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/metabolismoRESUMEN
BACKGROUND: Sophorolipids are glycolipid biosurfactants with potential antibacterial, antifungal, and anticancer applications, rendering them promising for research. Therefore, this study hypothesizes that sophorolipids may have a notable impact on disrupting membrane integrity and triggering the production of reactive oxygen species, ultimately resulting in the eradication of pathogenic microbes. RESULTS: The current study resulted in the isolation of two Metschnikowia novel yeast strains. Sophorolipids production from these strains reached maximum yields of 23.24 g/l and 21.75 g/l, respectively, at the bioreactors level. Biosurfactants sophorolipids were characterized using FTIR and LC-MS techniques and found to be a mixture of acidic and lactonic forms with molecular weights of m/z 678 and 700. Our research elucidated sophorolipids' mechanism in disrupting bacterial and fungal membranes through ROS generation, confirmed by transmission electron microscopy and FACS analysis. The results showed that these compounds disrupted the membrane integrity and induced ROS production, leading to cell death in Klebsiella pneumoniae and Fusarium solani. In addition, the anticancer properties of sophorolipids were investigated on the A549 lung cancer cell line and found that sophorolipid-11D (SL-11D) and sophorolipid-11X (SL-11X) disrupted the actin cytoskeleton, as evidenced by immunofluorescence microscopy. The A549 cells were stained with Acridine orange/Ethidium bromide, which showed that they underwent necrosis. This was confirmed by flow cytometric analysis using Annexin/PI staining. The SL-11D and SL-11X molecules exhibited low levels of haemolytic activity and in-vitro cytotoxicity in HEK293, Caco-2, and L929 cell lines. CONCLUSION: In this work, novel yeast species CIG-11DT and CIG-11XT, isolated from the bee's gut, produce significant yields of sophorolipids without needing secondary oil sources, indicating a more economical production method. Our research shows that sophorolipids disrupt bacterial and fungal membranes via ROS production. They suggest they may act as chemo-preventive agents by inducing apoptosis in lung cancer cells, offering the potential for enhancing anticancer therapies.
Asunto(s)
Antifúngicos , Antineoplásicos , Metschnikowia , Estrés Oxidativo , Especies Reactivas de Oxígeno , Tensoactivos , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/metabolismo , Humanos , Tensoactivos/farmacología , Tensoactivos/metabolismo , Tensoactivos/química , Estrés Oxidativo/efectos de los fármacos , Antineoplásicos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Células A549 , Metschnikowia/metabolismo , Metschnikowia/efectos de los fármacos , Fusarium/efectos de los fármacos , Fusarium/metabolismo , Klebsiella pneumoniae/efectos de los fármacos , Glucolípidos/farmacología , Glucolípidos/metabolismo , Pruebas de Sensibilidad Microbiana , Ácidos OléicosRESUMEN
Rhamnolipids (RLs) are amphiphilic compounds of bacterial origin that offer a broad range of potential applications as biosurfactants in industry and agriculture. They are reported to be active against different plant pests and pathogens and thus are considered promising candidates for nature-derived plant protection agents. However, as these glycolipids are structurally diverse, little is known about their exact mode of action and, in particular, the relation between molecular structure and biological activity against plant pests and pathogens. Engineering the synthesis pathway in recombinant Pseudomonas putida strains in combination with advanced HPLC techniques allowed us to separately analyze the activities of mixtures of pure mono-RLs (mRLs) and of pure di-RL (dRLs), as well as the activity of single congeners. In a model system with the plant Arabidopsis thaliana and the plant-parasitic nematode (PPN) Heterodera schachtii we demonstrate that RLs can significantly reduce infection, whereas their impact on the host plant varied depending on their molecular structure. While mRLs reduced plant growth even at a low concentration, dRLs showed a neutral to beneficial impact on plant development. Treating plants with dRLs triggered an increased reactive oxygen species (ROS) production, indicating the activation of stress-response signaling and possibly plant defense. Pretreatment of plants with mRLs or dRLs prior to application of flagellin (flg22), a known ROS inducer, further increased the ROS response to flg22. While dRLs stimulated an elevated flg22-induced ROS peak, a pretreatment with mRLs resulted in a prolonged synthesis of ROS indicating a generally elevated stress level. Neither mRLs nor dRLs induced the expression of plant defense marker genes of salicylic acid, jasmonic acid, and ethylene pathways. Detailed studies on dRLs revealed that even high concentrations up to 755 ppm of these molecules have no lethal impact on H. schachtii infective juveniles. Infection assays with individual dRL congeners showed that the C10-C8 acyl chained dRL was the only congener without effect, while dRLs with C10-C12 and C10-C12:1 acyl chains were most efficient in reducing nematode infection even at concentrations below 2 ppm. As determined by phenotyping and ROS measurements, A. thaliana reacted more sensitive to long-chained dRLs in a concentration-dependent manner. Our experiments show a clear structure-activity relation for the effect of RLs on plants. In conclusion, functional assessment and analysis of the mode of action of RLs in plants and other organisms require careful consideration of their molecular structure and composition.
