• Title/Summary/Keyword: mechanisms of action

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Crosstalk and Interplay between the Ubiquitin-Proteasome System and Autophagy

  • Ji, Chang Hoon;Kwon, Yong Tae
    • Molecules and Cells
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    • v.40 no.7
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    • pp.441-449
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    • 2017
  • Proteolysis in eukaryotic cells is mainly mediated by the ubiquitin (Ub)-proteasome system (UPS) and the autophagy-lysosome system (hereafter autophagy). The UPS is a selective proteolytic system in which substrates are recognized and tagged with ubiquitin for processive degradation by the proteasome. Autophagy is a bulk degradative system that uses lysosomal hydrolases to degrade proteins as well as various other cellular constituents. Since the inception of their discoveries, the UPS and autophagy were thought to be independent of each other in components, action mechanisms, and substrate selectivity. Recent studies suggest that cells operate a single proteolytic network comprising of the UPS and autophagy that share notable similarity in many aspects and functionally cooperate with each other to maintain proteostasis. In this review, we discuss the mechanisms underlying the crosstalk and interplay between the UPS and autophagy, with an emphasis on substrate selectivity and compensatory regulation under cellular stresses.

Effects of Ginseng Total Saponins on the Analgesia and Tolerance Development of Pentazocine (펜타조신의 진통작용 및 내성형성에 미치는 인삼 사포닌의 효과)

  • Kim, Hack-Seang;Ann, Sun-Hee;Seong, Yeon-Hee;Kim, Sun-Hye;Oh, Ki-Wan
    • Journal of Ginseng Research
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    • v.16 no.2
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    • pp.93-98
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    • 1992
  • This study examined the Influence of ginseng total saponins (GTS) on the analgestic action and tolerance development of pentazocine in mice. Pentazocine prolonged the latency to response in the tail flick rather than in the tail pinch test. The analgesic effect of pentaEocine was antagonized by naloxone and completely eliminated by pretreatment u·ith f-chlorophenylalanine (PCPA). GTS provented the pentasocine-incuced analgesia ann inhibited the development of tolerance to pentazocine. The antagonistic effect of GTS on the pentazocine-induced analgesia was abolished by 5-HTP, but not by L-DOPA. These results suggest that GTS inhibits the analgesic action of pentazocine by the interaction with serotonergic neuron.

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Exploring the Mechanisms and Target Diseases of Sasang Constitutional Prescription based on Multiscale Interactome (다계층 상호작용 네트워크 기반 사상처방의 작용 기전과 대상 질환 탐색 연구)

  • Won-Yung Lee;Ji Hwan Kim
    • Journal of Sasang Constitutional Medicine
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    • v.35 no.4
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    • pp.10-22
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    • 2023
  • Objectives The aim of this study is to explore the mechanism of action and target diseases of Sasang constitutional prescriptions using a multiscale interactome approach. Methods The compound and target information of Sasang constitutional prescriptions were retrieved from various databases such as the TM-MC, STITCH, and TTD. Key targets for Sasang constitutional prescriptions were identified by selecting the top 100 targets based on the number of simple paths within the constructed network. Diffusion profiles for Sasang constitutional prescriptions and diseases were calculated based on a biased random walk algorithm. Potential diseases and key mechanisms of Sasang constitutional prescriptions were identified by analyzing diffusion profiles. Results We identified 144 Sasang constitutional prescriptions and their targets, finding 80 herbs with effective biological targets. A cluster analysis based on selecting up to 100 key targets for each prescription revealed a more cohesive grouping of prescriptions according to Sasang constitution. We then predicted potential diseases for 62 Sasang constitutional prescriptions using diffusion profiles calculated on a multiscale interactome. Finally, our analysis of diffusion profiles revealed key targets and biological functions of prescriptions in obesity and diabetes. Conclusions This study demonstrates the effectiveness of a multiscale interactome approach in elucidating the complex mechanisms and potential therapeutic applications of prescriptions in Sasang constitutional medicine.

