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Inhibitory effects of the atypical antipsychotic, clozapine, on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

  • Kang, Minji;Heo, Ryeon;Park, Seojin;Mun, Seo-Yeong;Park, Minju;Han, Eun-Taek;Han, Jin-Hee;Chun, Wanjoo;Ha, Kwon-Soo;Park, Hongzoo;Jung, Won-Kyo;Choi, Il-Whan;Park, Won Sun
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.4
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    • pp.277-285
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    • 2022
  • To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an half-inhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06. Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapine-induced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentration-and use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapine-induced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.

Cardioprotective Potential of Gracilaria Verrucosa Extract in Myocardial Infarction-Induced Heart Failure Model (심근 경색 유발 심부전 모델에서 강리 추출물의 심장 보호 가능성)

  • Youn Jae Jang;Hye Yoom Kim;Jung Joo Yoon;Byung Hyuk Han;Je Kuk Yu;Nam Geun Cho;Ho Sub Lee;Dae Gill Kang
    • Herbal Formula Science
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    • v.31 no.3
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    • pp.157-169
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    • 2023
  • Gracilaria Verrucosa (GV), a seaweed used in traditional Korean medicine, was studied for its effects on MI-induced heart failure in rats. MI is caused by a blocked coronary artery, leading to severe cardiac dysfunction. The study used a rat model to assess cardiac changes over time and evaluate the impact of GV on heart failure. Ischemia was induced through LAD ligation surgery, and the extent of ischemic area was measured as a prognostic factor. GV extract administration significantly improved cardiac morphology and reduced cardiac weight compared to the MI group. GV treatment also improved cardiac function, as evidenced by positive effects on chamber dilation during MI-induced heart failure. Parameters such as ejection fraction (EF) and fractional shortening (FS) were measured. The MI group showed decreased EF and FS compared to the sham group, while these parameters improved in the GV group. GV treatment also reduced levels of LDH, CPK, and CK-MB in the serum, indicating reduced myocardial damage. Histological analysis revealed that GV treatment attenuated cardiac hypertrophy and fibrosis, with reduced collagen deposition in the myocardium. Immunohistochemistry analysis showed suppressed expression of TGF-β1 and collagen 1, involved in fibrosis. In conclusion, GV showed potential in improving cardiac function in a rat model of MI-induced heart failure. It alleviated myocardial damage, attenuated cardiac hypertrophy and fibrosis, and suppressed fibrotic markers. Further studies are needed to explore its clinical efficacy and underlying mechanisms in cardiac diseases beyond animal models.

Preprocessing Technique for Malicious Comments Detection Considering the Form of Comments Used in the Online Community (온라인 커뮤니티에서 사용되는 댓글의 형태를 고려한 악플 탐지를 위한 전처리 기법)

  • Kim Hae Soo;Kim Mi Hui
    • KIPS Transactions on Computer and Communication Systems
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    • v.12 no.3
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    • pp.103-110
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    • 2023
  • With the spread of the Internet, anonymous communities emerged along with the activation of communities for communication between people, and many users are doing harm to others, such as posting aggressive posts and leaving comments using anonymity. In the past, administrators directly checked posts and comments, then deleted and blocked them, but as the number of community users increased, they reached a level that managers could not continue to monitor. Initially, word filtering techniques were used to prevent malicious writing from being posted in a form that could not post or comment if a specific word was included, but they avoided filtering in a bypassed form, such as using similar words. As a way to solve this problem, deep learning was used to monitor posts posted by users in real-time, but recently, the community uses words that can only be understood by the community or from a human perspective, not from a general Korean word. There are various types and forms of characters, making it difficult to learn everything in the artificial intelligence model. Therefore, in this paper, we proposes a preprocessing technique in which each character of a sentence is imaged using a CNN model that learns the consonants, vowel and spacing images of Korean word and converts characters that can only be understood from a human perspective into characters predicted by the CNN model. As a result of the experiment, it was confirmed that the performance of the LSTM, BiLSTM and CNN-BiLSTM models increased by 3.2%, 3.3%, and 4.88%, respectively, through the proposed preprocessing technique.