Asunto(s)
Arabidopsis , Glucolípidos , Pseudomonas putida , Arabidopsis/parasitología , Arabidopsis/efectos de los fármacos , Glucolípidos/farmacología , Glucolípidos/metabolismo , Animales , Pseudomonas putida/efectos de los fármacos , Pseudomonas putida/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tylenchoidea/efectos de los fármacos , Enfermedades de las Plantas/parasitología , Enfermedades de las Plantas/microbiologíaRESUMEN
MAIN CONCLUSION: Seed-application of the natural products protects sugar beet and wheat plants against infection with plasmodiophorid-transmitted viruses and thus may represent an efficient, environmentally friendly, easy and cost effective biocontrol strategy. In times of intensive agriculture, resource shortening and climate change, alternative, more sustainable and eco-friendly plant protection strategies are required. Here, we tested the potential of the natural plant substances Glycyrrhiza glabra leaf extract (GE) and the rhamnolipid Rhapynal (Rha) applied to seeds to protect against infection of sugar beet and wheat with soil-borne plant viruses. The soil-borne Polymyxa betae- and Polymyxa graminis-transmitted viruses cause extensive crop losses in agriculture and efficient control strategies are missing. We show that GE and Rha both efficiently protect plants against infection with soil-borne viruses in sugar beet and wheat when applied to seeds. Moreover, the antiviral protection effect is independent of the cultivar used. No protection against Polymyxa sp. was observed after seed treatment with the bio-substances at our analysis time points. However, when we applied the bio-substances directly to soil a significant anti-Polymyxa graminis effect was obtained in roots of barley plants grown in the soil as well as in the treated soil. Despite germination can be affected by high concentrations of the substances, a range of antiviral protection conditions with no effect on germination were identified. Seed-treatment with the bio-substances did not negatively affect plant growth and development in virus-containing soil, but was rather beneficial for plant growth. We conclude that seed treatment with GE and Rha may represent an efficient, ecologically friendly, non-toxic, easy to apply and cost efficient biocontrol measure against soil-borne virus infection in plants.
Asunto(s)
Beta vulgaris , Glycyrrhiza , Enfermedades de las Plantas , Extractos Vegetales , Semillas , Semillas/virología , Semillas/efectos de los fármacos , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/prevención & control , Beta vulgaris/virología , Beta vulgaris/efectos de los fármacos , Extractos Vegetales/farmacología , Triticum/virología , Triticum/efectos de los fármacos , Triticum/crecimiento & desarrollo , Glucolípidos/farmacología , Virus de Plantas/fisiología , Virus de Plantas/efectos de los fármacos , Raíces de Plantas/virología , Raíces de Plantas/efectos de los fármacos , Suelo/química , Microbiología del Suelo , Hordeum/virología , Hordeum/efectos de los fármacos , Plasmodiophorida/fisiología , Plasmodiophorida/efectos de los fármacosRESUMEN
Traumatic spinal cord injury (tSCI) has complex pathophysiological events that begin after the initial trauma. One such event is fibroglial scar formation by fibroblasts and reactive astrocytes. A strong inhibition of axonal growth is caused by the activated astroglial cells as a component of fibroglial scarring through the production of inhibitory molecules, such as chondroitin sulfate proteoglycans or myelin-associated proteins. Here, we used neural precursor cells (aldynoglia) as promoters of axonal growth and a fibrin hydrogel gelled under alkaline conditions to support and guide neuronal cell growth, respectively. We added Tol-51 sulfoglycolipid as a synthetic inhibitor of astrocyte and microglia in order to test its effect on the axonal growth-promoting function of aldynoglia precursor cells. We obtained an increase in GFAP expression corresponding to the expected glial phenotype for aldynoglia cells cultured in alkaline fibrin. In co-cultures of dorsal root ganglia (DRG) and aldynoglia, the axonal growth promotion of DRG neurons by aldynoglia was not affected. We observed that the neural precursor cells first clustered together and then formed niches from which aldynoglia cells grew and connected to groups of adjacent cells. We conclude that the combination of alkaline fibrin with synthetic sulfoglycolipid Tol-51 increased cell adhesion, cell migration, fasciculation, and axonal growth capacity, promoted by aldynoglia cells. There was no negative effect on the behavior of aldynoglia cells after the addition of sulfoglycolipid Tol-51, suggesting that a combination of aldynoglia plus alkaline fibrin and Tol-51 compound could be useful as a therapeutic strategy for tSCI repair.
