0001). The Immune Powder showed similar antiviral activity before and after digestion (p > 0.05) with up to 3-fold improvement. Likewise, FMP exhibited antibacterial potency pre-digestion at high concentrations (95.56 ± 1.23% inhibition at 125 mg/mL) and post-digestion at lower doses (61.82 ± 5.58% inhibition at 3906.25 µg/mL). FMP also showed enhanced prebiotic activity post-digestion (p < 0.0001), NO inhibition pre-digestion, and significant antiviral activity. The proteomics study suggested that the formulation and its primary component shared similar antiviral mechanisms by inhibiting scavenger receptor binding and extracellular matrix interaction.

Asunto(s)

Polvos , Probióticos , Animales , Ratones , Probióticos/farmacología , Células RAW 264.7 , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Antivirales/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Antibacterianos/farmacología , Proteínas de la Leche/farmacología , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Óxido Nítrico/metabolismo , Prebióticos , Productos Lácteos/microbiología , Coronavirus/efectos de los fármacos

RESUMEN

Darolutamide is a potent second-generation, selective nonsteroidal androgen receptor inhibitor (ARI), which has been approved by the US Food and Drug Administration (FDA) in treating castrate-resistant, non-metastatic prostate cancer (nmCRPC). Whether darolutamide affects the activity of UDP-glucuronosyltransferases (UGTs) is unknown. The purpose of the present study is to evaluate the inhibitory effect of darolutamide on recombinant human UGTs and pooled human liver microsomes (HLMs), and explore the potential for drug-drug interactions (DDIs) mediated by darolutamide through UGTs inhibition. The product formation rate of UGTs substrates with or without darolutamide was determined by HPLC or UPLC-MS/MS to estimate the inhibitory effect and inhibition modes of darolutamide on UGTs were evaluated by using the inhibition kinetics experiments. The results showed that 100 µM darolutamide exhibited inhibitory effects on most of the 12 UGTs tested. Inhibition kinetic studies of the enzyme revealed that darolutamide noncompetitively inhibited UGT1A1 and competitively inhibited UGT1A7 and 2B15, with the Ki of 14.75 ± 0.78 µM, 14.05 ± 0.42 µM, and 6.60 ± 0.08 µM, respectively. In particular, it also potently inhibited SN-38, the active metabolite of irinotecan, glucuronidation in HLMs with an IC50 value of 3.84 ± 0.46 µM. In addition, the in vitro-in vivo extrapolation (IVIVE) method was used to quantitatively predict the risk of darolutamide-mediated DDI via inhibiting UGTs. The prediction results showed that darolutamide may increase the risk of DDIs when administered in combination with substrates of UGT1A1, UGT1A7, or UGT2B15. Therefore, the combined administration of darolutamide and drugs metabolized by the above UGTs should be used with caution to avoid the occurrence of potential DDIs.