Valproic Acid-induced PPAR-alpha and FGF21 Expression Involves Survival Response in Hepatocytes (Valproic acid에 의해 증가하는 PPAR-alpha 및 FGF21의 발현이 간세포 생존에 미치는 영향)

  • Bakhovuddin Azamov;Yeowon Kang;Chanhee Lee;Wan-Seog Shim;Kwang Min Lee;Parkyong Song
    • Journal of Life Science
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    • v.34 no.4
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    • pp.227-235
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    • 2024
  • Hepatocyte damage caused by medications or herbal products is one of the important problem when these compounds are chronically administrated. Thus, improving hepatocyte survival during treatment offers a wide range of opportunities. Valproic acid (VPA), a branched short-chain fatty acid derived from naturally occurring valeric acid, is commonly used to treat epilepsy and seizures. Although VPA exerts numerous effects in cancer, HIV therapy, and neurodegenerative disease, its effects on the liver and its mechanism of action have not been fully elucidated. Here, we demonstrated that VPA caused moderate liver cell toxicity and apoptosis. Interestingly, VPA treatment increased transcription levels of PPAR alpha (PPAR-α) and fibroblast growth factor 21 (FGF21) in murine (Hepa1c1c7) hepatoma cells in a time and concentration dependent manner. VPA-induced FGF21 expression was significantly weaker under PPAR-α silencing condition than in cells transfected with non-targeting control siRNA. Subsequent experiments showed that cell viability was significantly lowered when the FGF21 signaling pathway was blocked by FGF receptor antagonist. Finally, we further determined that AMPK phosphorylation was not responsible for VPA-induced FGF21 expression and PPAR-a increments. These results indicate that increases of FGF21 expression alleviate VPA-induced hepatic toxicity, thereby making FGF21 a potential biomarker for predicting liver damage during VPA treatments.

A Case Study on Implementation of Mobile Information Security (모바일 정보보안을 위한 실시간 모바일 기기 제어 및 관리 시스템 설계.구현 사례연구)

  • Kang, Yong-Sik;Kwon, Sun-Dong;Lee, Kang-Hyun
    • Information Systems Review
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    • v.15 no.2
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    • pp.1-19
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    • 2013
  • Smart working sparked by iPhone3 opens a revolution in smart ways of working at any time, regardless of location and environment. Also, It provide real-time information processing and analysis, rapid decision-making and the productivity of businesses, including through the timely response and the opportunity to increase the efficiency. As a result, every company are developing mobile information systems. But company data is accessed from the outside, it has problems to solve like security, hacking and information leakage. Also, Mobile devices such as smart phones belonging to the privately-owned asset can't be always controlled to archive company security policy. In the meantime, public smart phones owned by company was always applied security policy. But it can't not apply to privately-owned smart phones. Thus, this paper is focused to archive company security policy, but also enable the individual's free to use of smart phones when we use mobile information systems. So, when we use smart phone as individual purpose, the normal operation of all smart phone functions. But, when we use smart phone as company purpose like mobile information systems, the smart phone functions are blocked like screen capture, Wi-Fi, camera to protect company data. In this study, we suggest the design and implementation of real time control and management of mobile device using MDM(Mobile Device Management) solution. As a result, we can archive company security policy and individual using of smart phone and it is the optimal solution in the BYOD(Bring Your Own Device) era.