Asunto(s)
Axones , Fibrina , Ganglios Espinales , Animales , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Ganglios Espinales/citología , Axones/metabolismo , Axones/efectos de los fármacos , Fibrina/metabolismo , Hidrogeles/química , Hidrogeles/farmacología , Ratas , Glucolípidos/farmacología , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Células Cultivadas , Técnicas de Cocultivo , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patología , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Médula Espinal/metabolismo , Médula Espinal/efectos de los fármacos , Médula Espinal/citología , Movimiento Celular/efectos de los fármacosRESUMEN
Following spinal cord injury (SCI), the regenerative capacity of the central nervous system (CNS) is severely limited by the failure of axonal regeneration. The regeneration of CNS axons has been shown to occur by grafting predegenerated peripheral nerves (PPNs) and to be promoted by the transplantation of neural precursor cells (NPCs). The introduction of a combinatorial treatment of PPNs and NPCs after SCI has to address the additional problem of glial scar formation, which prevents regenerating axons from leaving the implant and making functional connections. Previously, we discovered that the synthetic sulfoglycolipid Tol-51 inhibits astrogliosis. The objective was to evaluate axonal regeneration and locomotor function improvement after SCI in rats treated with a combination of PPN, NPC, and Tol-51. One month after SCI, the scar tissue was removed and replaced with segments of PPN or PPN+Tol-51; PPN+NPC+Tol-51. The transplantation of a PPN segment favors regenerative axonal growth; in combination with Tol-51 and NPC, 30% of the labeled descending corticospinal axons were able to grow through the PPN and penetrate the caudal spinal cord. The animals treated with PPN showed significantly better motor function. Our data demonstrate that PPN implants plus NPC and Tol-51 allow successful axonal regeneration in the CNS.
Asunto(s)
Regeneración Nerviosa , Células-Madre Neurales , Nervios Periféricos , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/patología , Ratas , Regeneración Nerviosa/efectos de los fármacos , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/trasplante , Células-Madre Neurales/citología , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/patología , Femenino , Axones/efectos de los fármacos , Glucolípidos/farmacología , Recuperación de la Función/efectos de los fármacosRESUMEN
As a type of biosurfactant, rhamnolipids (RLs) are multifunctional skin-care ingredients, and the molecular interaction of RLs with silk fibroin (SF) is a more complicated process than has long been believed. The interaction and functional properties of them, and their potential as fungicidal agents for agricultural products and as organic preservatives for cosmetics were assessed in this paper. The SF addition makes the RLs aggregation easier through the complexes formation, which decreases the applied concentration of surfactant. The results of spectroscopic analyses and molecular docking suggest that hydrogen bonding and van der Waals forces are significant contributed to the binding mechanism between the two substances. The addition of SF notably enhances the foaming capacity and stability of RLs. The certain antibacterial and antifungal properties of RLs are basically not affected by the SF addition, even the SF-RLS system demonstrates an unobvious synergistic inhibitory impact on Glomerella cingulate (GC). The results offer a theoretical framework for the utilization of RLs as natural fungicides and preservatives in presence of nutritional components, considering the properties of RLs as nontoxic, biodegradable, environmentally friendly, and good compatibility.
