• Title/Summary/Keyword: Selective Mechanism

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Antihyperalgesic Effects of Ethosuximide and Mibefradil, T-type Voltage Activated Calcium Channel Blockers, in a Rat Model of Postoperative Pain (흰쥐의 술 후 통증 모델에서 T형 칼슘 통로 차단제인 Ethosuximide와 Mibefradil의 항통각과민 효과)

  • Shinn, Helen Ki;Cha, Young Deog;Han, Jeong Uk;Yoon, Jeong Won;Kim, Boo Seong;Song, Jang Ho
    • The Korean Journal of Pain
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    • v.20 no.2
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    • pp.92-99
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    • 2007
  • Background: A correlation between a T-type voltage activated calcium channel (VACC) and pain mechanism has not yet been established. The purpose of this study is to find out the effect of ethosuximide and mibefradil, representative selective T-type VACC blockers on postoperative pain using an incisional pain model of rats. Methods: After performing a plantar incision, rats were stabilized on plastic mesh for 2 hours. Then, the rats were injected with ethosuximide or mibefradil, intraperitoneally and intrathecally. The level of withdrawal threshold to the von Frey filament near the incision site was determined and the dose response curves were obtained. Results: After an intraperitoneal ethosuximide or mibefradil injection, the dose-response curve showed a dose-dependent increase of the threshold in a withdrawal reaction. After an intrathecal injection of ethosuximide, the threshold of a withdrawal reaction to mechanical stimulation increased and the increase was dose-dependent. After an intrathecal injection of mibefradil, no change occurred in either the threshold of a withdrawal reaction to mechanical stimulation or a dose-response curve. Conclusions: The T-type VACC blockers in a rat model of postoperative pain showed the antihyperalgesic effect. This effect might be due to blockade of T-type VACC, which was distributed in the peripheral nociceptors or at the supraspinal level. Further studies of the effect of T-type VACC on a pain transmission mechanism at the spinal cord level would be needed.

Src Family Kinase Inhibitor PP2 Induces LC3 Conversion in a Manner That is Uncoupled from Autophagy and Increases Apoptosis in Multidrug-Resistant Cells

  • Kim, Yun-Ki;Ahn, Jun-Ho;Lee, Mi-Chael
    • Biomolecules & Therapeutics
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    • v.20 no.4
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    • pp.393-398
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    • 2012
  • Recently, we reported that defective autophagy may contribute to the inhibition of the growth in response to PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), a selective SFK inhibitor, in multidrug-resistant v-Ha-ras-transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr). In this study, we demonstrated that PP2 induces LC3 conversion via a mechanism that is uncoupled from autophagy and increases apoptosis in Ras-NIH 3T3/Mdr cells. PP2 preferentially induced autophagy in Ras-NIH 3T3 cells rather than in Ras-NIH 3T3/Mdr cells as determined by LC3-I to LC3-II conversion and GFP-LC3 fluorescence microscopy. Beclin 1 knockdown experiments showed that, regardless of drug resistance, PP2 induces autophagy via a Beclin 1-dependent mechanism. PP2 induced a conformational change in Beclin 1, resulting in the enhancement of the pro-autophagic activity of Beclin 1, in Ras-NIH 3T3 cells. Further, PI3K inhibition induced by wortmannin caused a significant increase in apoptosis in Ras-NIH 3T3 cells, as demonstrated by flow cytometric analysis of Annexin V staining, implying that autophagy inhibition through PI3K increases apoptosis in response to PP2 in Ras-NIH 3T3 cells. However, despite the fact that wortmannin abrogates PP2-induced GFP-LC3 punctae formation, some LC3 conversion remains in Ras-NIH 3T3/Mdr cells, suggesting that LC3 conversion may occur in an autophagy-independent manner. Taken together, these results suggest that PP2 induces LC3 conversion independent of PI3K, concomitant with the uncoupling of LC3 conversion from autophagy, in multidrug-resistant cells.