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The Role of Interleukin 8 and NF(nuclear factor)-κB in Rhinovirus-Induced Airway Inflammation (Rhinovirus 유발성 기도염증반응에서 Interleukin-8과 전사인자 NF(nuclear factor)-κB의 역할에 대한 연구)

  • Yoon, Ho Joo;Kim, Mi Ok;Sohn, Jang Won;Kim, Jung Mogg;Shin, Dong Ho;Park, Sung Soo
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.1
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    • pp.104-113
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    • 2003
  • Background : Rhinovirus(RV) infections frequently trigger dyspnea and paroxysmal cough in adult patients with asthma and are the most prevalent cause of the common cold. However, the mechanisms of a RV-induced airway inflammation is unclear. Since the RV does not directly destroy the airway epithelium, it is presumed that the immune response to the RV contributes to the pathogenesis of the respiratory symptoms. In order to test this hypothesis, this study characterized the time-sequenced alterations in interleukin(IL)-8 elaboration from the human bronchial epithelial cells and evaluated the role of NF(nuclear factor)-${\kappa}B$ in the RV-induced IL-8 production by pretreating the inhibitors of NF-${\kappa}B$ activation. Methods : The ability of RV-infected human bronchial epithelial cells and BEAS-2B cells to produce the IL-8 was compared with the controls. This study infected BEAS-2B cells with the RV14 obtained from the American Type Culture Collection. The supernatants were harvested from the RV infected BEAS-2B cells and the controls at 2hr, 4hr, 6hr, 12hr, 24hr, 48hr from the inoculation time. This study measured the IL-8 concentration using the ELISA kits. In order to elucidate the role of NF-${\kappa}B$ in the RV-induced IL-8 production, the effect of the NF-${\kappa}B$ inhibitors was evaluated on RV-induced IL-8 production. Results: The BEAS-2B cells produced small amounts of IL-8 that accumulated slowly with time in the culture. The RV was a potent stimulator of the IL-8 proteins production by BEAS-2B human bronchial epithelial cells. Antioxidants, N-acetyl-L-cysteine(NAC),\ and pyrrolidine dithiocarbamate(PDTC), blocked the IL-8 elaboration by the RV-infected BEAS-2B cells, which was dose-dependent, but N-Tosyl-L-phenylalanine chloromethyl ketone(TPCK) did not. Conclusion: Some antioxidants inhibited the RV-induced IL-8 production by blocking the NF-${\kappa}B$, which may have a therapeutic potential in asthma.

Effect of Auriculotemporal Nerve Block Anesthesia on Manual Reduction of Disc Displacement without Reduction of the Temporomandibular Joint (악관절의 비정복성관절원판변위의 수조작 정복에 대한 이개측두신경 전달마취의 효과)

  • Kim, Sook-Young;Kim, Ji-Yeon;Hong, Su-Min;Kim, Byung-Gook;Park, Byung-Ju;Im, Yeong-Gwan
    • Journal of Oral Medicine and Pain
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    • v.36 no.1
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    • pp.71-79
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    • 2011
  • Aim: Disc displacement without reduction of the temporomandibular joint (TMJ) has been managed by mandibular manipulation to reduce the displaced disc but with a low success rate. The purpose of this study was to determine whether auriculotemporal nerve block anesthesia had an effect on the reduction of the displaced disc and to analyze the factors that influenced the result. Methods: 112 patients were diagnosed with disc displacement without reduction and treated by mandibular manipulation. Disc was recaptured in 35 patients. Among the 77 patients with whom disc recapture had failed, the auriculotemporal nerve was blocked with a local anesthetic in the 49 patients (mean $age \;{\pm}\; SD\; =\; 34.4\;{\pm}\; 15.1$; male 24, female 25) and then mandibular manipulation was performed again. Factors including age, elapsed time from the onset, and opening amount were analyzed in association with disc reduction rate with the auriculotemporal nerve block. Results: Among 49 patients who did not respond to manipulation only, manual reduction with auriculotemporal nerve block anesthesia was successful in 19 patients (38.8%). Maximum unassisted opening amount significantly increased in the 19 patients with successful recapture of the disc ($mean \;{\pm}\; SD\; =\; 46.1 \;{\pm}\; 4.5\; mm$), in contrast to the limited opening amount of the 49 patients before local anesthesia of the auriculotemporal nerve ($mean \;{\pm}\; SD\; =\; 25.7 \;{\pm}\; 6.0\; mm$). Age, elapsed time after the onset, and preoperative opening amount were not associated with the reduction rate. Conclusion: The results of this study suggest that auriculotemporal nerve block anesthesia increases the reduction rate of the disc displacement without reduction of the TMJ when combined with mandibular manipulation, and such anesthesia should be applied at the first stage of manual treatment of disc displacement without reduction.

