RESUMEN
Early intervention using dietary supplements may be effective in alleviating cognitive impairment among individuals with mild cognitive impairment (MCI). This study investigated the efficacy and safety of Lactobacillus plantarum C29-fermented soybean (DW2009) as a nutritional supplement for cognitive enhancement. One hundred individuals with MCI were randomly assigned to take DW2009 (800 mg/day, n = 50) or placebo (800 mg/day, n = 50) for 12 weeks. The primary outcome measure was change in the composite score of cognitive functions related to memory and attention, measured by computerized neurocognitive function tests. Associations between changes in serum brain-derived neurotrophic factor (BDNF) levels and cognitive performance for each treatment group were evaluated. Compared to the placebo group, the DW2009 group showed greater improvements in the combined cognitive functions (z = 2.36, p for interaction = 0.02), especially in the attention domain (z = 2.34, p for interaction = 0.02). Cognitive improvement was associated with increased serum BDNF levels after consumption of DW2009 (t = 2.83, p = 0.007). The results of this clinical trial suggest that DW2009 can be safely administered to enhance cognitive function in individuals with MCI. Increased serum BDNF levels after administering DW2009 may provide preliminary insight into the underlying effects of cognitive improvement, which suggests the importance of the gut-brain axis in ameliorating cognitive deficits in MCI.
Asunto(s)
Disfunción Cognitiva/dietoterapia , Lactobacillus plantarum , Probióticos/uso terapéutico , Alimentos de Soja , Anciano , Factor Neurotrófico Derivado del Encéfalo/sangre , Disfunción Cognitiva/fisiopatología , Método Doble Ciego , Heces/microbiología , Femenino , Microbioma Gastrointestinal , Humanos , Masculino , Persona de Mediana Edad , Probióticos/efectos adversos , Resultado del TratamientoRESUMEN
Artemin, one of the glial cell line-derived neurotrophic factor (GDNF) family, enhances the generation and survival of early sympathetic neurons and superior cervical ganglion (SCG) neurons. Src-family kinases (SFK) are involved in the growth and differentiation of cells, which are composed of unique Src homology 2 (SH2), Src homology 3 (SH3) and kinase domains. Various extra-cellular molecules containing growth factors and G-protein coupled receptors stimulate SFK. In this report, artemin is shown to have a significant effect on the neurite growth of dorsal root ganglia (DRG) neurons. Also, artemin triggers Src-family kinase activation and the phosphorylation of extra-cellular signal-regulated kinases (ERK) mitogen-activated protein kinase (MAPK). Artemin also regulated actin polymerization. There are several indications that another SH3-containing protein, Hck, and an SH3-containing adaptor protein, Nck1, play an important role in the organization of the actin cytoskeleton by cellular signalling. These findings suggest that the exploration of binding partners for the SH3 domain could provide an insight into regulation between the microtubule and actin networks. The binding partners for the SH3 domains of Nck, Src and Hck that we identified were Smc chromosome segregation ATPases, FOG Zn-finger protein and the FYVE zinc-binding domain, respectively.
Asunto(s)
Axones/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ganglios Espinales/metabolismo , Proteínas del Tejido Nervioso/fisiología , Neuronas/metabolismo , Familia-src Quinasas/metabolismo , Actinas/metabolismo , Animales , Axones/efectos de los fármacos , Células Cultivadas , Ganglios Espinales/citología , Humanos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas del Tejido Nervioso/farmacología , Neuronas/citología , Neuronas/efectos de los fármacos , Fosforilación , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Dominios Homologos src/fisiologíaRESUMEN
Three new flavonoid glycosides ( 1- 3), 11-hydroxyhainanolidol ( 4), and a new dibenzylbutyrolactone lignan glycoside ( 5) were isolated from the aerial parts of Cephalotaxus koreana Nakai, along with 19 known flavonoids. The structures of the new compounds were elucidated using spectroscopic evidence, primarily NMR and MS. Twenty-four compounds were isolated, and among these isoscutellarein 5-O-beta-D-glucopyranoside ( 3), apigenin ( 6), kaempferol 3-O-alpha-L-rhamnopyranosyl(1'''-->6'')-beta-D-glucopyranoside ( 7), tamarixetin 3-O-alpha-L-rhamnopyranosyl(1'''-->6'')-beta-D-glucopyranoside ( 8), quercetin 3-O-[6''-O-acetyl]-beta-D-glucopyranoside ( 9), and quercetin 3-O-alpha-L-rhamnopyranoside ( 10) showed significant inhibitory activities against osteoclast differentiation at concentrations of 0.1 and 1.0 microg/mL.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Cephalotaxus/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Glucósidos/aislamiento & purificación , Glucósidos/farmacología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Plantas Medicinales/química , Relación Dosis-Respuesta a Droga , Flavonoides/química , Glucósidos/química , Glicósidos , Corea (Geográfico) , Estructura Molecular , Osteoclastos/citologíaRESUMEN
The 24.5 kDa ribosomal protein L10 (RP-L10), which was encoded by QM gene, was known to interact with the SH3 domain of Yes kinase. Herein, we demonstrate that RP-L10 interacts with the SH3 domain of Src and activates the binding of the Nck1 adaptor protein with skeletal proteins such as the Wiskott-Aldrich Syndrome Protein (WASP) and WASP interacting protein (WIP) in neuroblastoma cell line, SH-SY-5y. The RP-L10 was associated with the SH3 domains of Src and Yes. It is shown that two different regions of RP-L10 are associated with the Src-SH3. The effect of ectopic RP-L10 expression on neuronal cell scaffolding was explored in cells transiently transfected with QM. SH-SY-5y human neuroblastoma cells transfected with QM were considerably more susceptible to neurite outgrowth induced by glial cell line-derived neurotrophic factor (GDNF). However, RP-L10 did not directly interact with actin assembly. Taken together, these results suggest that the RP-L10 may positively regulate the GDNF/Ret-mediated signaling of neurite outgrowth in the neuroblastoma cell line, SH-SY-5y.