• Title/Summary/Keyword: therapeutic target

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The role of cap-assisted endoscopy and its future implications

  • Sol Kim;Bo-In Lee
    • Clinical Endoscopy
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    • 제57권3호
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    • pp.293-301
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    • 2024
  • Cap-assisted endoscopy refers to a procedure in which a short tube made of a polymer (mostly transparent) is attached to the distal tip of the endoscope to enhance its diagnostic and therapeutic capabilities. It is reported to be particularly useful in: (1) minimizing blind spots during screening colonoscopy, (2) providing a constant distance from a lesion for clear visualization during magnifying endoscopy, (3) accurately assessing the size of various gastrointestinal lesions, (4) preventing mucosal injury during foreign body removal, (5) securing adequate workspace in the submucosal space during endoscopic submucosal dissection or third space endoscopy, (6) providing an optimal approach angle to a target, and (7) suctioning mucosal and submucosal tissue with negative pressure for resection or approximation. Here, we review various applications of attachable caps in diagnostic and therapeutic endoscopy and their future implications.

혈중 목표 농도 자동 조절기(TCI) 개발 PART1 : 약동학적 모델의 수립과 검증 (Development of Target-Controlled Infusion System in Plasma Concentration. PART1 : Establishment of Pharmacokinetic Model and Verification)

  • 안재목;길호영
    • 대한의용생체공학회:의공학회지
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    • 제23권5호
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    • pp.341-349
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    • 2002
  • 본 논문에서는 혈중 목표 농도 자동 조절기(Target-controlled infusion system. TCI)를 개발하는 것으로써, 마취의가 혈중 목표 농도를 설정하면 사용약제의 약동학적 모델링에 의해서 주입속도를 자동적으로 계산하여 마취의 깊이를 예측하는 약동학적 모델의 수립과 검증 방법을 설명한다. 정확한 약동학적 모델의 구축은 시스템의 성능에 큰 영향을 미치므로 먼저 PART 1에서는 약동학적 모델을 구축하되 3-콤파트먼트 모델과 4-콤파트먼트 모델로 해석하였다. 기존의 TCI에서 사용하고 있는 3-콤파트먼트 모델에 가상의 효과처 구획(Effect Site Compartment)을 만들고 이를 네 버내 구획으로 가정한 4-콤파트먼트 모델(Four-Compartment Model)을 수립하였고, matlab 5.0을 이용하여 비교 분석하였다. 모델은 혈중 목표 농도 주입(Plasma Targeting)과 효과처 목표 농도 주입(Effect Site Targeting), 혈중 농도 유지를 위한 주입율 계산과 기타 마취 상태를 추정하는 정보를 포함한다. 시뮬레이션의 결과를 바탕으로 4-콤파트먼트 모델을 디지털 z-변환을 거쳐 디지털시그널프로세서에 프로그램하고 TCI시스템의 적용가능성을 평가하였다. 정맥 마취용 TCI는 오동작에 대한 검증이 반드시 요구되므로 구축한 모델링에 대한 시뮬레이션의 평가 방법을 설정하였다. 기존의 TCI시스템과는 달리 약동학적 약물 전달 속도 상수(k-파라미터)를 독립적으로 조절할 수 있는 기능이 추가되어 다양한 약제의 사용이 가능할 뿐만 아니라 새로운 약동학적 모델의 개발과 평가에 기여하게 되고, 환자의 체형과 병명에 따른 약동학적 모델의 변화에 대응할 수 있게 하였다.

Target engagement of ginsenosides in mild cognitive impairment using mass spectrometry-based drug affinity responsive target stability

  • Zhu, Zhu;Li, Ruimei;Qin, Wei;Zhang, Hantao;Cheng, Yao;Chen, Feiyan;Chen, Cuihua;Chen, Lin;Zhao, Yunan
    • Journal of Ginseng Research
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    • 제46권6호
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    • pp.750-758
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    • 2022
  • Background: Mild cognitive impairment (MCI) is a transitional condition between normality and dementia. Ginseng is known to have effects on attenuating cognitive deficits in neurogenerative diseases. Ginsenosides are the main bioactive component of ginseng, and their protein targets have not been fully understood. Furthermore, no thorough analysis is reported in ginsenoside-related protein targets in MCI. Methods: The candidate protein targets of ginsenosides in brain tissues were identified by drug affinity responsive target stability (DARTS) coupled with label-free liquid chromatography-mass spectrometry (LC-MS) analysis. Network pharmacology approach was used to collect the therapeutic targets for MCI. Based on the above-mentioned overlapping targets, we built up a proteineprotein interaction (PPI) network in STRING database and conducted gene ontology (GO) enrichment analysis. Finally, we assessed the effects of ginseng total saponins (GTS) and different ginsenosides on mitochondrial function by measuring the activity of the mitochondrial respiratory chain complex and performing molecular docking. Results: We screened 2526 MCI-related protein targets by databases and 349 ginsenoside-related protein targets by DARTS. On the basis of these 81 overlapping genes, enrichment analysis showed the mitochondria played an important role in GTS-mediated MCI pharmacological process. Mitochondrial function analysis showed GTS, protopanaxatriol (PPT), and Rd increased the activities of complex I in a dose-dependent manner. Molecular docking also predicted the docking pockets between PPT or Rd and mitochondrial respiratory chain complex I. Conclusion: This study indicated that ginsenosides might alleviate MCI by targeting respiratory chain complex I and regulating mitochondrial function, supporting ginseng's therapeutic application in cognitive deficits.

