• 제목/요약/키워드: translational research

검색결과 527건 처리시간 0.024초

Stem cell-derived extracellular vesicle therapy for acute brain insults and neurodegenerative diseases

  • Bang, Oh Young;Kim, Ji-Eun
    • BMB Reports
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    • 제55권1호
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    • pp.20-29
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    • 2022
  • Stem cell-based therapy is a promising approach for treating a variety of disorders, including acute brain insults and neurodegenerative diseases. Stem cells such as mesenchymal stem cells (MSCs) secrete extracellular vesicles (EVs), circular membrane fragments (30 nm-1 ㎛) that are shed from the cell surface, carrying several therapeutic molecules such as proteins and microRNAs. Because EV-based therapy is superior to cell therapy in terms of scalable production, biodistribution, and safety profiles, it can be used to treat brain diseases as an alternative to stem cell therapy. This review presents evidences evaluating the role of stem cell-derived EVs in stroke, traumatic brain injury, and degenerative brain diseases, such as Alzheimer's disease and Parkinson' disease. In addition, stem cell-derived EVs have better profiles in biocompatibility, immunogenicity, and safety than those of small chemical and macromolecules. The advantages and disadvantages of EVs compared with other strategies are discussed. Even though EVs obtained from native stem cells have potential in the treatment of brain diseases, the successful clinical application is limited by the short half-life, limited targeting, rapid clearance after application, and insufficient payload. We discuss the strategies to enhance the efficacy of EV therapeutics. Finally, EV therapies have yet to be approved by the regulatory authorities. Major issues are discussed together with relevant advances in the clinical application of EV therapeutics.

Korean Red Ginseng saponin fraction exerts anti-inflammatory effects by targeting the NF-κB and AP-1 pathways

  • Lee, Jeong-Oog;Yang, Yanyan;Tao, Yu;Yi, Young-Su;Cho, Jae Youl
    • Journal of Ginseng Research
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    • 제46권3호
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    • pp.489-495
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    • 2022
  • Background: Although ginsenosides and saponins in Korea red ginseng (KRG) shows various pharmacological roles, their roles in the inflammatory response are little known. This study investigated the anti-inflammatory role of ginsenosides identified from KRG saponin fraction (RGSF) and the potential mechanism in macrophages. Methods: The ginsenoside composition of RGSF was identified by high-performance liquid chromatography (HPLC) analysis. An anti-inflammatory effect of RGSF and its mechanisms were studied using nitric oxide (NO) and prostaglandin E2 (PGE2) production assays, mRNA expression analyses of inflammatory genes and cytokines, luciferase reporter gene assays of transcription factors, and Western blot analyses of inflammatory signaling pathways using the lipopolysaccharide (LPS)-treated RAW264.7 cells. Results: HPLC analysis identified the types and amounts of various panaxadiol ginsenosides in RGSF. RGSF reduced the generation of inflammatory molecules and mRNA levels of inflammatory enzymes and cytokines in LPS-treated RAW264.7 cells. Additionally, RGSF inhibited the signaling pathways of NF-κB and AP-1 by suppressing both transcriptional factors and signaling molecules in LPS-treated RAW264.7 cells. Conclusion: RGSF contains ginsenosides that have anti-inflammatory action via restraining the NF-κB and AP-1 signaling pathways in macrophages during inflammatory responses.

Transcriptional Heterogeneity of Cellular Senescence in Cancer

  • Junaid, Muhammad;Lee, Aejin;Kim, Jaehyung;Park, Tae Jun;Lim, Su Bin
    • Molecules and Cells
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    • 제45권9호
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    • pp.610-619
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    • 2022
  • Cellular senescence plays a paradoxical role in tumorigenesis through the expression of diverse senescence-associated (SA) secretory phenotypes (SASPs). The heterogeneity of SA gene expression in cancer cells not only promotes cancer stemness but also protects these cells from chemotherapy. Despite the potential correlation between cancer and SA biomarkers, many transcriptional changes across distinct cell populations remain largely unknown. During the past decade, single-cell RNA sequencing (scRNA-seq) technologies have emerged as powerful experimental and analytical tools to dissect such diverse senescence-derived transcriptional changes. Here, we review the recent sequencing efforts that successfully characterized scRNA-seq data obtained from diverse cancer cells and elucidated the role of senescent cells in tumor malignancy. We further highlight the functional implications of SA genes expressed specifically in cancer and stromal cell populations in the tumor microenvironment. Translational research leveraging scRNA-seq profiling of SA genes will facilitate the identification of novel expression patterns underlying cancer susceptibility, providing new therapeutic opportunities in the era of precision medicine.

