Effects of ethanol exposure during early pregnancy in hyperactive, inattentive and impulsive behaviors and MeCP2 expression in rodent offspring.

Kim, Pitna,Park, Jin Hee,Choi, Chang Soon,Choi, Inah,Joo, So Hyun,Kim, Min Kyoung,Kim, Soo Young,Kim, Ki Chan,Park, Seung Hwa,Kwon, Kyoung Ja,Lee, Jongmin,Han, Seol-Heui,Ryu, Jong Hoon,Cheong, Jae Hoo Kluwer Academic/Plenum Publishers 2013 Neurochem Res Vol.38 No.3

<P>Prenatal exposure to alcohol has consistently been associated with adverse effects on neurodevelopment, which is collectively called fetal alcohol spectrum disorder (FASD). Increasing evidence suggest that prenatal exposure to alcohol increases the risk of developing attention deficit/hyperactivity disorder-like behavior in human. In this study, we investigated the behavioral effects of prenatal exposure to EtOH in offspring mice and rats focusing on hyperactivity and impulsivity. We also examined changes in dopamine transporter and MeCP2 expression, which may underlie as a key neurobiological and epigenetic determinant in FASD and hyperactive, inattentive and impulsive behaviors. Mouse or rat offspring born from dam exposed to alcohol during pregnancy (EtOH group) showed hyper locomotive activity, attention deficit and impulsivity. EtOH group also showed increased dopamine transporter and norepinephrine transporter level compared to control group in the prefrontal cortex and striatum. Prenatal exposure to EtOH also significantly decreased the expression of MeCP2 in both prefrontal cortex and striatum. These results suggest that prenatal exposure to EtOH induces hyperactive, inattentive and impulsive behaviors in rodent offspring that might be related to global epigenetic changes as well as aberration in catecholamine neurotransmitter transporter system.</P>

Rehmannia glutinosa suppresses inflammatory responses elicited by advanced glycation end products.

Baek, Gui-Hyun,Jang, Yong-Suk,Jeong, Seung-Il,Cha, Jaeho,Joo, Myungsoo,Shin, Sang-Woo,Ha, Ki-Tae,Jeong, Han-Sol Kluwer Academic/Plenum Publishers 2012 INFLAMMATION Vol.35 No.4

<P>Fresh rhizome of Rehmannia glutinosa Libosch. (Saeng-jihwang in Korean: SJH) has been prescribed for the treatment of diabetes-associated complications. The purpose of the present study is to investigate the underlying mechanisms of the efficacy of SJH in diabetes-related complications. Decoction was obtained after boiling SJH in water and subsequent lyophilization. The cellular toxicity of SJH was determined by MTT assay. The antioxidant activity of SJH was measured by DPPH and DCFH-DA assays. The effects of SJH on inflammatory responses elicited by AGEs were assessed by western blotting and semi-quantitative RT-PCR analyses. The water extract of SJH had a high free radical scavenging activity in vitro and decreased the level of intracellular ROS in THP-1 cells treated with AGEs. SJH suppressed the expression of pro-inflammatory genes, including TNF-α, MCP-1, IP-10, COX-2, and iNOS; the activation of NF-κB; and the expression of RAGE, a receptor for AGEs, where the expressions of which were induced by AGEs. These results suggest the possibility that SJH can be an alternative therapeutics for diabetes-associated diseases.</P>

An acoustical evaluation of knee sound for non-invasive screening and early detection of articular pathology.

Kim, Keo Sik,Seo, Jeong Hwan,Song, Chul Gyu Kluwer Academic/Plenum Publishers 2012 JOURNAL OF MEDICAL SYSTEMS Vol.36 No.2

<P>Knee sound signals generated by knee movement are sometimes associated with degeneration of the knee joint surface and such sounds may be a useful index for early disease. In this study, we detected the acoustical parameters, such as the fundamental frequency (F0), mean amplitude of the pitches, and jitter and shimmer of knee sounds, and compared them according to the pathological conditions. Six normal subjects (4 males and 2 females, age: 28.3??2.3 years) and 11 patients with knee problems were enrolled. The patients were divided into the 1st patient group (5 males and 1 female, age: 30.2??10.3 years) with ruptured wounds of the meniscus and 2nd patient group (2 males and 3 females, age: 42.1??16.2 years) with osteoarthritis. The mean values of F0, jitter and shimmer of the 2nd patient group were larger than those of the normal group, whereas those of the 1st patient group were smaller (p?<?0.05). Also, the F0 and jitter in the standing position were larger than those in the sitting position in both the 1st and 2nd patient groups (p?<?0.05). These results showed good potential for the non-invasive diagnosis and early detection of articular pathologies via an auscultation.</P>

Antiseptic Effects of New 3'-N-Substituted Carbazole Derivatives In Vitro and In Vivo.