Triptolide Inhibits Histone Methyltransferase EZH2 and Modulates the Expression of Its Target Genes in Prostate Cancer Cells

  • Tamgue, Ousman;Chai, Cheng-Sen;Hao, Lin;Zambe, John-Clotaire Daguia;Huang, Wei-Wei;Zhang, Bin;Lei, Ming;Wei, Yan-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권10호
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    • pp.5663-5669
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    • 2013
  • The histone methyltransferase EZH2 (enhancer of zeste homolog 2) plays critical roles in prostate cancer (PCa) development and is a potential target for PCa treatment. Triptolide possesses anti-tumor activity, but it is unknown whether its therapeutic effect relates with EZH2 in PCa. Here we described EZH2 as a target for Triptolide in PCa cells. Our data showed that Triptolide suppressed PCa cell growth and reduced the expression of EZH2. Overexpression of EZH2 attenuated the Triptolide induced cell growth inhibition. Moreover, Triptolide treatment of PC-3 cells resulted in elevated mRNA levels of target genes (ADRB2, CDH1, CDKN2A and DAB2IP) negatively regulated by EZH2 as well as reduced mRNA levelsan of EZH2 positively regulated gene (cyclin D1). Our findings suggest the PCa cell growth inhibition mediated by Triptolide might be associated with downregulation of EZH2 expression and the subsequent modulation of target genes.

네트워크 약리학 기반 대황목단피탕(大黃牧丹皮湯)의 건선 조절 효능 및 작용 기전 예측 (Prediction the efficacy and mechanism of action of Daehwangmokdanpitang to treat psoriasis based on network pharmacology)

  • 권빛나;김동욱;양갑식;조일주
    • 대한본초학회지
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    • 제38권6호
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    • pp.73-91
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    • 2023
  • Objectives : This study used a network pharmacology approach to elucidate the efficacy and molecular mechanisms of Daehwangmokdanpitang (DHMDPT) on Psoriasis. Methods : Using OASIS databases and PubChem database, compounds of DHMDPT and their target genes were collected. The putative target genes of DHMDPT and known target genes of psoriasis were compared and found the correlation. Then, the network was constructed using Cytoscape 3.10.1. The key target genes were screened by Analyzer network and their functional enrichment analysis was conducted based on the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms. Results : The result showed that total 30 compounds and 439 related genes were gathered from DHMDPT. 264 genes were interacted with psoriasis gene set, suggesting that the effects of DHMDPT are closely related to psoriasis. Based on GO enrichment analysis and KEGG pathways, 'Binding', 'Cytokine Activity', 'Receptor Ligand Activity' 'HIF-1 signaling pathway', 'IL-17 signaling pathway', 'Toll-like receptor signaling pathway', and 'TNF signaling pathway' were predicted as functional pathways of 16 key target genes of DHMDPT on psoriasis. Among the target genes, IL6, IL1B, TNF, AKT1 showed high correlation with the results of KEGG pathways. Additionally, Emodin, Acetovanillone, Gallic acid, and Ferulic acid showed a high relevance with key genes and their mechanisms. Conclusion : Through a network pharmacological method, DHMDPT was predicted to have high relevance with psoriasis. This study could be used as a basis for studying therapeutic effects of DHMDPT on psoriasis.

AMP-activated protein kinase: An emerging target for ginseng

  • Jeong, Kyong Ju;Kim, Go Woon;Chung, Sung Hyun
    • Journal of Ginseng Research
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    • 제38권2호
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    • pp.83-88
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    • 2014
  • The adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of cellular energy. Once activated, it switches on catabolic pathways generating adenosine triphosphate (ATP), while switching off biosynthetic pathways consuming ATP. Pharmacological activation of AMPK by metformin holds a therapeutic potential to reverse metabolic abnormalities such as type 2 diabetes and nonalcoholic fatty liver disease. In addition, altered metabolism of tumor cells is widely recognized and AMPK is a potential target for cancer prevention and/or treatment. Panax ginseng is known to be useful for treatment and/or prevention of cancer and metabolic diseases including diabetes, hyperlipidemia, and obesity. In this review, we discuss the ginseng extracts and ginsenosides that activate AMPK, we clarify the various mechanisms by which they achieve this, and we discuss the evidence that shows that ginseng or ginsenosides might be useful in the treatment and/or prevention of metabolic diseases and cancer.

