The role and mechanism of citrus flavonoids in cardiovascular diseases prevention and treatment.

Cardiovascular diseases (CVDs) have been ranked as the leading cause of death in the world, whose global incidence is increasing year by year. Citrus, one of the most popular fruits in the world, is rich in flavonoids. Citrus flavonoids attract special attention due to a variety of biological activities, especially in the prevention and treatment of CVDs. The research progress of citrus flavonoids on CVDs have been constantly updated, but relatively fragmented, which needed to be systematically summarized. Hence, the recent research about citrus flavonoids and CVDs were reviewed, including the types and in vivo processes of citrus flavonoids, epidemiology study and mechanism on prevention and treatment of CVDs by citrus flavonoids. This review would provide a theoretical basis for the citrus flavonoids research and a new idea in the citrus industry development and application.

Nobiletin mitigates NAFLD via lipophagy and inflammation.

Nonalcoholic fatty liver disease (NAFLD), an increasingly serious health issue around the world, is characterized as a lipid metabolic disorder without any satisfactory treatment. Nobiletin (NOB), a citrus flavonoid, is considered a promising candidate for NAFLD prevention although there is limited research towards its exact mechanism. In this study, the preventative effect of NOB on NAFLD was investigated using high fat diet-fed ApoE-/- mice and free fatty acid-treated HepG2 cells. The results of hematoxylin and eosin staining of liver sections revealed that L-NOB (50 mg kg-1 d-1 NOB), M-NOB (100 mg kg-1 d-1 NOB) and H-NOB (200 mg kg-1 d-1 NOB) could significantly ameliorate NAFLD. Further exploration illustrated that NOB alleviated hepatic steatosis mainly via TFEB-mediated lysosomal biogenesis and lipophagy. Besides, NOB could mitigate NLRP3 inflammasome assembly and modulate M1/M2 macrophage polarization in vivo and in vitro. The mechanisms above allowed NOB to attenuate NAFLD, but their close association needed further investigation. Our research not only illustrated NOB as a potential candidate for NAFLD prevention, but also provided new insight into the pathogenic mechanisms of NAFLD development.

Ethanol inhibits persistent activity in prefrontal cortical neurons.

Cognitive functions supported by neurons in the prefrontal cortex (PFC) are disrupted by acute and chronic exposure to alcohol, yet little is known about the mechanisms that underlie these effects. In the present study, in vivo and in vitro electrophysiology was used to determine the effects of ethanol on neuronal firing and network patterns of persistent activity in PFC neurons. In vivo, ethanol (0.375-3.5 g/kg) dose-dependently reduced spike activity in the PFC measured with multielectrode extracellular recording in the anesthetized rat. In an in vitro coculture system containing slices of PFC, hippocampus, and ventral tegmental area (VTA), ethanol (25-100 mM) decreased persistent activity of PFC neurons, but had little effect on firing evoked by direct current injection. Persistent activity was often enhanced after ethanol washout and this effect was maintained in cultures lacking the VTA. A low concentration of the NMDA antagonist APV (5 microM) mimicked the inhibition of ethanol of persistent activity with no change in activity after washout. Ethanol inhibition of spontaneous and VTA-evoked persistent activity was enhanced by the D1 dopamine receptor antagonist SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride]. The results of this study show that ethanol inhibits persistent activity and spike firing of PFC neurons and that the degree of ethanol inhibition may be influenced by D1 receptor tone. Ethanol-induced alterations in the activity of deep-layer cortical neurons may underlie some of the behavioral effects associated with ethanol intake.

[Changes in electrophysiological and morphological properties of neurons during the development of the visual cortex in the rat].

To investigate the intracellular mechanism of activity-dependent synapses formation and redistribution, we studied the electrophysiological and morphological characteristics of neurons of the developing visual cortex, and observed the level of synchronism of age and changes in the properties. Whole cell patch-clamp recordings and intracellular biocytin staining were used to record postsynaptic currents (PSCs) from neurons in the visual cortex of Sprague-Dawley rats (postnatal d 4-28). The histological processing was made. There were three types of PSCs in 156 cells: silent response, monosynaptic response and polysynaptic response, during the first developmental month. Before eyes opened the number of the neurons with the silent response (57.3%) was significantly higher than that after the eyes opened (11.9%) (P<0.001). However, the incidence of polysynaptic PSCs increased from 12.4% before eyes opened to 28.9% after eyes opened (P<0.01). During postnatal week 1, all cells were classified as immature. The immature cells had very high input resistances (R(N)>1.0 G Omega), low amplitude (-0.87 mA) and short decay time (-0.98 ms). During postnatal week 4, all cells were mature with lower input resistance (R(N)<310 M Omega), larger amplitude (-66 mA), and longer decay time (-225 ms). From postnatal weeks 1 to 3, the cells had electrophysiological properties that were intermediate between the immature and mature types of cells. With biocytin intracellular staining, five types of neurons were obtained: pyramidal cells, satellite cells, basket cells, neuroglial cells and immature cells. On the basis of their electrophysiological and morphological characteristics, pyramidal cells were classified into three categories: immature, intermediate, and mature cell types. During postnatal week 1, cells were immature with very high input resistance. Morphologically immature cells had short simple dendritic arborizations which incompletely penetrated the layer where the cell body lies. From postnatal weeks 2 to 4, the cells were mature with low input resistance. They were morphologically more complex with dendritic arborizations which completely penetrated the whole layers of the visual cortex. From postnatal weeks 1 to 2, a third, intermediate cell type had electrophysiological properties that were intermediate between the immature and mature cell types. Three distinctive types of pyramidal cells in visual cortex only co-exist during postnatal weeks 1 to 2. Data show that activity-dependent synapes are formed and integrated into local neuronal networks with visual stimulation. In the critical period of visual development, the level of synchronism of age and changes in electrophysiological and morphological properties in the visual cortex is higher than that in the subcortex.