RESUMEN
Several studies have documented the interaction between the immune and endocrine systems as an effective defense strategy against tuberculosis, involving the production of several molecules and immunological processes. In this study, we determined the effect of cortisol and dehydroepiandrosterone (DHEA) on the production of antimicrobial peptides such as cathelicidin and human ß-defensin (HBD) -2, and HBD-3 and their effect on intracellular growth of Mycobacterium tuberculosis (Mtb) in lung epithelial cells and macrophages. Our results showed that DHEA promotes the production of these antimicrobial peptides in infected cells, correlating with the decrease of Mtb bacilli loads. These results suggest the use of exogenous DHEA as an adjuvant for tuberculosis therapy.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/biosíntesis , Deshidroepiandrosterona/farmacología , Hidrocortisona/farmacología , Mycobacterium tuberculosis , beta-Defensinas/biosíntesis , Células A549 , Células Epiteliales/microbiología , Humanos , Macrófagos/microbiología , Células THP-1 , CatelicidinasRESUMEN
The negative association between protein and oil production in soybean (Glycine max) seed is well-documented. However, this inverse relationship is based primarily on the composition of mature seed, which reflects the cumulative result of events over the course of soybean seed development and therefore does not convey information specific to metabolic fluctuations during developmental growth regimes. In this study, we assessed maternal nutrient supply via measurement of seed coat exudates and metabolite levels within the cotyledon throughout development to identify trends in the accumulation of central carbon and nitrogen metabolic intermediates. Active metabolic activity during late seed development was probed through transient labeling with 13C substrates. The results indicated: (1) a drop in lipid contents during seed maturation with a concomitant increase in carbohydrates, (2) a transition from seed filling to maturation phases characterized by quantitatively balanced changes in carbon use and CO2 release, (3) changes in measured carbon and nitrogen resources supplied maternally throughout development, (4) 13C metabolite production through gluconeogenic steps for sustained carbohydrate accumulation as the maternal nutrient supply diminishes, and (5) oligosaccharide biosynthesis within the seed coat during the maturation phase. These results highlight temporal engineering targets for altering final biomass composition to increase the value of soybeans and a path to breaking the inverse correlation between seed protein and oil content.
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Carbono/metabolismo , Glycine max/metabolismo , Nitrógeno/metabolismo , Proteínas de Plantas/metabolismo , Semillas/metabolismo , Biomasa , Metabolismo de los Hidratos de Carbono , Dióxido de Carbono/metabolismo , Isótopos de Carbono , Cotiledón/crecimiento & desarrollo , Cotiledón/metabolismo , Metabolismo de los Lípidos , Oligosacáridos/biosíntesis , Aceites de Plantas/metabolismo , Semillas/crecimiento & desarrollo , Glycine max/crecimiento & desarrolloRESUMEN
N,N-dimethyltryptamine (DMT) is a component of the ayahuasca brew traditionally used for ritual and therapeutic purposes across several South American countries. Here, we have examined, in vitro and vivo, the potential neurogenic effect of DMT. Our results demonstrate that DMT administration activates the main adult neurogenic niche, the subgranular zone of the dentate gyrus of the hippocampus, promoting newly generated neurons in the granular zone. Moreover, these mice performed better, compared to control non-treated animals, in memory tests, which suggest a functional relevance for the DMT-induced new production of neurons in the hippocampus. Interestingly, the neurogenic effect of DMT appears to involve signaling via sigma-1 receptor (S1R) activation since S1R antagonist blocked the neurogenic effect. Taken together, our results demonstrate that DMT treatment activates the subgranular neurogenic niche regulating the proliferation of neural stem cells, the migration of neuroblasts, and promoting the generation of new neurons in the hippocampus, therefore enhancing adult neurogenesis and improving spatial learning and memory tasks.
Asunto(s)
Banisteriopsis , Células-Madre Neurales , Animales , Ratones , N,N-Dimetiltriptamina , Neurogénesis , TéRESUMEN
The plant kingdom produces a variety of fatty acid structures, many of which possess functional groups useful for industrial applications. The species that produce these unusual fatty acids are often not suitable for large scale commercial production. The ability to create genetically modified plants, together with emerging synthetic biology approaches, offers the potential to develop alternative oil seed crops capable of producing high levels of modified lipids. In some cases, by combining genes from different species, non-natural lipids with a targeted structure can be conceived. However, the expression of the biosynthetic enzymes responsible for the synthesis of unusual fatty acids typically results in poor accumulation of the desired product. An improved understanding of fatty acid flux from synthesis to storage revealed that specialized enzymes are needed to traffic unusual fatty acids. Co-expression of some of these additional enzymes has incrementally increased the levels of unusual fatty acids in transgenic seeds. Understanding how the introduced pathways interact with the endogenous pathways will be important for further enhancing the levels of unusual fatty acids in transgenic plants. Eliminating endogenous activities, as well as segregating the different pathways, represent strategies to further increase accumulation of unusual lipids.