Human-yeast genetic interaction for disease network: systematic discovery of multiple drug targets

  • Suk, Kyoungho
    • BMB Reports
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    • 제50권11호
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    • pp.535-536
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    • 2017
  • A novel approach has been used to identify functional interactions relevant to human disease. Using high-throughput human-yeast genetic interaction screens, a first draft of disease interactome was obtained. This was achieved by first searching for candidate human disease genes that confer toxicity in yeast, and second, identifying modulators of toxicity. This study found potentially disease-relevant interactions by analyzing the network of functional interactions and focusing on genes implicated in amyotrophic lateral sclerosis (ALS), for example. In the subsequent proof-of-concept study focused on ALS, similar functional relationships between a specific kinase and ALS-associated genes were observed in mammalian cells and zebrafish, supporting findings in human-yeast genetic interaction screens. Results of combined analyses highlighted MAP2K5 kinase as a potential therapeutic target in ALS.

Therapeutic aptamers: developmental potential as anticancer drugs

  • Lee, Ji Won;Kim, Hyun Jung;Heo, Kyun
    • BMB Reports
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    • 제48권4호
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    • pp.234-237
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    • 2015
  • Aptamers, composed of single-stranded DNA or RNA oligonucleotides that interact with target molecules through a specific three-dimensional structure, are selected from pools of combinatorial oligonucleotide libraries. With their high specificity and affinity for target proteins, ease of synthesis and modification, and low immunogenicity and toxicity, aptamers are considered to be attractive molecules for development as anticancer therapeutics. Two aptamers - one targeting nucleolin and a second targeting CXCL12 - are currently undergoing clinical trials for treating cancer patients, and many more are under study. In this mini-review, we present the current clinical status of aptamers and aptamer-based cancer therapeutics. We also discuss advantages, limitations, and prospects for aptamers as cancer therapeutics. [BMB Reports 2015; 48(4): 234-237]

MicroRNAs as critical regulators of the endothelial to mesenchymal transition in vascular biology

  • Kim, Jongmin
    • BMB Reports
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    • 제51권2호
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    • pp.65-72
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    • 2018
  • The endothelial to mesenchymal transition (EndMT) is a newly recognized, fundamental biological process involved in development and tissue regeneration, as well as pathological processes such as the complications of diabetes, fibrosis and pulmonary arterial hypertension. The EndMT process is tightly controlled by diverse signaling networks, similar to the epithelial to mesenchymal transition. Accumulating evidence suggests that microRNAs (miRNAs) are key regulators of this network, with the capacity to target multiple messenger RNAs involved in the EndMT process as well as in the regulation of disease progression. Thus, it is highly important to understand the molecular basis of miRNA control of EndMT. This review highlights the current fund of knowledge regarding the known links between miRNAs and the EndMT process, with a focus on the mechanism that regulates associated signaling pathways and discusses the potential for the EndMT as a therapeutic target to treat many diseases.

Nucleic Acid Aptamers: New Methods for Selection, Stabilization, and Application in Biomedical Science

  • Kong, Hoon Young;Byun, Jonghoe
    • Biomolecules & Therapeutics
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    • 제21권6호
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    • pp.423-434
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    • 2013
  • The adoption of oligonucleotide aptamer is well on the rise, serving an ever increasing demand for versatility in biomedical field. Through the SELEX (Systematic Evolution of Ligands by EXponential enrichment), aptamer that can bind to specific target with high affinity and specificity can be obtained. Aptamers are single-stranded nucleic acid molecules that can fold into complex three-dimensional structures, forming binding pockets and clefts for the specific recognition and tight binding of any given molecular target. Recently, aptamers have attracted much attention because they not only have all of the advantages of antibodies, but also have unique merits such as thermal stability, ease of synthesis, reversibility, and little immunogenicity. The advent of novel technologies is revolutionizing aptamer applications. Aptamers can be easily modified by various chemical reactions to introduce functional groups and/or nucleotide extensions. They can also be conjugated to therapeutic molecules such as drugs, drug containing carriers, toxins, or photosensitizers. Here, we discuss new SELEX strategies and stabilization methods as well as applications in drug delivery and molecular imaging.