EoL-1 cells differentiate into eosinophils in the presence of n-butyrate, but the mechanism has remained to be elucidated. Because n-butyrate can inhibit histone deacetylases, we hypothesized that the inhibition of histone deacetylases induces the differentiation of EoL-1 cells into eosinophils. In this study, using n-butyrate and two other histone deacetylase inhibitors, apicidin and trichostatin A, we have analyzed the relationship between the inhibition of histone deacetylases and the differentiation into eosinophils in EoL-1 cells. It was demonstrated that apicidin and n-butyrate induced a continuous acetylation of histones H4 and H3, inhibited the proliferation of EoL-1 cells, and induced the expression of markers for mature eosinophils such as integrin , CCR1, and CCR3 on EoL-1 cells, while trichostatin A evoked a transient acetylation of his tones and induced no differentiation into eosinophils. These findings suggest that the continuous inhibition of histone deacetylases in EoL-1 cells induces the differentiation into mature eosinophils.

Synaptic plasticity, which is a long lasting change in synaptic efficacy, underlies many neural processes like learning and memory. It has long been acknowledged that new protein synthesis is essential for both the expression of synaptic plasticity and memory formation and storage. Most of the research interests in this field have focused on the events regulating transcriptional activation of gene expression from the cell body and nucleus. Considering extremely differentiated structural feature of a neuron in CNS, a neuron should meet a formidable task to overcome spatial and temporal restraints to deliver newly synthesized proteins to specific activated synapses among thousands of others, which are sometimes several millimeters away from the cell body. Recent advances in synaptic neurobiology has found that almost all the machinery required for the new protein translation are localized inside or at least in the vicinity of postsynaptic compartments. These findings led to the hypothesis that dormant mRNAs are translationally activated locally at the activated synapse, which may enable rapid and delicate control of new protein synthesis at activated synapses. In this review, we will describe the mechanism of local translational control at activated synapses focusing on the role of cytoplasmic polyadenylation of dormant mRNAs.

The main aim of this study was to characterize the pharmacological profile of flavonoids utilizing behavioral tests and to investigate how the psychopharmacological activities of wogonin, baicalein and oroxylin A are different. Wogonin, baicalein and oroxylin A were intraperitoneally injected as dosages of 2.5, 5, 10 and 20 mg/kg. In the locomotor activity, Rota-rod test, and elevated plus-maze tests, the behavioral parameters were analyzed by automatic systems. Thiopental induced sleeping time was measured. Water extract of S. baicalensis didn't exhibit sedative effect. Wogonin and bacalein exhibited anxiolytic activity although it was less potent than buspirone. Wogonin and baicalein decreased locomotor activity at a dose of 10 mg/kg. Wogonin also shortened significantly running time on the rota-rod at doses of 5 and 10 mg/kg. Wogonin and baicalein enhanced sleeping at doses of 5 and 10 mg/kg. These results indicate that wogonin produce anxiolysis with sedation and so did bacalein with mild sedation. On the contrary, oroxylin A enhanced running activity on the rotarod and did't depress locomotor activity. Oroxylin A significantly hindered sleeping rather than helped it at doses of 5 and 10 mg/kg. Oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This study demonstrates that wogonin and bacalein exhibited anxiolytic activity with mild sedation, but oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This result indicates that anxiolytic effect without sedation induced by Scutellaria baicalensis is produced by combination of flavonoids.

CKD-602 exerts its antitumor effect via inhibition of topoisomerase I in cancer cells. Multicellular spheroid (MCS) and Multicellular layers (MCLs) are known as in vitro 3-dimensional models which closely represent tumor conditions in vivo. In order to investigate the potential of CKD-602 against human colorectal tumors, we evaluated the anti-proliferative activity and penetration ability of CKD-602 in MCS and MCL cultures of DLD-l human colorectal cancer cells, respectively. The maximum effects() induced by CKD-602 were significantly lower in MCS compared to monolayers (48% vs 92%). With prolonged drug exposure, the of CKD-602 decreased to in monolayers after 24 h exposure and in MCS after 6 days, respectively. However, no further increase in effect was observed for exposure time longer than growth doubling time (Td) in both cultures. Activity of CKD-602 was significantly reduced after penetration through MCL and also with cell-free insert membrane. In conclusion, CKD-602 showed significantly decreased anti-proliferative activity in 3D cultures (MCS) of human colorectal cancer cells. Tumor penetration of CKD-602 could not be determined due to loss of activity after penetration through cell free insert membrane, which warrants further evaluation using a modified model.