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Metabolismo de los Lípidos , Ingeniería Metabólica , Aceites de Plantas/metabolismo , Biología Sintética , Productos Agrícolas , Ácidos Grasos/metabolismo , Plantas Modificadas Genéticamente , Semillas/genética , Semillas/metabolismo , Triglicéridos/metabolismoRESUMEN
BACKGROUND: Calcitriol (vitamin D) supplementation has been proposed for therapeutical use in vascular diseases due to its immunomodulatory activity, preventing inflammation and promoting angiogenesis. In the present study, we hypothesised whether calcitriol downregulates pro-inflammatory gene expression without affecting angiogenesis and anti-inflammatory gene expression in LPS-induced endothelial cells. METHOD: In order to evaluate the effect of calcitriol in suppressing inflammatory gene expression in the endothelium, endothelial cells were exposed to the physiological concentration of calcitriol followed by stimulation with lipopolysaccharide (LPS). Gene expression of interleukin (IL)-1ß, Transforming Growth Factor (TGF)-ß, Human ß-defensin (HBD)-2, angiogenin (ANG) and cathelicidin (LL-37) were quantified by quantitative polymerase chain reaction. RESULTS: The results from six independent experiments conducted in duplicate, showed that calcitriol decreased IL-1ß (p < 0.01) and HBD-2 expression (p < 0.01) when compared to non-treated cells. However, calcitriol treatment had no effect on TGF-ß, ANG and LL-37 gene expression. CONCLUSION: Calcitriol prevents inflammatory gene expression, but does not affect expression of angiogenic genes in endothelial cells, which suggest the potential use of calcitriol to prevent endothelial activation through the downregulation of IL-1ß and HBD-2.
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Calcitriol/administración & dosificación , Citocinas/inmunología , Células Endoteliales/inmunología , Regulación de la Expresión Génica/inmunología , Inflamación/inmunología , Inflamación/prevención & control , Antiinflamatorios/administración & dosificación , Línea Celular , Relación Dosis-Respuesta a Droga , Células Endoteliales/efectos de los fármacos , Sangre Fetal/citología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Mediadores de Inflamación/inmunologíaRESUMEN
Carotenoids are health-promoting organic molecules that act as antioxidants and essential nutrients. We show that chickens raised on a diet enriched with an engineered corn variety containing very high levels of four key carotenoids (ß-carotene, lycopene, zeaxanthin and lutein) are healthy and accumulate more bioavailable carotenoids in peripheral tissues, muscle, skin and fat, and more retinol in the liver, than birds fed on standard corn diets (including commercial corn supplemented with colour additives). Birds were challenged with the protozoan parasite Eimeria tenella and those on the high-carotenoid diet grew normally, suffered only mild disease symptoms (diarrhoea, footpad dermatitis and digital ulcers) and had lower faecal oocyst counts than birds on the control diet. Our results demonstrate that carotenoid-rich corn maintains poultry health and increases the nutritional value of poultry products without the use of feed additives.
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Carotenoides/farmacocinética , Carotenoides/uso terapéutico , Coccidiosis/tratamiento farmacológico , Coccidiosis/prevención & control , Aves de Corral/parasitología , Zea mays/química , Animales , Disponibilidad Biológica , Pollos , Coccidiosis/parasitología , Dermatitis/complicaciones , Dermatitis/patología , Dieta , Eimeria/efectos de los fármacos , Heces/parasitología , Hígado/efectos de los fármacos , Hígado/metabolismo , Plantas Modificadas Genéticamente , Úlcera/complicaciones , Úlcera/patología , Vitamina A/farmacologíaRESUMEN
Long-term diagnosed and treated HIV-infected patients have to cope with a wide range of challenges that threaten their ability to age successfully. We report the results of a randomized controlled trial testing the effects of a mindfulness-based cognitive therapy (MBCT) program on quality of life (QoL), emotional status, and immune status over a 3-month period. Forty HIV-infected patients diagnosed prior to 1996 and on cART for a minimum of 5 years were randomized to follow an MBCT program (n = 20) or remain as controls (routine follow-up) (n = 20). A regression analysis was performed, and the measurement of effect size was estimated using Cohen's d. QoL, psychological stress, depressive symptoms, and anxiety symptoms improved in the MBCT group compared with the control group. During follow-up, patients in the MBCT group had a significantly increased CD4 cell count. Effect sizes for MBCT on the variables assessed were large (d = 0.8). The findings suggest that this program may help to promote successful aging in these patients.