Decoding the intestinal microbiota repertoire of sow and weaned pigs using culturomic and metagenomic approaches

  • Mun, Daye;Kim, Hayoung;Shin, Minhye;Ryu, Sangdon;Song, Minho;Oh, Sangnam;Kim, Younghoon
    • Journal of Animal Science and Technology
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    • v.63 no.6
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    • pp.1423-1432
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    • 2021
  • To elucidate the role and mechanism of microbes, we combined culture-dependent and culture-independent approaches to investigate differences in gut bacterial composition between sows and weaned pigs. Under anaerobic conditions, several nonselective and selective media were used for isolation from fecal samples. All isolated bacteria were identified and classified through 16S rRNA sequencing, and the microbiota composition of the fecal samples was analyzed by metagenomics using next generation sequencing (NGS) technology. A total of 278 and 149 colonies were acquired from the sow and weaned pig fecal samples, respectively. Culturomics analysis revealed that diverse bacterial genus and species belonged to Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes were isolated from sow and weaned pigs. When comparing culture-dependent and culture-independent analyses, 191 bacterial species and 2 archaeal bacterial species were detected through culture-independent analysis, and a total of 23 bacteria were isolated through a culture-dependent approach, of which 65% were not detected by metagenomics. In conclusion, culturomics and metagenomics should be properly combined to fully understand the intestinal microbiota, and livestock-derived microbial resources should be informed by culturomic approaches to understand and utilize the mechanism of host-microbe interactions.

Design of Planetary Gear Drive Unit for Drive Conversion of Transfer case (Transfer case의 구동변환을 위한 유성기어장치 구동부 설계)

  • Youm, Kwang-Wook
    • Journal of the Korean Institute of Gas
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    • v.26 no.2
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    • pp.21-26
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    • 2022
  • Since the four-wheel drive transmits the driving force to all four wheels, the traction with the road surface increases, thereby increasing the driving force. However, it has the disadvantage of lowering fuel efficiency. Therefore, four-wheel drive is commonly used as a method of converting to optional four-wheel drive when necessary while driving in two-wheel drive. This selective four-wheel drive converts the driving force by mechanically changing the electric signal sent by the driver in the transfer case. In this study, in order to mechanically change the electrical signal, a reducer is applied to the motor to increase the torque to perform the function. Therefore, in this study, a reduction mechanism applicable to the motor inside the transfer case applied to convert the drive is derived, and the reduction ratio applying the planetary gear type is optimized accordingly. And based on the derived reduction ratio, two sets of planetary gears using a ring gear in common were applied to develop a planetary gear tooth type in which the input shaft and output shaft are decelerated in the same phase. Optimization design was carried out.

Mechanism of Human Endogenous Retrovirus (HERV) in Inflammatory Response (인간 내생 레트로바이러스(Human Endogenous Retrovirus, HERV)의 염증반응 조절 기작)

  • Ko, Eun-Ji;Cha, Hee-Jae
    • Journal of Life Science
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    • v.31 no.8
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    • pp.771-777
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    • 2021
  • Human endogenous retroviruses (HERVs) were inserted into the human genome millions of years ago but they are currently inactive and non-infectious due to recombinations, deletions, and mutations after insertion into the host genome. Nonetheless, recent studies have shown that HERV-derived elements are actually involved in physiological phenomena and certain diseases including cancers. Among the various physiological phenomena related to HERV-derived elements, it is necessary to focus on inflammatory response. HERV-derived elements have been reported to be directly involved in various inflammatory diseases, including autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, amyotrophic lateral sclerosis, and Sjogren's syndrome. As a mechanism for regulating inflammation through HERV-derived elements, the possibility that HERV-derived elements may cause nonspecific innate immune processes and that HERV-derived RNA or proteins may cause selective signaling mechanisms through specific receptors can be considered. However, the mechanism through which HERV-derived elements regulate inflammatory response, such as how silent HERV elements are activated in inflammatory response and what factors and signaling mechanisms are involved in HERV-derived elements, have not been identified to date, making it difficult to study the onset of HERV-related inflammatory disease. In this review, we introduce HERV-related autoimmune diseases and propose the mechanisms of HERV-derived elements at the molecular level of HERV in inflammatory response.