Finite Element Model for Wear Analysis of Conventional Friction Stir Welding Tool

  • Hyeonggeun Jo;Ilkwang Jang;Yeong Gil Jo;Dae Ha Kim;Yong Hoon Jang
    • Tribology and Lubricants
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    • 제39권3호
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    • pp.118-122
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    • 2023
  • In our study, we develop a finite element model based on Archard's wear law to predict the cumulative wear and the evolution of the tool profile in friction stir welding (FSW) applications. Our model considers the rotational and translational behaviors of the tool, providing a comprehensive description of the wear process. We validate the accuracy of our model by comparing it against experimental results, examining both the predicted cumulative wear and the resulting changes to the tool profile caused by wear. We perform a detailed comparison between the predictions of the model and experimental data by manipulating non-dimensional coefficients comprising model parameters, such as element sizes and time increments. This comparison facilitates the identification of a specific non-dimensional coefficient condition that best replicates the experimentally observed cumulative wear. We also directly compare the worn tool profiles predicted by the model using this specific non-dimensional coefficient condition with the profiles obtained from wear experiments. Through this process, we identify the model settings that yield a tool wear profile closely aligning with the experimental results. Our research demonstrates that carefully selecting non-dimensional coefficients can significantly enhance the predictive accuracy of finite element models for tool wear in FSW processes. The results from our study hold potential implications for enhancing tool longevity and welding quality in industrial applications.

궤도 안정성에 대한 장대레일과 체결구의 민감도 (Sensitivity of the Continuous Welded Rail and the Fastener on the Track Stability)

  • 한상윤;박남회;임남형;강영종
    • 대한토목학회논문집
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    • 제26권4A호
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    • pp.719-726
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    • 2006
  • 전세계적으로 널리 사용되고 있는 장대레일 궤도는 유지 보수 비용을 절감시키고, 궤도구성요소들의 수명이 길어진다는 장점을 가지고 있다. 그러나, 혹서기에 레일의 높은 온도 상승으로 인해 장대레일 궤도에는 매우 큰 압축력이 작용하게 되고, 이는 장대레일 궤도의 장출(좌굴)을 발생시켜 열차의 탈선으로 인한 사고로 이어진다. 본 연구에서는 장대레일 궤도의 좌굴에 많은 영향을 주는 궤도의 구성요소들 중에서 레일의 단면적과 단면2차모멘트 그리고 체결구의 파손과 병진 및 회전방향의 강성이 장대레일 궤도의 좌굴에 미치는 민감도를 파악하였다.

Regulation of CMGC kinases by hypoxia

  • KyeongJin Kim;Sang Bae Lee
    • BMB Reports
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    • 제56권11호
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    • pp.584-593
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    • 2023
  • Hypoxia, a widespread occurrence observed in various malignant tumors, results from rapid tumor growth that outpaces the oxygen supply. Tumor hypoxia precipitates several effects on tumor biology; these include activating angiogenesis, intensifying invasiveness, enhancing the survival of tumor cells, suppressing anti-tumor immunity, and fostering resistance to therapy. Aligned with the findings that correlate CMGC kinases with the regulation of Hypoxia-Inducible Factor (HIF), a pivotal modulator, reports also indicate that hypoxia governs the activity of CMGC kinases, including DYRK1 kinases. Prolyl hydroxylation of DYRK1 kinases by PHD1 constitutes a novel mechanism of kinase maturation and activation. This modification "primes" DYRK1 kinases for subsequent tyrosine autophosphorylation, a vital step in their activation cascade. This mechanism adds a layer of intricacy to comprehending the regulation of CMGC kinases, and underscores the complex interplay between distinct post-translational modifications in harmonizing precise kinase activity. Overall, hypoxia assumes a substantial role in cancer progression, influencing diverse aspects of tumor biology that include angiogenesis, invasiveness, cell survival, and resistance to treatment. CMGC kinases are deeply entwined in its regulation. To fathom the molecular mechanisms underpinning hypoxia's impact on cancer cells, comprehending how hypoxia and prolyl hydroxylation govern the activity of CMGC kinases, including DYRK1 kinases, becomes imperative. This insight may pave the way for pioneering therapeutic approaches that target the hypoxic tumor microenvironment and its associated challenges.

A Nucleolar Protein, MoRRP8 Is Required for Development and Pathogenicity in the Rice Blast Fungus

  • Minji Kim;Song Hee Lee;Junhyun Jeon
    • Mycobiology
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    • 제51권5호
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    • pp.273-280
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    • 2023
  • The nucleolus is the largest, membrane-less organelle within the nucleus of eukaryotic cell that plays a critical role in rRNA transcription and assembly of ribosomes. Recently, the nucleolus has been shown to be implicated in an array of processes including the formation of signal recognition particles and response to cellular stress. Such diverse functions of nucleolus are mediated by nucleolar proteins. In this study, we characterized a gene coding a putative protein containing a nucleolar localization sequence (NoLS) in the rice blast fungus, Magnaporthe oryzae. Phylogenetic and domain analysis suggested that the protein is orthologous to Rrp8 in Saccharomyces cerevisiae. MoRRP8-GFP (translational fusion of MoRRP8 with green fluorescence protein) co-localizes with a nucleolar marker protein, MoNOP1 fused to red fluorescence protein (RFP), indicating that MoRRP8 is a nucleolar protein. Deletion of the MoRRP8 gene caused a reduction in vegetative growth and impinged largely on asexual sporulation. Although the asexual spores of DMorrp8 were morphologically indistinguishable from those of wild-type, they showed delay in germination and reduction in appressorium formation. Our pathogenicity assay revealed that the MoRRP8 is required for full virulence and growth within host plants. Taken together, these results suggest that nucleolar processes mediated by MoRRP8 is pivotal for fungal development and pathogenesis.