Lee, Wonhwa,Kwak, Soyoung,Yun, Eunju,Lee, Jee Hyun,Na, MinKyun,Song, Gyu-Yong,Bae, Jong-Sup Kluwer Academic/Plenum Publishers 2015 INFLAMMATION Vol.38 No.4

<P>Inhibition of high-mobility group box 1 (HMGB1) protein and restoration of endothelial integrity are emerging as attractive therapeutic strategies in the management of sepsis. Here, new five structurally related 3'-N-substituted carbazole derivatives were examined for their effects on lipopolysaccharide (LPS)-mediated or cecal ligation and puncture (CLP)-mediated release of HMGB1 and on modulation of HMGB1-mediated inflammatory responses. We accessed this question by monitoring the effects of posttreatment carbazole derivatives on LPS- and CLP-mediated release of HMGB1 and HMGB1-mediated regulation of proinflammatory responses in human umbilical vein endothelial cells (HUVECs) and septic mice. The new 3'-N-substituted carbazole derivatives 1-5 inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. New compounds also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with each compound reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in mice. These results indicate that the new 3'-N-substituted carbazole derivatives could be candidate therapeutic agents for various severe vascular inflammatory diseases owing to their inhibition of the HMGB1 signaling pathway.</P>

Neuroprotective effects of PEP-1-Cu,Zn-SOD against ischemic neuronal damage in the rabbit spinal cord.

Kim, Woosuk,Kim, Dae Won,Yoo, Dae Young,Chung, Jin Young,Hwang, In Koo,Won, Moo-Ho,Choi, Soo Young,Jeon, Sei Woong,Jeong, Je Hoon,Hwang, Hyung Sik,Moon, Seung Myung Kluwer Academic/Plenum Publishers 2012 Neurochem Res Vol.37 No.2

<P>A rabbit model of spinal cord ischemia has been introduced as a good model to investigate the pathophysiology of ischemia-reperfusion (I-R)-induced paraplegia. In the present study, we observed the effects of Cu,Zn-superoxide dismutase (SOD1) against ischemic damage in the ventral horn of L(5-6) levels in the rabbit spinal cord. For this study, the expression vector PEP-1 was constructed, and this vector was fused with SOD1 to create a PEP-1-SOD1 fusion protein that easily penetrated the blood-brain barrier. Spinal cord ischemia was induced by transient occlusion of the abdominal aorta for 15 min. PEP-1-SOD1 (0.5 mg/kg) was intraperitoneally administered to rabbits 30 min before ischemic surgery. The administration of PEP-1-SOD1 significantly improved neurological scores compared to those in the PEP-1 (vehicle)-treated ischemia group. Also, in this group, the number of cresyl violet-positive cells at 72 h after I-R was much higher than that in the vehicle-treated ischemia group. Malondialdehyde levels were significantly decreased in the ischemic spinal cord of the PEP-1-SOD1-treated ischemia group compared to those in the vehicle-treated ischemia group. In contrast, the administration of PEP-1-SOD1 significantly ameliorated the ischemia-induced reduction of SOD and catalase levels in the ischemic spinal cord. These results suggest that PEP-1-SOD1 protects neurons from spinal ischemic damage by decreasing lipid peroxidation and maintaining SOD and catalase levels in the ischemic rabbit spinal cord.</P>

A novel synthetic compound 4-acetyl-3-methyl-6-(2-bromophenyl)pyrano[3,4-c]pyran-1,8-dione inhibits the production of nitric oxide and proinflammatory cytokines via the NF-κB pathway in lipopolysaccharide-activated microglia cells.