Waterproofing Mechanism of Hardened Cement Paste with Waterproofing Materials (구체방수제가 혼입된 시멘트 경화체의 방수 메카니즘)

  • Kang, Hyun Ju;Song, Myong Shin;Park, Jong Hun;Jeon, Se Hoon;Lee, Sung Hyun
    • Journal of the Korean Ceramic Society
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    • v.50 no.1
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    • pp.25-30
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    • 2013
  • The pore volume of hardened cement with waterproofing materials is lower compared to that of hardened cement without waterproofing materials. Thus, fewer gaps will appear by means of chemical reactions between $Ca^{2+}$ ions in hardened cement and water, solutes, and other ions. Due to the selective permeability, the osmotic pressure of hardened cement can change due to physical effects such as the reduction of the pore volume and the reduction in the number of pores, as well as by the electrochemical reaction between water, solutes, other ions and $Ca^{2+}$ ions in hardened cement. Of course, these factors do not have independent effects but instead a combined complex effect. Accordingly, we studied changes in the osmotic pressure due to the difference in the pore structure of hardened cement. A pore size smaller than 1 nm in hardened cement had only a slight effect on the osmotic pressure, whereas a pore size larger than 1 nm had a direct effect on the osmotic pressure.

Radio-Iodinated arbutin for tumor imaging

  • Huynh, Phuong Tu;Ha, Yeong Su;Lee, Woonghee;Yoo, Jeongsoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.3 no.2
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    • pp.72-79
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    • 2017
  • Arbutin is a hydroquinone derivative with a glucose moiety. As a tyrosinase inhibitor, it is widely used as a skin-whitening cosmetic agent for the treatment of cutaneous hyperpigmentary disorders, such as melasma and freckles. In the medical field, many studies have addressed the use of arbutin in various tumors, but the mechanism for tumor uptake of arbutin is still unclear. In this paper, we radiolabeled arbutin using radioiodine and studied its pharmacokinetics and tumor uptake via biodistribution experiments and single-photon emission computed tomography (SPECT) imaging. Radiolabeled $^{131}I-arbutin$ was stable for up to 24 h in PBS and serum. Biodistribution studies and SPECT imaging indicated high uptake of the compound in the bladder and kidneys shortly after injection. Twenty-four hours post-injection, significant deiodination was observed. Apart from high thyroid uptake, selective tumor uptake was clearly observed. The tumor-to-muscle and tumor-to-blood ratios were 26 and 9, respectively.

Arachidonic Acid Mediates Apoptosis Induced by N-Ethylmaleimide in HepG2 Human Hepatoblastoma Cells

  • Lee, Yong-Soo
    • Biomolecules & Therapeutics
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    • v.17 no.4
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    • pp.379-387
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    • 2009
  • We have previously reported that N-ethylmaleimide (NEM) induces apoptosis through activation of $K^+$, $Cl^-$-cotransport (KCC) in HepG2 human hepatoblastoma cells. In this study we investigated the possible role of phospholipase $A_2$ ($PLA_2$)-arachidonic acid (AA) signals in the mechanism of the NEM-induced apoptosis. In these experiments we used arachidonyl trifluoromethylketone ($AACOCF_3$), bromoenol lactone (BEL) and p-bromophenacyl bromide (BPB) as inhibitors of the calcium-dependent cytosolic $PLA_2$ ($cPLA_2$), the calcium-independent $PLA_2$ ($iPLA_2$) and the secretory $PLA_2$ ($sPLA_2$), respectively. BEL significantly inhibited the NEM-induced apoptosis, whereas $AACOCF_3$ and BPB did not. NEM increased AA liberation in a dose-dependent manner, which was markedly prevented only by BEL. In addition AA by itself induced $K^+$ efflux, a hallmark of KCC activation, which was comparable to that of NEM. The NEM-induced apoptosis was not significantly altered by treatment with indomethacin (Indo) and nordihydroguaiaretic acid (NDGA), selective inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX), respectively. Treatment with AA or 5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolizable analogue of AA, significantly induced apoptosis. Collectively, these results suggest that AA liberated through activation of $iPLA_2$ may mediate the NEMinduced apoptosis in HepG2 cells.