Asunto(s)
Antiinfecciosos , Fibroínas , Glucolípidos , Simulación del Acoplamiento Molecular , Glucolípidos/química , Glucolípidos/farmacología , Fibroínas/química , Fibroínas/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/química , Pruebas de Sensibilidad Microbiana , Bacterias/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de Fourier , Hongos/efectos de los fármacos , Tensoactivos/química , Tensoactivos/farmacologíaRESUMEN
The present study evaluates the in-vitro antibiofilm activity against the biofilm formed by Staphylococcus aureus, and the wound-healing efficacy of two different types of rhamnolipids produced by Pseudomonas aeruginosa strain JS29 in S.aureus infected wounds. The biosurfactant production was carried out in a mineral salt medium supplemented with 2 % Glucose and 2 % Glycerol individually and thus were designated as RL-Glu and RL-Gly respectively. 0.5 mg/ml of RL-Glu and RL-Gly demonstrated 90 % growth inhibition of S. aureus while exhibiting bactericidal activity at 4 mg/ml of RL-Glu and 1 mg/ml of RL-Gly. Both types of rhamnolipid cause changes in membrane permeability leading to pathogens' non-viability. 90 % inhibition of biofilm formation by S. aureus was observed at 2 mg/ml of RL-Glu and 0.5 mg/ml of RL-Gly, while 0.5 mg/ml of both rhamnolipid disrupted 90 % of the preformed biofilm. 0.5 mg/ml of RL-Glu and RL-Gly decreases the production of exopolysaccharides and also causes structural alteration. 0.5 mg/ml of RL-Glu and RL-Gly were found to exhibit effective wound healing efficacy in S. aureus infected wounds within 7 days of treatment. Histopathological studies of wound sites revealed efficient wound management by both the rhamnolipid. LCMS and GCMS characterization of the biosurfactant revealed that JS29 produces different rhamnolipid congeners when grown on different carbon sources, thereby influencing the antimicrobial, antibiofilm, and wound healing efficacy of rhamnolipid.
Asunto(s)
Antibacterianos , Biopelículas , Glucolípidos , Pseudomonas aeruginosa , Staphylococcus aureus , Tensoactivos , Cicatrización de Heridas , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Glucolípidos/farmacología , Staphylococcus aureus/efectos de los fármacos , Tensoactivos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Antibacterianos/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Animales , Pruebas de Sensibilidad Microbiana , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Viabilidad Microbiana/efectos de los fármacos , RatonesRESUMEN
Rhamnolipids (RLs) and Fengycins (FGs) are biosurfactants with very promising antifungal properties proposed to reduce the use of synthetic pesticides in crops. They are amphiphilic molecules, both known to target the plasma membrane. They act differently on Botrytis cinerea and Sclerotinia sclerotiorum, two close Sclerotiniaceae phytopathogenic fungi. RLs are more efficient at permeabilizing S. sclerotiorum, and FGs are more efficient at permeabilizing B. cinerea mycelial cells. To study the link between the lipid membrane composition and the activity of RLs and FGs, we analyzed the lipid profiles of B. cinerea and S. sclerotiorum. We determined that unsaturated or saturated C18 and saturated C16 fatty acids are predominant in both fungi. We also showed that phosphatidylethanolamine (PE), phosphatidic acid (PA), and phosphatidylcholine (PC) are the main phospholipids (in this order) in both fungi, with more PA and less PC in S. sclerotiorum. The results were used to build biomimetic lipid membrane models of B. cinerea and S. sclerotiorum for all-atom molecular dynamic simulations and solid-state NMR experiments to more deeply study the interactions between RLs or FGs with different compositions of lipid bilayers. Distinctive effects are exerted by both compounds. RLs completely insert in all the studied model membranes with a fluidification effect. FGs tend to form aggregates out of the bilayer and insert individually more easily into the models representative of B. cinerea than those of S. sclerotiorum, with a higher fluidification effect. These results provide new insights into the lipid composition of closely related fungi and its impact on the mode of action of very promising membranotropic antifungal molecules for agricultural applications.
Asunto(s)
Ascomicetos , Botrytis , Glucolípidos , Lipidómica , Lipopéptidos , Botrytis/efectos de los fármacos , Botrytis/química , Ascomicetos/química , Ascomicetos/efectos de los fármacos , Ascomicetos/metabolismo , Glucolípidos/química , Glucolípidos/farmacología , Glucolípidos/metabolismo , Lipopéptidos/farmacología , Lipopéptidos/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/metabolismo , Lípidos de la Membrana/química , Lípidos de la Membrana/metabolismo , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Membrana Celular/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Materiales Biomiméticos/metabolismoRESUMEN
The use of natural and sustainable additives, that are less aggressive to the environment, is a trend in the food industry. Rhamnolipids (RL) biosurfactants have shown potential for controlling food pathogens however, due to the presence of free carboxyl groups, the pH and ionic strength may influence the properties of such surfactants. In this study, we describe the antimicrobial activity of RL under different pH values and NaCl concentrations, towards both planktonic and biofilms of Listeria monocytogenes. RL were effective at pH 5.0 and the addition of 5 % NaCl improved the bactericidal efficacy for planktonic and sessile cells. The effect of NaCl was more pronounced at pH above 6 showing a significant increase in RL antimicrobial activity. At pH 7.0 planktonic population was eradicated by RL only when salt was present whereas biofilm viability was decreased by 5 log with MBIC varying from > 2500.0 mg/L (RL) to 39.0 mg/L (RL + 5 % NaCl). Larger vesicular and lamellar RL self-assembly structures were predominant when NaCl was present, suggesting their association with the antimicrobial activity observed. The pH and ionic strength of the medium are important parameters to be considered for the development of RL-based strategies to control L. monocytogenes.