Amyloid has been reported have an effect on the induction of oxidative stress that involves the functional and structural abnormalities in Alzheimer's disease. As a role of a radical scavenger, a green tea treatment was found have some inhibitory effect on the neurodegenerative process. The aim of this study was to determine if green tea catechin (GTC) reduces in transgenic model. To test this, transgenic mice carrying neuronspecific enolase (NSE) controlled C-terminus (105) of APP (APP-C105) were created and treated them with a low ana high dose of GTC for 6 months. Herein, we conclude that transgenic mice expressing NSE/APP-C105 were successfully created and the GTC-treated group exhibited significant reduction in body weight. Thus, GTC might be a good prevention of obesity or good treatment for AD patient.

We examined the effects of psoralen derivatives on a rapidly activating delayed rectifier channel (hKv1.5) cloned from human heart and stably expressed in cells. Using the whole cell configuration of the patch-clamp technique, we found that the five psoralen derivatives inhibited hKv1.5 current. Especially, 4-(2-Propenyloxy)-7H-furo[3,2-g][1]benzopyran-7-one (compound 5) was more potent than the inhibition of the hKv1.5 current of psoralen. The compound 5 inhibited the hKv1.5 current in a concentration-, time-, and voltage-dependent manner. These results suggest that the compound 5 is an excellent candidate as an antiarrhythmic drug for atrial fibrillation.

Neprilysin (Nep) is known to be important to degrade derived from amyloid precursor protein (APP) by cleavage with -secretases. In order to determine whether a correspondence between activity and Nep levels exists in postnatal aging of transgenic mice expressing either neuron-specific enolase (NSE)-controlled human mutant presenilin-2 (hPS2m) or APPsw alone, the levels of Nep expression and activity were examined age of 5, 12, and 20 months, respectively. The levels of Nep expression in both types of transgenic brains were decreased relative to those of control mice in a aging-related manner, while the level of activity was reversibly increased. Thus, changes in may all reflect variation in amounts of Nep enzyme.

We tested effect of sarcotride A, a bioactive cyclitol derivative from a marine sponge, on membrane potential in C6 glioma cells. Membrane potential was estimated by measuring fluorescence change of DiBAC-loaded glioma cells. Sarcotride A increased membrane potential in a concentration-dependent manner. We tested effects of pertussis toxin, U73122, EIPA, and media on sarcotride A-induced increase of membrane potential to investigate involvement of G proteins, phospholipase C, exchanger, and channels. However, we were not able to observe any significant effect of those pharmacological inhibitors, excluding the involvement of the molecules as candidate targets or signaling molecules of sarcotride A-induced increase of membrane potential. Further investigation is necessary to elucidate action mechanism of sarcotride A.

Depression is a very difficult disease to be cured because several nervous systems are involved. In the present study, we evaluated the effects of Keum-Ryung-Ja-San (KRJS), a traditional herbal prescription, on depressive behaviors in mice using the forced swimming test. KRJS was given 1 h prior to the forced swimming test (50, 100, 200, an400 mg/kg, p.o.). The duration of immobility time in the forced swimming test was significantly reduced by KRJS treatment (200 mg/kg, P<0.05) and similar effects were observed with a classical antidepressant, imipramine (15 mg/kg, i.p.). With subchronic administrations of KRJS and its constituents at several doses for 1 week, a decreased duration of immobility time was observed with KRJS and Corydalis ternata (200 mg/kg, p.o. P<0.05). These results suggest that KRJS may have antidedpressive activities and CT may contribute to the antidepressive activity of KRJS.

This study was performed to investigate the influence of the spinal adenosine receptors on the central regulation of blood pressure (BP) and heart rate (HR), and to define whether its mechanism is mediated by cyclic AMP (cAMP), cyclic GMP (cGMP) or potassium channel. Intrathecal (i.t.) administration of drugs at the thoracic level were performed in anesthetized, artificially ventilated male Sprague-Dawley rats. I.t. injection of adenosine receptor agonist, -cyclohexyladenosine (CHA; 1, 5 and 10 nmol) produced dose dependent decrease of BP and HR and it was attenuated by pretreatment of 50 nmol of 8-cyclopentyl-1,3-dimethylxanthine, a specific adenosine receptor antagonist. Pretreatment with a cAMP analogue, 8-bromo-cAMP, also attenuated the depressor and bradycardiac effects of CHA (10 nmol), but not with cGMP analogue, 8-bromo-cGMP. Pretreatment with a ATP-sensitive potassium channel blocker, glipizide (20 nmol) also attenuated the depressor and bradycardiac effects of CHA (10 nmol). These results suggest that adenosine receptor in the spinal cord plays an inhibitory role in the central cardiovascular regulation and that this depressor and bradycardiac actions are mediated by cAMP and potassium channel.