TOXIC MECHANISM OF Ro09-0198 ISOLATED FROM STREPTOVERTICILLIUM (Ro 09-0198의 독성발현 기전에 관한 연구)

  • Choung, Se-Young
    • Toxicological Research
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    • v.6 no.1
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    • pp.109-119
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    • 1990
  • Ro09-0198, a cyclic peptide isolated from culture filtrates of Streptoverticillium griseoverticillatum, induced lysis of erythrocytes. Ro-09-0198-induced hemolysis was temperature-dependent and the sensitivity of hemolysis differed greatly among animal species. Preincubation of the peptide with phosphatidylethanolamine reduced the hemolytic activity, whereas other phospholipids present in erythrocytes in nature had no effect. A study of the structural requirements on phosphatidylethanolamine necessary for interaction with the peptide indicates that Ro09-0198 recognizes strictly a particular chemical structure of phosphatidylethanolamine: dialkylphosphoethanolamine as well as 1-acylglycerophosphoethanolamine showed the same inhibitory effct on hemolysis induced by Ro09-0198 as diacylphosphatidyl-ethanolamine, whereas phosphoethanolamine gave no inhibitory effect. Neither phosphatidyl-N-monomethylethanolamine nor alkylphosphopropanolamine had an inhibitory effect. Proton resonances of the peptide were observed in dimethyl sulfoxide solution in the presence of 1-dodecanoyl-sn-glycerophosphoethanolamine. This peptide caused permeability increase and aggregation of liposomes containing phosphatidylethanolamine. A glycerol backbone and a primary amino group of phosphatidylethanolamine are necessary for interaction with Ro09-0198 to cause membrane damage. Ro09-0198 induced a selective permeability change on liposomes. Glucose and umbelliferyl phosphate were effluxed significantly, but sucrose was only slightly permeable and inulin could not be released. Platelet aggregation and serotonin release simultaneously induced by Ro09-0198. Addition of peptide to rat platelet, loaded with the fluorescent $Ca^{++}$ chelator quin-2, caused immediate rise in cytosolic free $Ca^{++}$ to liposomal membrane containing phosphatidylethanolamine was observed dose dependently.

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Neurobiological Effects of Methamphetamine Abuse on Neurotransmitters: A Review (흥분제(Psychostimulants)에 대한 신경생물학 측면의 고찰 -Methamphetamine 남용을 중심으로)

  • Lee Tae Kyung;Jon E. Grant;Kim, Suck Won;Oh Dong Yul
    • Journal of The Korean Society of Clinical Toxicology
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    • v.1 no.1
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    • pp.21-26
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    • 2003
  • Methamphetamine (MA) is a major drug of abuse in Korea. Currently preliminary evidence suggests that MA dependence may cause long-term neural damage in human. Repeated exposure to psychostimulants such as methamphetamine results in behavioral sensitization, a paradigm thought to be relevant to drug craving and addiction in human. Sensitization alters neural circuitry involved in normal processes of incentrive, motivation, and reward. However the precise mechanism of this behavioral sensitization has not yet been fully elucidated. Repeated use of high dose MA causes neurotoxicity which is characterized by a long-lasting depletion of striatal dopamine (DA) and tyrosin hydroxylase activity of DA, DA-transporter binding sites in the striatum. The loss of DA transporters correlates with memory problems and lack of motor coordination. DA fuels motivation and pleasure, but it' s also crucial for learning and movement. This selective review provides a summary of studies that assess the neurobiological mechanisms of MA.

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