Chung, Hwan-Suck,Kim, Sae-Noon,Jeong, Jin-Hyun,Bae, Hyunsu Kluwer Academic/Plenum Publishers 2013 Neurochem Res Vol.38 No.4

<P>Previously, we discovered a new compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione (PPY), from Vitex rotundifolia L. and evaluated its anti-inflammatory and anti-asthmatic effects. In this study, we synthesized a new, modified compound 4-acetyl-3-methyl-6-(2-bromophenyl)pyrano[3,4-c]pyran-1,8-dione (PPY-Br) based on the PPY skeleton and evaluated its anti-inflammatory effects in lipopolysaccharide (LPS)-activated microglia. PPY-Br suppresses nitric oxide production, inducible nitric oxide synthase expression, and tumor necrosis factor-α and interleukin-6 production in LPS-activated BV-2 microglial cell line and mouse primary microglia. The effect of PPY-Br on the activation of nuclear factor (NF)-kappaB was examined to identify the mechanism involved. The LPS-induced translocation of NF-κB to the nucleus and phosphorylation of inhibitory-kappaB were almost completely blocked by PPY-Br. This study indicates that PPY-Br significantly attenuates the level of neurotoxic, proinflammatory mediators and proinflammatory cytokines via inhibition of the NF-κB signaling pathway. We suggest that PPY-Br presents a new candidate treatment for various neuro-inflammatory diseases.</P>

The adenosine A3 receptor agonist Cl-IB-MECA induces cell death through Ca2?/ROS-dependent down regulation of ERK and Akt in A172 human glioma cells.

Kim, Thae Hyun,Kim, Yong Keun,Woo, Jae Suk Kluwer Academic/Plenum Publishers 2012 Neurochem Res Vol.37 No.12

<P>Adenosine A(3) receptor (A3AR) is coupled to G proteins that are involved in a variety of intracellular signaling pathways and physiological functions. 2-Chloro-N(6)-(3-iodobenzyl) adenosine-5'-N-methylcarboxamide (Cl-IB-MECA), an agonist of A3AR, has been reported to induce cell death in various cancer cells. However, the effect of CI-IB-MECA on glioma cell growth is not clear. This study was undertaken to examine the effect of CI-IB-MECA on glioma cell viability and to determine its molecular mechanism. CI-IB-MECA inhibited cell proliferation and induced cell death in a dose- and time-dependent manner. Treatment of CI-IB-MECA resulted in an increase in intracellular Ca(2+) followed by enhanced reactive oxygen species (ROS) generation. EGTA and N-acetylcysteine (NAC) blocked the cell death induced by CI-IB-MECA, suggesting that Ca(2+) and ROS are involved in the Cl-IB-MECA-induced cell death. Western blot analysis showed that CI-IB-MECA induced the down-regulation of extracellular signal-regulated kinases (ERK) and Akt, which was prevented by EGTA, NAC, and the A3AR antagonist MRS1191. Transfection of constitutively active forms of MEK, the upstream kinase of ERK, and Akt prevented the cell death. CI-IB-MECA induced caspase-3 activation and the CI-IB-MECA-induced cell death was blocked by the caspase inhibitors DEVD-CHO and z-VAD-FMK. In addition, expression of XIAP and Survivin were decreased in cells treated with Cl-IB-MECA. Collectively, these findings demonstrate that CI-IB-MECA induce a caspase-dependent cell death through suppression of ERK and Akt mediated by an increase in intracellular Ca(2+) and ROS generation in human glioma cells. These suggest that A3AR agonists may be a potential therapeutic agent for induction of apoptosis in human glioma cells.</P>

Dichloromethane fraction of Laminaria japonica ethanolic extract inhibits lipopolysaccharide-induced nitric oxide synthase and cyclooxygenase-2 expression in RAW 264.7 cells via NF-κB pathway.

Lee, Ji-Young,Lee, Min-Sup,Choi, Ji-Woong,Shin, Tai Sun,Woo, Hee-Chul,Kim, Hyeung-Rak Kluwer Academic/Plenum Publishers 2012 INFLAMMATION Vol.35 No.5

<P>Strong anti-inflammatory activity has been found in Laminaria japonica dichloromethane fraction (LDF); however, the molecular mechanisms underlying its anti-inflammatory activity are not reported. Our results indicated that LDF inhibited LPS-induced nitric oxide and prostaglandin E(2) production in a dose-dependent manner and suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in RAW 264.7 cells. Also, levels of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β and IL-6 were remarkably reduced by LDF in LPS-treated RAW 264.7 cells. LDF greatly inhibited promoter activity of nuclear factor-κB (NF-κB) and translocation of NF-κB subunits by prevention of the degradation of inhibitor κB-α in LPS-treated RAW 264.7 cells (p?<?0.05). Moreover, LDF inhibited activation of mitogen-activated protein kinases and AKT in LPS-treated RAW 264.7 cells. These results indicate that the LDF downregulates iNOS and COX-2 expressions through the suppression of NF-κB pathway associated with inhibition of multiple signaling proteins.</P>

Reduced beta-catenin expression in the hippocampal CA1 region following transient cerebral ischemia in the gerbil.