The Comparison of the Solar Radiation and the Mean Radiant Temperature (MRT) under the Shade of Landscaping Trees in Summertime (하절기 조경용 녹음수 수관 하부의 일사와 평균복사온도 비교)

  • Lee, Chun-Seok;Ryu, Nam-Hyung
    • Journal of the Korean Institute of Landscape Architecture
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    • v.42 no.5
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    • pp.22-30
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    • 2014
  • The purpose of this study was to compare the Solar Radiation(SR) and the Mean Radiant Temperature(MRT) under the shades of the three landscaping trees in clear summer daytimes. The trees were Lagerstroemia indica, Quercus palustris and Ulmus parvifolia. The solar radiation, the globe temperature and the air temperature were recorded every minute from the $1^{st}$ of April to the $30^{th}$ of September 2013 at a height of 1.1m above on the four monitoring stations, with four same measuring system consisting of a solar radiation sensor, two resistance temperature detectors(Pt-100), a black brass globe (${\phi}50mm$) and data acquisition systems. At the same time, the sky view photos were taken automatically hourly by three scouting cameras(lens angle: $60^{\circ}$) fixed at each monitoring station. Based on the 258 daily sky view photos and 6,640 records of middays(10 A.M.~2 P.M.) from the $1^{st}$ of June to the $30^{th}$ of August, the time serial differences of SR and MRT under the trees were analysed and compared with those of open sky, The major findings were as follows; 1. The average ratio of sky views screened by the canopies of Quercus palustris, Lagerstroemia indica and Ulmus parvifolia were 99%, 98% and 97%, and the SR were $106W/m^2$, $163W/m^2$ and $202W/m^2$ respectively, while the SR of open sky was $823W/m^2$. Which shows the canopies blocked at least 70% of natural SR. 2. The average MRT under the canopies of Quercus palustris, Lagerstroemia indica and Ulmus parvifolia were $30.34^{\circ}C$, $33.34^{\circ}C$ and $34.77^{\circ}C$ respectively, while that of open sky was $46.0^{\circ}C$. Therefore, it can be said that the tree canopies can reduce the MRT around $10{\sim}16^{\circ}C$. 3. The regression test showed significant linear relationship between the SR and MRT. In summary, the performances of the landscaping shade trees were very good at screening the SR and reducing the MRT at the outdoor of summer middays. Therefore, it can be apparently said that the more shade trees or forest at the outdoor, the more effective in conditioning the outdoor space reducing the MRT and the useless SR for human activities in summertime.

Characterization of Repeated Deactivation and Subsequent Re-activation of Photocatalyst Used in Two Alternatively-operating UV/photocatalytic Reactors of Waste-air Treating System (교대로 운전되는 두 개의 UV/광촉매반응기로 구성된 폐가스 처리시스템에서의 광촉매의 비활성화 및 재생 특성)