Asunto(s)
Biopelículas , Glucolípidos , Listeria monocytogenes , Cloruro de Sodio , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/crecimiento & desarrollo , Concentración de Iones de Hidrógeno , Glucolípidos/farmacología , Glucolípidos/química , Cloruro de Sodio/farmacología , Cloruro de Sodio/química , Concentración Osmolar , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Antibacterianos/farmacología , Tensoactivos/farmacología , Tensoactivos/química , Microbiología de Alimentos , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacosRESUMEN
Invariant natural killer T cell (iNKT) cells produce large amounts of cytokines in response to α-Galactosylceramide (α-GalCer) stimulation. An analog containing two phenyl rings on the acyl chain, C34, was previously found to be more Th1-biased than α-GalCer and triggered greater anticancer activities against breast cancer, melanoma and lung cancer in mice. Since liver is enriched in iNKT cells, we investigated anticancer efficacy of C34 on neuroblastoma with hepatic metastasis. C34 induced Th1-biased cytokine secretions in the liver, significantly suppressed neuroblastoma growth/metastasis and prolonged mouse survival. The anti-tumor efficacy might be attributed to greater expansions of hepatic NKT, NK, CD4+ T, and CD8+ T cells as well as reduction of the number of SSCloGr1intCD11b+ subset of myeloid-derived suppressor cells (MDSCs) in the liver of tumor-bearing mice, as compared to DMSO control group. C34 also upregulated expression of CD1d and CD11c, especially in the SSCloGr1intCD11b+ subset of MDSCs, which might be killed by C34-activated NKT cells, attributing to their reduced number. In addition, C34 also induced expansion of CD4+ T, CD8+ T, and NK cells, which might eliminate neuroblastoma cells. These immune-modulating effects of C34 might act in concert in the local milieu of liver to suppress the tumor growth. Further analysis of database of neuroblastoma revealed that patients with high CD11c expression in the monocytic MDSCs in the tumor had longer survival, suggesting the potential clinical application of C34 for treatment of neuroblastoma.
Asunto(s)
Glucolípidos , Neoplasias Hepáticas , Células T Asesinas Naturales , Neuroblastoma , Animales , Neuroblastoma/patología , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/inmunología , Células T Asesinas Naturales/efectos de los fármacos , Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/secundario , Línea Celular Tumoral , Ratones , Glucolípidos/farmacología , Humanos , Femenino , Citocinas/metabolismo , Células Supresoras de Origen Mieloide/efectos de los fármacos , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Antineoplásicos/farmacología , Galactosilceramidas/farmacologíaRESUMEN
Milk-derived peptides and milk fat globule membrane (MFGM) have gained interest as health-promoting food ingredients. However, the mechanisms by which these nutraceuticals modulate the function of biological systems often remain unclear. We utilized Caenorhabditis elegans to elucidate how MFGM-containing protein powder (MProPow), previously used in a clinical trial, affect the physiology of this model organism. Our results demonstrate that MProPow does not affect lifespan but promotes the fitness of the animals. Surprisingly, gene expression analysis revealed that MProPow decreases the expression of genes functioning on innate immunity, which also translates into reduced survival on pathogenic bacteria. One of the innate immunity-associated genes showing reduced expression upon MProPow supplementation is cpr-3, the homolog of human cathepsin B. Interestingly, knockdown of cpr-3 enhances fitness, but not in MProPow-treated animals, suggesting that MProPow contributes to fitness by downregulating the expression of this gene. In summary, this research highlights the value of C. elegans in testing the biological activity of food supplements and nutraceuticals. Furthermore, this study should encourage investigations into whether milk-derived peptides and MFGM mediate their beneficial effects through the modulation of cathepsin B expression in humans.
Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Suplementos Dietéticos , Glucolípidos , Glicoproteínas , Gotas Lipídicas , Animales , Caenorhabditis elegans/efectos de los fármacos , Glucolípidos/farmacología , Glicoproteínas/farmacología , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Inmunidad Innata/efectos de los fármacos , Catepsina B/metabolismo , Polvos , Proteínas de la Leche/farmacología , Longevidad/efectos de los fármacosRESUMEN
SR9009 is an activator of REV-ERBs with diverse biological activities, including improving exercise tolerance and controlling skeletal muscle mass. To optimise the carbamate motif of SR9009, analogues of SR9009 were synthesised and evaluated. All of them showed REV-ERB-α agonist activities. Among them, 5a, 5f, 5 g, 5m, and 5p showed potencies equivalent to or slightly higher than the potency of SR9009 in vitro. These data indicate that the halogenated benzyl group is an indispensable active group in these compounds. 5m, 5p and SR9009 improved exercise tolerance in normal mice in vivo. Additionally, in hyperlipidemic mice, 5m and 5p not only improved exercise tolerance but also lowered blood lipid levels. 5m and 5p displayed stronger hypoglycaemic activity than SR9009.
Asunto(s)
Glucolípidos , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares , Tiofenos , Animales , Ratones , Tiofenos/farmacología , Tiofenos/química , Tiofenos/síntesis química , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/agonistas , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/metabolismo , Glucolípidos/farmacología , Glucolípidos/química , Glucolípidos/síntesis química , Relación Estructura-Actividad , Masculino , Humanos , Estructura Molecular , Ratones Endogámicos C57BL , Pirrolidinas/farmacología , Pirrolidinas/química , Pirrolidinas/síntesis química , Hipoglucemiantes/farmacología , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Relación Dosis-Respuesta a Droga , Tolerancia al Ejercicio/efectos de los fármacosRESUMEN
Biosurfactants, sustainable alternatives to petrochemical surfactants, are gaining attention for their potential in medical applications. This study focuses on producing, purifying, and characterizing a glycolipid biosurfactant from Candida sp. UFSJ7A, particularly for its application in biofilm prevention on siliconized latex catheter surfaces. The glycolipid was extracted and characterized, revealing a critical micellar concentration (CMC) of 0.98 mg/mL, indicating its efficiency at low concentrations. Its composition, confirmed through Fourier transform infrared spectroscopy (FT-IR) and thin layer chromatography (TLC), identified it as an anionic biosurfactant with a significant ionic charge of -14.8 mV. This anionic nature contributes to its biofilm prevention capabilities. The glycolipid showed a high emulsification index (E24) for toluene, gasoline, and soy oil and maintained stability under various pH and temperature conditions. Notably, its anti-adhesion activity against biofilms formed by Escherichia coli, Enterococcus faecalis, and Candida albicans was substantial. When siliconized latex catheter surfaces were preconditioned with 2 mg/mL of the glycolipid, biofilm formation was reduced by up to 97% for E. coli and C. albicans and 57% for E. faecalis. These results are particularly significant when compared to the efficacy of conventional surfactants like SDS, especially for E. coli and C. albicans. This study highlights glycolipids' potential as a biotechnological tool in reducing biofilm-associated infections on medical devices, demonstrating their promising applicability in healthcare settings.
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Biopelículas , Candida , Catéteres , Glucolípidos , Tensoactivos , Glucolípidos/farmacología , Glucolípidos/química , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Tensoactivos/farmacología , Tensoactivos/química , Candida/efectos de los fármacos , Candida/fisiología , Catéteres/microbiología , Látex/química , Látex/farmacología , Escherichia coli/efectos de los fármacos , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/fisiología , Candida albicans/efectos de los fármacos , Candida albicans/fisiologíaRESUMEN
Acne affects most of the world's population, causing an impact on the self-esteem of adolescents and young adults. One of the causes is the presence of the bacteria Cutibacterium acnes which are part of the natural microbiota of the skin. Topical treatments consist of anti-inflammatory and antibiotics, which could select resistant strains. Alternatives to the antibiotic are biocomposites that have antimicrobial activity like biosurfactants which are produced by bacteria. An innovative way of applying these compounds is bioadhesive polymeric films that adhere to the skin and release the active principle topically. Rhamnolipids have great potential to be used in the treatment of acne because they present antimicrobial activity against C. acnes in low and safe concentrations (MIC of 15.62 µg/mL, CBM of 31.25 µg/mL and CC50 of 181.93 µg/mL). Four films with different rhamnolipids concentrations (0.0; 0.1; 0.2; and 0.3%, w/w) were obtained as to visual appearance, mass variation, thickness, density, solubility, pH, water vapor transmission, mechanical properties (folding endurance, bioadhesion strength, tensile strength, elongation at break and Young's modulus), scanning electron microscopy and infrared. The results show that these formulations had a homogeneous appearance; elastic mechanical properties; pH similar to human skin and bioadhesive. The polymeric films containing rhamnolipids were effective against C. acnes, in the in vitro test, at the three concentrations tested, the film with the highest concentration (0.3%, w/w) being the most promising for presenting the highest antimicrobial activity. Thus, the polymeric film containing rhamnolipids has the potential to be used in the treatment of acne.