Improvement of Biological Control against Bacterial Wilt by the Combination of Biocontrol Agents with Different Mechanisms of Action

  • Kim, Ji-Tae;Kim, Shin-Duk
    • Journal of Applied Biological Chemistry
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    • v.50 no.3
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    • pp.136-143
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    • 2007
  • Despite the increased interests in biological control of soilborne diesease for environmental protection, biological control of bacterial wilt caused by Ralstonia solanacearum have not provided consistent or satisfying results. To enhance the control efficacy and reducing the inconsistency and variability, combinations of specific strains of microorganisms, each having a specific mechanism of control, were applied in this study. More than 30 microorganisms able to reduce the activity of pathogen by specific mechanism of action were identified and tested for their disease suppressive effects. After in vitro compatibility examinations, 21 individual strains and 15 combinations were tested in the greenhouse. Results indicated three-way combinations of different mode of control, TS3-7+A253-16+SKU78 and TS1-5+A100-1+SKU78, enhanced disease suppression by 70%, as compared to 30-50% reduction for their individual treatments. This work suggests that combining multiple traits antagonizing the pathogen improve efficacy of the biocontrol agents against Ralstonia solanacearum.

Glucose Transporters and Insulin Action : Some Insights into Diabetes Management

  • Jung, Chan-Y.;Lee, Wan
    • Archives of Pharmacal Research
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    • v.22 no.4
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    • pp.329-334
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    • 1999
  • Insulin stimulates glucose uptake in muscle and adipose cells primarily by recruiting GLUT4 from an intracellular storage pool to the plasma membrane. Dysfunction of this process known as insulin resistance causes hyperglycemia, a hallmark of diabetes and obesity. Thus the understanding of the mechanisms underlying this process at the molecular level may give an insight into the prevention and treatment of these health problems. GLUT4 in rat adipocytes, for example, constantly recycles between the cells surface and an intracellular pool by endocytosis and exocytosis, each of which is regulated by an insulin-sensitive and GLUT4-selective sorting mechanism. Our working hypothesis has been that this sorting mechanism includes a specific interaction of a cytosolic protein with the GLUT4 cytoplasmic domain. Indeed, a synthetic peptide of the C-terminal cytoplasmic domain of GLUT4 induces an insulin-like GLUT4 recruitment when introduced in rat adipocytes. Relevance of these observations to a novel euglycemic drug design is discussed.

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Narrative Review on the Mechanism of Whidam's Vibrator Sugi Therapy (휘담식 진동기 수기요법의 기전에 대한 서술적 고찰)

  • Hun Mo Ahn;Dae Sung Jung;Han Joo Kang
    • Journal of Korean Medical Ki-Gong Academy
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    • v.22 no.1
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    • pp.1-27
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    • 2023
  • Objective : This paper provides a narrative review of the research literature on the neurophysiological and neurochemical mechanisms of local vibration while studying the treatment principles and mechanisms of Whidam's vibrator Sugi therapy. Methods : Searches related to vibration therapy research were conducted in PUBMED using "Vibration", "Whole Body Vibration", "Localized Vibration", and "Focal Vibration". The Conditions were limited to review and systematic review. Results : Roberto Casale's paper was selected as an inquiry task and reviewed critically and narratively by referring to other papers. The stimulation process of local vibration (LV) was broadly classified into receptor transmission (pain reception phase), ascending sensory pathway to the spinal cord (segmental phase), and action of the cortex and subcortical structures (systemic control phase) according to the pain pathway. In addition, the role of C-tactile mechanoreceptors, changes in neurotransmitters and neurohormones, LV stimulation below perception threshold (lower threshold), pain control and kinesiologic illusions were specially addressed. In addition, the expression and function of Piezo Channels were added to supplement the human pain and tactile sensing mechanism. Conclusions : LV exerts pain control mechanisms through different interactions that can interfere with pain transmission and pain perception. Since LV provides sufficient neurophysiological reasons for clinical application, it is necessary to expand the use of Whidam's vibrator Sugi therapy to a wider range of clinical applications.