Cho, Jeong-Hwi,Yan, Bing Chun,Lee, Young Joo,Park, Joon Ha,Ahn, Ji Hyeon,Kim, In Hye,Lee, Jae-Chul,Kim, Young-Myeong,Lee, Bonghee,Cho, Jun Hwi,Won, Moo-Ho Kluwer Academic/Plenum Publishers 2013 Neurochem Res Vol.38 No.5

<P>Beta-catenin, a transcription factor, plays a critical role in cell survival and degradation after stroke. In this study, we examined changes of expression in beta-catenin in the hippocampal CA1 region of the gerbil following 5 min of transient cerebral ischemia. We observed neuronal damage using cresyl violet staining, neuronal nuclei immunohistochemistry and Fluro-Jade B immunofluorescence. Four days after ischemia-reperfusion (I-R), most of pyramidal cells in the CA1 region were damaged. In addition, early damage in dendrites was detected 1 day after I-R by immunohistochemical staining for microtubule-associated protein 2 (MAP-2), and MAP-2 immunoreactivity was hardly detected in the CA1 region 4 days after I-R. We found that beta-catenin (a synapse-enriched cell adhesion molecule) was well expressed in dendrites before I-R. Its immunoreactivity was well colocalized with MAP-2. Chronological change of beta-catenin immunoreactivity was novelty in the present study. Twelve hours after I-R, its immunoreactivity was decreased in the stratum radiatum of the CA1 region, however, its immunoreactivity was increased 1 and 2 days after I-R, and decreased sharply 4 days after I-R. However, we did not find any change in beta-catenin immunoreactivity in the CA2 and CA3 region. In brief, we suggest that early change of beta-catenin expression in the stratum pyramidale of ischemic hippocampal CA1 region is associated with early dendrite damage following transient cerebral ischemia.</P>

Protective effects of a novel synthetic α-lipoic acid-decursinol hybrid compound in experimentally induced transient cerebral ischemia.

Lee, Tae Hun,Park, Joon Ha,Kim, Jong-Dai,Lee, Jae-Chul,Kim, In Hye,Yim, Yongbae,Lee, Seul Ki,Yan, Bing Chun,Ahn, Ji Hyeon,Lee, Choong Hyun,Yoo, Ki-Yeon,Choi, Jung Hoon,Hwang, In Koo,Park, Jeong Ho,Won Kluwer Academic/Plenum Publishers 2012 Cellular and molecular neurobiology Vol.32 No.7

<P>Alpha-lipoic acid (ALA), a natural antioxidant, is widely used for the treatment of some diseases including diabetes, and decursinol (DA), a constituent of root of Angelica gigas Nakai, has some pharmacological activities including anti-inflammatory function. In this study, we synthesized a novel synthetic alpha-lipoic acid-decursinol (ALA-DA) hybrid compound, and compared neuroprotective effects of ALA, DA or ALA-DA against ischemic damage in the gerbil hippocampal CA1 region induced by 5 min of transient cerebral ischemia. In the 10 and 20 mg/kg ALA-, DA- and 10 mg/kg ALA-DA-pre-treated-ischemia-groups, there were no neuroprotective effects against ischemic damage 4 days after ischemic injury. However, 20 mg/kg ALA-DA pre-treatment protected pyramidal neurons from ischemic damage in the CA1 region. In addition, 20 mg/kg ALA-DA pre-treatment markedly decreased the activation of astrocytes and microglia in the CA1 region 4 days after ischemic injury. On the other hand, post-treatment with the same dosages of them did not show any neuroprotective effect against ischemic damage. In brief, these findings indicate that pre-treatment with ALA-DA, not ALA or DA alone, can protect neurons from ischemic damage in the hippocampus induced by transient cerebral ischemia via the decrease of glial activation.</P>