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Glucolípidos , Pruebas de Sensibilidad Microbiana , Polímeros , Glucolípidos/química , Glucolípidos/administración & dosificación , Glucolípidos/farmacología , Polímeros/química , Pruebas de Sensibilidad Microbiana/métodos , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/química , Administración Tópica , Propionibacterium acnes/efectos de los fármacos , Acné Vulgar/tratamiento farmacológico , Humanos , Piel/efectos de los fármacos , Solubilidad , Antiinfecciosos/farmacología , Antiinfecciosos/administración & dosificación , Antiinfecciosos/química , Resistencia a la Tracción , Química Farmacéutica/métodosRESUMEN
Leukemia, particularly acute myeloid leukemia (AML) is considered a serious health condition with high prevalence among adults. Accordingly, finding new therapeutic modalities for AML is urgently needed. This study aimed to develop a biocompatible nanoformulation for effective oral delivery of the phytomedicine; baicalin (BAC) for AML treatment. Lipid nanocapsules (LNCs) based on bioactive natural components; rhamnolipids (RL) as a biosurfactant and the essential oil linalool (LIN), were prepared using a simple phase-inversion method. The elaborated BAC-LNCs displayed 61.1 nm diameter and 0.2 PDI. Entrapment efficiency exceeded 98 % with slow drug release and high storage-stability over 3 months. Moreover, BAC-LNCs enhanced BAC oral bioavailability by 2.3-fold compared to BAC suspension in rats with higher half-life and mean residence-time. In vitro anticancer studies confirmed the prominent cytotoxicity of BAC-LNCs on the human leukemia monocytes (THP-1). BAC-LNCs exerted higher cellular association, apoptotic capability and antiproliferative activity with DNA synthesis-phase arrest. Finally, a mechanistic study performed through evaluation of various tumor biomarkers revealed that BAC-LNCs downregulated the angiogenic marker, vascular endothelial growth-factor (VEGF) and the anti-apoptotic marker (BCl-2) and upregulated the apoptotic markers (Caspase-3 and BAX). The improved efficacy of BAC bioactive-LNCs substantially recommends their pharmacotherapeutic potential as a promising nanoplatform for AML treatment.
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Liberación de Fármacos , Flavonoides , Leucemia Mieloide Aguda , Nanocápsulas , Animales , Flavonoides/farmacología , Flavonoides/administración & dosificación , Flavonoides/química , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Nanocápsulas/química , Masculino , Apoptosis/efectos de los fármacos , Ratas , Glucolípidos/química , Glucolípidos/administración & dosificación , Glucolípidos/farmacología , Monoterpenos/farmacología , Monoterpenos/química , Monoterpenos/administración & dosificación , Células THP-1 , Disponibilidad Biológica , Administración Oral , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/química , Ratas Sprague-Dawley , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Monoterpenos AcíclicosRESUMEN
The purpose of this study was to examine whether 4 wk of daily ingestion of milk fat globule membrane (MFGM) combined with exercise training improves physical performance-muscle strength, agility and muscle power-in healthy young adults. The study was designed as a randomized, double-blind, and placebo-controlled trial. Twenty healthy young adults received either an MFGM powder containing 1.6 g of fat and 160 mg of sphingomyelin or an isocaloric placebo powder daily throughout 4 wk of power or agility training. Physical performance tests and body composition measurements were conducted before and after the 4-wk intervention. Ingestion of MFGM did not affect isometric or isokinetic muscle strength, but it was associated with a greater increase in vertical jump peak power compared with placebo. There were no significant changes in body weight or lean body mass during the intervention period in either group, and no significant differences between groups. We conclude that daily MFGM supplementation combined with exercise training has the potential to improve physical performance in young adults; however, further studies with larger sample sizes should be conducted to obtain more evidence supporting achievement of improved physical performance through MFGM supplementation.
