• 제목/요약/키워드: Selective Mechanism

검색결과 442건 처리시간 0.02초

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

  • 신혜란;차영덕;한정욱;윤정원;김부성;송장호
    • The Korean Journal of Pain
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    • 제20권2호
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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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    • 제20권4호
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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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    • 제63권6호
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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.

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

  • 염광욱
    • 한국가스학회지
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    • 제26권2호
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    • pp.21-26
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    • 2022
  • 사륜구동은 구동력을 4바퀴에 모두 전달하기 때문에 노면과의 접지력이 상승하여 구동력이 상승한다. 하지만 그로 인해 연비가 저하되는 단점을 가지고 있다. 따라서 평소에 이륜구동으로 주행하다가 필요에 의해 선택적 사륜구동으로 변환하는 방법으로 사륜구동을 많이 사용한다. 이러한 선택적 사륜구동은 운전자가 보내는 전기적 신호를 Transfer case에서 기계적으로 바꿔서 구동력을 변환시킨다. 본 연구에서는 전기적 신호를 기계적으로 바꿔주기 위해 모터에 감속기를 적용하여 토크를 증대시켜 기능을 수행하였다. 따라서, 본 연구에서는 구동을 변환시켜주기 위해 적용되는 Transfer case내부에 있는 모터에 적용할 수 있는 감속메커니즘을 도출하고 그에 따른 유성기어형태를 적용한 감속비를 최적화하였다. 그리고 도출된 감속비를 토대로 링기어를 공통으로 사용하는 유성기어 2세트를 적용하여 입력축과 출력축이 동일상에서 감속이 진행되는 유성기어 기어치형의 개발 및 Transfer csae 내에 있는 구동변환장치 구동부의 최적화 설계를 진행하였다.

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

  • 고은지;차희재
    • 생명과학회지
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    • 제31권8호
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    • pp.771-777
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    • 2021
  • 인간 내생 레트로바이러스(Human Endogenous Restrovirus, HERV)는 수백만년전 인간의 유전체에 삽입되었으며 이후 오랜 세월을 거치며 재조합, 결실 및 돌연변이 등 여러 원인에 의해 더 이상 활성화된 바이러스로 역할을 하지 못하고 감염되지 않는다. 하지만 HERV는 최근 연구들은 HERV 유래 인자들이 실제 생리현상 및 암을 비롯한 특정 질환에 관여 하고 있다는 것을 보여 주었다. HERV와 관련된 여러가지 생리 현상 중 염증반응에 초점을 맞추어 고찰해 볼 필요가 있다. HERV는 류마티스, 다발성 경화증, 근위축성 측삭경화증, 쇼그렌 증후군 같은 자가면역질환을 비롯한 여러 염증질환에 직접적으로 관여하는 것으로 보고 되고 있다. HERV의 염증 조절 기작으로는 HERV 유래 인자들이 비특이적 선천성 면역과정을 유발할 가능성과 HERV 유래의 RNA와 단백질이 특정 수용체를 통해 선택적 신호전달기작을 유발할 가능성을 고려 할 수 있다. 하지만 어떠한 방식으로 잠재되어 있던 HERV가 염증반응에서 활성화 되는지 또한 HERV와 관여된 인자들과 신호기작들이 어떠한 것들이 있는지 등 HERV의 인자들이 염증반응을 조절하는 기작에는 아직 많은 것들이 밝혀지지 않아 질병 발병에 대한 연구에 어려움이 있는 실정이다. 본 리뷰에서는 HERV 관련 자가 면역질환을 소개하고 염증반응 조절 기작에 관한 HERV의 분자수준에서의 작용 메커니즘을 제안 하고자 한다.

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

  • 강현주;송명신;박종헌;전세훈;이성현
    • 한국세라믹학회지
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    • 제50권1호
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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
    • 대한방사성의약품학회지
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    • 제3권2호
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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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    • 제17권4호
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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.

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

  • 정세영
    • Toxicological Research
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    • 제6권1호
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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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흥분제(Psychostimulants)에 대한 신경생물학 측면의 고찰 -Methamphetamine 남용을 중심으로 (Neurobiological Effects of Methamphetamine Abuse on Neurotransmitters: A Review)

  • 이태경;존 E 그랜트;김석원;오동열
    • 대한임상독성학회지
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    • 제1권1호
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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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