  • Lee, Eun Ju;Chung, Chan Hong;Lim, Kwang-Hee
    • Korean Chemical Engineering Research
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    • v.59 no.4
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    • pp.584-595
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    • 2021
  • In this study, the correlation between operating stages of waste air-treating system composed of two alternatively-operating UV/photocatalytic reactors, and the deactivation of photocatalyst used in each operating stage, was investigated by instrumental analysis thereon. The repeated deactivation and subsequent re-generation of photocatalyst used in the waste air treating system of previous investigation performed by Lee and Lim (Korean Chem. Eng. Research, 59(4), 574-583(2021)), were characterized on virgin photocatalyst-carrying porous SiO2 media (A4), used photocatalyst-carrying porous SiO2 media (A1, A2 and A3) collected from the corresponding photocatalytic reactor upon 1st, 2nd, and 3rd run, respectively, regenerated photocatalyst-carrying porous SiO2 media upon 1 time-run (AD1) and 3 times regenerated photocatalyst-carrying porous SiO2 media upon 3 time-runs (AD3) by instrumental analysis including BET analysis, SEM, XPS, SEM-EDS and FT-IR. As a result, the proper regeneration-temperature for deactivated photocatalyst to be regenerated several times (more than 3 times), was suggested below 200 ℃. Such temperature of deactivated photocatalyst-regeneration was almost consistent to the one, according to BET analysis, at which tiny nano-pores blocked by adsorbed ethanol-oxidative and degraded intermediates (AEODI), were regenerated to be reopened through almost complete mineralization of AEODI. In particular, the results of XPS analysis indicated an incurrence of insignificant deactivation of photocatalysis upon 1st run of UV/photocatalytic reactor (A or C) of the previous investigation. In addition, the results of XPS analysis were consistent with the experimental results of the previous investigation in that 1) deactivation of photocatalyst incurred during 2nd run of the UV/photocatalytic reactor (A or C) resulted in decreased removal efficiency, by ca. 5% and 5%, of ethanol and hydrogen sulfide, respectively, compared with its 1st run; 2) there was insignificant difference between the removal efficiencies of its 2nd run and 3rd run. Furthermore, the removal efficiencies of ethanol and hydrogen sulfide for hypothetical 4th run of photocatalytic reactor in the previous investigation, using AD3, were expected to decrease, compared with its 3rd run, by much more than those for 2nd run in the previous investigation did, compared with its 1st run.

Lysophosphatidic Acid Stimulates SKOV-3 Cell Migration through the Generation of Reactive Oxygen Species via the mTORC2/Akt1/NOX Signaling Axis (리소포스타티드산은 SKOV-3 난소암세포의 mTORC2/Akt1/NOX 신호전달 기전을 통해 활성산소를 형성하고 이를 통해 세포의 이동을 촉진)

  • Eun Kyoung Kim;Seo Yeon Jin;Jung Min Ha;Sun Sik Bae
    • Journal of Life Science
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    • v.33 no.2
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    • pp.129-137
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    • 2023
  • Reactive oxygen species (ROS) play an essential role in a variety of cellular physiological phenomena. The present study assessed the signaling axis that mediates the lysophosphatidic acid (LPA)-induced migration of SKOV-3 cells. Insulin-like growth factor-1 (IGF-1) stimulated SKOV-3 cell migration in a time- and dose-dependent manner. Similarly, LPA stimulated SKOV-3 cell migration and the phosphorylation of Akt in a time- and dose-dependent manner. The pharmacological inhibition of LPA receptors (LPA1/LPA3) significantly suppressed LPA-induced SKOV-3 cell migration. However, IGF-1-induced SKOV-3 cell migration was not affected by the inhibition of LPA1 and LPA3. Pharmacological inhibition of phosphoinositide 3-kinase (PI3K) or Rho-associated kinase (ROCK) significantly suppressed LPA-induced migration, whereas the inhibition of MAPK kinase (MEK) had no effect. Inhibition of PI3K or ROCK completely suppressed LPA-induced ROS generation, and suppression of nicotinamide adenine dinucleotide phosphate oxidase (NOX) or chelation of ROS by N-acetylcysteine (NAC) blocked LPA-induced SKOV-3 cell migration. LPA-induced ROS generation was suppressed by silencing Rictor or Akt1 but not Raptor or Akt2. Silencing Rictor or Akt1 significantly suppressed LPA-induced SKOV-3 cell migration, whereas silencing Raptor or Akt2 had no effect. Finally, the overexpression of the constitutively active form Akt1 (CA-Akt1) significantly enhanced the LPA-induced migration of SKOV-3 cells. Given these results, we suggest that LPA stimulates SKOV-3 cell migration by ROS generation, which is mediated by the mTORC2/Akt1/NOX signaling axis.