광 포획 향상을 위한 다중 아키텍처 식각 기술을 적용한 박막 실리콘 태양전지에 관한 연구 (A Study on Thin-Film Silicon Solar Cells with Multi-Architecture Etching Technique to Improve Light Trapping)

  • 박형기;이준신
    • 한국전기전자재료학회논문지
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    • 제37권3호
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    • pp.337-344
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    • 2024
  • This work focuses on improving the light-harvesting efficiency of thin-film silicon solar cells through innovative multi-architecture surface modifications. To create a regular optical structure, a lithographic process was performed to form it on a glass substrate through various etching processes, from Etch-1 to Etch-3. AZO was deposited on top of the structures and re-etched to create a multi-architectural surface. These surface-modified structures improved the light absorption and overall performance of the solar cell through changes in optical and physical properties, which we will analyze. In addition, we investigated the effect of post-cleaning on the etched glass structures through EDX analysis to understand the mechanism of the etching action. The results of this study are expected to provide important guidelines for the design and fabrication of solar cells and other photovoltaic devices.

A Comprehensive Review of Recent Advances in the Enrichment and Mass Spectrometric Analysis of Glycoproteins and Glycopeptides in Complex Biological Matrices

  • Mohamed A. Gab-Allah;Jeongkwon Kim
    • Mass Spectrometry Letters
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    • 제15권1호
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    • pp.1-25
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    • 2024
  • Protein glycosylation, a highly significant and ubiquitous post-translational modification (PTM) in eukaryotic cells, has attracted considerable research interest due to its pivotal role in a wide array of essential biological processes. Conducting a comprehensive analysis of glycoproteins is imperative for understanding glycoprotein bio-functions and identifying glycosylated biomarkers. However, the complexity and heterogeneity of glycan structures, coupled with the low abundance and poor ionization efficiencies of glycopeptides have all contributed to making the analysis and subsequent identification of glycans and glycopeptides much more challenging than any other biopolymers. Nevertheless, the significant advancements in enrichment techniques, chromatographic separation, and mass spectrometric methodologies represent promising avenues for mitigating these challenges. Numerous substrates and multifunctional materials are being designed for glycopeptide enrichment, proving valuable in glycomics and glycoproteomics. Mass spectrometry (MS) is pivotal for probing protein glycosylation, offering sensitivity and structural insight into glycopeptides and glycans. Additionally, enhanced MS-based glycopeptide characterization employs various separation techniques like liquid chromatography, capillary electrophoresis, and ion mobility. In this review, we highlight recent advances in enrichment methods and MS-based separation techniques for analyzing different types of protein glycosylation. This review also discusses various approaches employed for glycan release that facilitate the investigation of the glycosylation sites of the identified glycoproteins. Furthermore, numerous bioinformatics tools aiding in accurately characterizing glycan and glycopeptides are covered.

Regulation of ADAMTS-2 by 1,25-Dihydroxyvitamin D3 in Osteoblastic Cells

  • Jeon, Eun-Young;Kim, Hyun-Man;Lee, Seung-Bok
    • International Journal of Oral Biology
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    • 제31권3호
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    • pp.93-98
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    • 2006
  • Biosynthetic processing of fibrillar procollagens is essential for producing mature collagen monomers that polymerize into fibrils by a self-assembly process. The metalloproteinase ADAMTS-2 is the major enzyme that processes the N-propeptide of type I procollagen in the skin and also of type II and type III procollagens. Mutations in the ADAMTS-2 gene cause dermatospraxis in animals and Ehlers-Danlos syndrome VIIC in humans, both of which are characterized by the accumulation of type I pN-collagen and the formation of abnormal collagen fibrils in the skin. Despite its importance in procollagen processing, little is known about the regulation of ADAMTS-2 expression. Here, we demonstrate that ADAMTS-2 can be regulated by 1,25-dihydroxyvitamin D3, an inducer of type I procollagen synthesis. This steroid hormone induced ADAMTS-2 mRNA ${\sim}3-fold$ in MG-63 human osteosarcoma cells and MC3T3-E1 murine osteoblastic cells. This induction was dose- and time-dependent in MG-63 cells. In contrast, secreted ADAMTS-2 protein was increased only 1.4-fold with 1,25-dihydroxyvitamin D3. Finally, 1,25-dihydroxyvitamin D3 in the presence of ascorbate increased levels of secreted ADAMTS-2 1.9-fold over ascorbate treatment alone, which did not appreciably change ADAMTS-2 expression. These data indicate that the regulation of ADAMTS-2 is coupled with the synthesis of type I procollagen through 1,25-dihydroxyvitamin D3 signaling and may involve translational or posttranslational control.