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Composición Corporal , Suplementos Dietéticos , Ejercicio Físico , Glucolípidos , Glicoproteínas , Gotas Lipídicas , Fuerza Muscular , Humanos , Método Doble Ciego , Glucolípidos/administración & dosificación , Glucolípidos/farmacología , Glicoproteínas/administración & dosificación , Masculino , Adulto Joven , Femenino , Fuerza Muscular/efectos de los fármacos , Ejercicio Físico/fisiología , Proyectos Piloto , Adulto , Rendimiento Físico Funcional , Peso Corporal , Esfingomielinas/administración & dosificación , Músculo Esquelético/fisiología , Músculo Esquelético/efectos de los fármacosRESUMEN
Ichthyotoxic red tide is a problem that the world is facing and needs to solve. The use of antialgal compounds from marine macroalgae to suppress ichthyotoxic red tide is considered a promising biological control method. Antialgal substances were screened and isolated from Bangia fusco-purpurea, Gelidium amansii, Gloiopeltis furcate, Hizikia fusifarme, Laminaria japonica, Palmaria palmata, and Sargassum sp. to obtain new materials for the development of algaecides against ichthyotoxic red tide microalgae using bioactivity-guided isolation methods. The fractions of seven macroalgae exhibited selective inhibitory activities against Amphidinium carterae and Karenia mikimotoi, of which the ethyl acetate fractions had the strongest and broadest antialgal activities for the two tested red tide microalgae. Their inhibitory effects on A. carterae and K. mikimotoi were even stronger than that of potassium dichromate, such as ethyl acetate fractions of B. purpurea, H. fusifarme, and Sargassum sp. Thin-layer chromatography and ultraviolet spectroscopy were further carried out to screen the ethyl acetate fraction of Sargassum sp. Finally, a new glycolipid derivative, 2-O-eicosanoyl-3-O-(6-amino-6-deoxy)-ß-D-glucopyranosyl-glycerol, was isolated and identified from Sargassum sp., and it was isolated for the first time from marine macroalgae. The significant antialgal effects of 2-O-eicosanoyl-3-O-(6-amino-6-deoxy)-ß-D-glucopyranosyl-glycerol on A. carterae and K. mikimotoi were determined.
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Glucolípidos , Floraciones de Algas Nocivas , Microalgas , Algas Marinas , Algas Marinas/química , Glucolípidos/farmacología , Glucolípidos/aislamiento & purificación , Glucolípidos/química , Floraciones de Algas Nocivas/efectos de los fármacos , Microalgas/química , Dinoflagelados/químicaRESUMEN
Essential oils, well-known for their antifungal properties, are widely utilized to combat fruit decay. However, their application faces big challenges due to their high volatility and hydrophobic traits, which leads to strong odor, short effective time and poor dispersivity. This study aimed to address these challenges by formulating microemulsions consisting of essential oils and rhamnolipids. The optimized microemulsion, featuring a small particle size of 6.8 nm, exhibited higher stability and lower volatility than conventional emulsion. Notably, the prepared microemulsions demonstrated remarkable antimicrobial efficacy against E. coli, S. aureus, C. albicans, S. cerevisiae, and A. niger. The application of these microemulsions proved to be highly effective in preventing blueberry decay while preserving fruit's quality, particularly by minimizing the loss of essential nutrients such as anthocyanins. Consequently, essential oil microemulsions emerge as a highly effective postharvest preservative for fruits, offering a promising solution to extend their shelf life and enhance overall quality.
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Emulsiones , Conservación de Alimentos , Frutas , Glucolípidos , Aceites Volátiles , Aceites Volátiles/química , Aceites Volátiles/farmacología , Frutas/química , Emulsiones/química , Emulsiones/farmacología , Conservación de Alimentos/métodos , Glucolípidos/química , Glucolípidos/farmacología , Arándanos Azules (Planta)/química , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/efectos de los fármacos , Antiinfecciosos/farmacología , Antiinfecciosos/química , Candida albicans/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Conservantes de Alimentos/farmacología , Conservantes de Alimentos/química , Tamaño de la PartículaRESUMEN
Aim: The present study investigated the antimicrobial effectiveness of a rhamnolipid complexed with arginine (RLMIX_Arg) against planktonic cells and biofilms of methicillin-resistant Staphylococcus aureus (MRSA). Methodology: Susceptibility testing was performed using the Clinical & Laboratory Standards Institute protocol: M07-A10, checkerboard test, biofilm in plates and catheters and flow cytometry were used. Result: RLMIX_Arg has bactericidal and synergistic activity with oxacillin. RLMIX_Arg inhibits the formation of MRSA biofilms on plates at sub-inhibitory concentrations and has antibiofilm action against MRSA in peripheral venous catheters. Catheters impregnated with RLMIX_Arg reduce the formation of MRSA biofilms. Conclusion: RLMIX_Arg exhibits potential for application in preventing infections related to methicillin-resistant S. aureus biofilms.
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