FLUORESCENCE QUENCHING OF BBOT BY ANILINE IN DIFFERENT ORGANIC SOLVENTS

  • Kadadevarmath, J.S.;Giraddi, T.P.;Chikkur, G.C.
    • Journal of Photoscience
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    • v.4 no.3
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    • pp.105-112
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    • 1997
  • The fluorescence quenching of 2, 5-di-(5-tert-butyl-2-benzoxazolyl)-thiophene (BBOT) by aniline in five different solvents namely heptane, hexane, cyclohexane, dioxane and acetonitrile has been carried out at room temperature with a view to understand the quenching mechanisms. The experimental results show positive deviation in the Stern-Volmer plots in all the solvents. In order to interpret these results we have invoked the Ground state complex and sphere of action static quenching models. Using these models various rate parameters have been determined. The magnitudes of these parameters suggest that sphere of action static quenching model agrees well with the experimental results. Hence this positive deviation is attributed to the static and dynamic quenching. Further, with the use of Finite Sink approximation model, it was possible to check these bimolecular reactions as diffusion-limited and to estimate independently distance parameter R$^1$ and mutual diffusion coefficient D. Finally an attempt has been made to correlate the values of R$^1$ and D with the values of the encounter distance R and the mutual diffusion coefficient D determined using the Edward's empirical relation and Stokes-Einstein relation.

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Action Mechanism of Enhancers for Activating Gene Transcription

  • Yea Woon Kim;AeRi Kim
    • Biomedical Science Letters
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    • v.29 no.3
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    • pp.103-108
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    • 2023
  • Enhancers are cis-elements to regulate transcription of cell/tissue-specific genes in multicellular organisms. These elements locate in upstream or downstream regions of target genes and are found in a long distance up to 100 Kb in some cases. Transcription factors and coactivators bind to enhancers in a chromatin environment. Enhancers appear to facilitate the transcription of target genes by communicating with promoters and activating them. As transcription activation mechanism of enhancers, chromatin looping between enhancers and promoters, tracking of enhancer activity to promoters along the intervening regions, and movement of enhancers and promoters into transcription condensates have been suggested based on various molecular and cellular biology studies. These mechanisms are likely to act together rather than exclusive each other for gene transcription. Understanding of enhancer action mechanism may provide a way to regulate the transcription of cell/tissue-specific genes relating with aging or various diseases.

Consideration of the Exterior Syndrome Caused by External Pathogen (wind-cold-dampness) (외사(外邪)(풍한습사(風寒濕邪))에 의한 외감표증(外感表證)의 발병기전(發病機轉)에 대한 소고)

  • Lee, Sang-Ryong;Lee, Chang-Hyun;Lee, Kwang-Gye
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.4
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    • pp.409-417
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    • 2012
  • External pathogens such as wind, cold can easily invade the external parts of the body when host's external defense ability is not secure. Herein, we consider the underlying mechanisms against the external contraction at the body surface. During the early period after primary invasion, external defense mechanisms are gradually activated. The classic clinical manifestations are aversion to cold, fever, headache, generalized pain, and nasal congestion. This condition is called by invasion of external pathogen into the body surface. As the disease progress, lung qi is stagnated and thereby up-outward and downward movement action of lung become disturbed. Therefore, when doctor administrate formula to treat the exterior syndrome, doctor must keep in mind not only materia medica, but also underlying mechanisms through which many clinical symptoms appear.

Dehydropolycondensation of Aminophenols under the Catalytic Acition of Metallic Chelate Compounds (Ⅲ) Reactions of the Isomers, Reaction Mechanisms, and the Structures of the Oligomers (金屬킬레이트 化合物의 觸媒作用에 依한 Aminophenol 類의 酸化的 重縮合反應 (Ⅲ) 異性體의 反應, 反應機構 및 生成物의 構造)

  • Choi, Kyu-Suck
    • Journal of the Korean Chemical Society
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    • v.12 no.3
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    • pp.128-137
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    • 1968
  • In the oligomerization of p-aminophenol by the catalytic action of Fe-EDTA complex in the aqueous medium, the mixed complex intermediate, Fe-EDTA-M type, is considered to be formed, from which active radicals of the monomer are produced. In this system, polymerization is presumed to proceed as follows: Free radical formation ${\to}$ Coupling ${\to}$ Activation ${\to}$ Coupling, and so on. In this study, the form of the monomer and coordination state in the mixed complex, the catalytic action of Fe-EDTA the complex, the reaction mechanism, and the structure of the oligomers are discussed.

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