ScholarWorks Community:
https://scholarworks.sookmyung.ac.kr/handle/2021.sw.sookmyung/278
2024-03-20T22:37:38Z
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Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/159611
Title: Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics
Authors: Bittremieux, Wout; Avalon, Nicole E.; Thomas, Sydney P.; Kakhkhorov, Sarvar A.; Aksenov, Alexander A.; Gomes, Paulo Wender P.; Aceves, Christine M.; Caraballo-Rodriguez, Andres Mauricio; Gauglitz, Julia M.; Gerwick, William H.; Huan, Tao; Jarmusch, Alan K.; Kaddurah-Daouk, Rima F.; Kang, Kyo Bin; Kim, Hyun Woo; Kondic, Todor; Mannochio-Russo, Helena; Meehan, Michael J.; Melnik, Alexey V.; Nothias, Louis-Felix; O'Donovan, Claire; Panitchpakdi, Morgan; Petras, Daniel; Schmid, Robin; Schymanski, Emma L.; van der Hooft, Justin J. J.; Weldon, Kelly C.; Yang, Heejung; Xing, Shipei; Zemlin, Jasmine; Wang, Mingxun; Dorrestein, Pieter C.
Abstract: Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect spectral library, consisting of 87,916 annotated MS/MS spectra derived from hundreds of millions of MS/MS spectra originating from published untargeted metabolomics experiments. Entries in this library, or "suspects," were derived from unannotated spectra that could be linked in a molecular network to an annotated spectrum. Annotations were propagated to unknowns based on structural relationships to reference molecules using MS/MS-based spectrum alignment. We demonstrate the broad relevance of the nearest neighbor suspect spectral library through representative examples of propagation-based annotation of acylcarnitines, bacterial and plant natural products, and drug metabolism. Our results also highlight how the library can help to better understand an Alzheimer's brain phenotype. The nearest neighbor suspect spectral library is openly available for download or for data analysis through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data. Interpreting untargeted mass spectrometry (MS) data is challenging due to incomplete reference libraries. Here, the authors created the nearest neighbor suspect spectral library from largescale public MS data, significantly enhancing the ability to hypothesize structures for unknown mass spectra.
2023-12-01T00:00:00Z
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SPC-180002, a SIRT1/3 dual inhibitor, impairs mitochondrial function and redox homeostasis and represents an antitumor activity
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/151548
Title: SPC-180002, a SIRT1/3 dual inhibitor, impairs mitochondrial function and redox homeostasis and represents an antitumor activity
Authors: Cho, Yena; Hwang, Jee Won; Park, No-June; Moon, Junghyea; Ali, Khan Hashim; Seo, Young Ho; Kim, In Su; Kim, Su-Nam; Kee, Yong
Abstract: Since sirtuins (SIRTs) are closely associated with reactive oxygen species (ROS) and antioxidant system, the development of their selective inhibitors is drawing attention for understanding of cellular redox homeostasis. Here, we describe the pharmacological properties of SPC-180002, which incorporates a methyl methacrylate group as a key pharmacophore, along with its comprehensive molecular mechanism as a novel dual inhibitor of SIRT1/3. The dual inhibition of SIRT1/3 by SPC-180002 disturbs redox homeostasis via ROS generation, which leads to an increase in both p21 protein stability and mitochondrial dysfunction. Increased p21 interacts with and inhibits CDK, thereby interfering with cell cycle progression. SPC-180002 leads to mitochondrial dysfunction by inhibiting mitophagy, which is accompanied by a reduction in oxygen consumption rate. Consequently, SPC-180002 strongly suppresses the proliferation of cancer cells and exerts anticancer effect in vivo. Taken together, the novel SIRT1/3 dual inhibitor, SPC-180002, impairs mitochondrial function and redox homeostasis, thereby strongly inhibiting cell cycle progression and cancer cell growth.
2023-11-01T00:00:00Z
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Extracellular Prdx1 mediates bacterial infection and inflammatory bone diseases
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/159479
Title: Extracellular Prdx1 mediates bacterial infection and inflammatory bone diseases
Authors: Kang, J.-H.; Lee, H.-Y.; Kim, N.-Y.; Lee, D.-S.; Yim, M.
Abstract: Aim: We aimed to determine the role of extracellular peroxiredoxin 1 (Prdx1) in the pathogenesis of bacterial infections and inflammatory bone disease. Materials and methods: We first investigated the role of Prdx1 using knockout mice. Next, we determined the role of extracellular Prdx1 in bacterial infections by using a neutralizing antibody against Prdx1. We finally investigated whether blockade of extracellular Prdx1 affected high- or low-grade inflammatory bone diseases using calvarial osteolysis, collagen-induced arthritis (CIA), and microgravity-induced bone loss in mouse models. Key findings: The lack of Prdx1 increased susceptibility to infections by Listeria monocytogenes or Escherichia coli. Prdx1 is released into the serum upon E. coli infection, and blockade of extracellular Prdx1 confers significant protection against bacterial infections. Our data suggested that circulating Prdx1 is increased by the development of osteolytic disease, and that blockade of extracellular Prdx1 exerts therapeutic effects against high- and low-grade inflammatory bone loss. In addition, the release of Prdx1 under inflammatory osteolytic conditions partly depends on non-canonical TIR-domain-containing adapter-inducing interferon-β (TRIF)-caspase-11-gasdemin D (GSDMD) inflammasome pathways. Significance: Extracellular Prdx1 is involved in the development of bacterial infections and inflammatory bone disease. Thus, extracellular Prdx1 may represent a novel therapeutic target for bacterial infections or inflammatory osteolytic diseases. © 2023 Elsevier Inc.
2023-11-01T00:00:00Z
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Ginsenoside Rg5 promotes muscle regeneration via p38MAPK and Akt/mTOR signaling
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/159498
Title: Ginsenoside Rg5 promotes muscle regeneration via p38MAPK and Akt/mTOR signaling
Authors: Kim Ryuni; Kim Jee Won; Choi Hyerim; Oh Ji-Eun; Kim Tae Hyun; Go Ga-Yeon; Lee Sang-Jin; Bae, Gyu Un
Abstract: Background: Skeletal muscles play a key role in physical activity and energy metabolism. The loss of skeletal muscle mass can cause problems related to metabolism and physical activity. Studies are being conducted to prevent such diseases by increasing the mass and regeneration capacity of muscles. Ginsenoside Rg5 has been reported to exhibit a broad range of pharmacological activities. However, studies on the effects of Rg5 on muscle differentiation and growth are scarce. Methods: To investigate the effects of Rg5 on myogenesis, C2C12 myoblasts were induced to differentiate with Rg5, followed by immunoblotting, immunostaining, and qRT-PCR for myogenic markers and promyogenic signaling (p38MAPK). Immunoprecipitation confirmed that Rg5 increased the interaction between MyoD and E2A via p38MAPK. To investigate the effects of Rg5 on prevention of muscle mass loss, C2C12 myotubes were treated with dexamethasone to induce muscle atrophy. Immunoblotting, immunostaining, and qRT-PCR were performed for myogenic markers, Akt/mTOR signaling for protein synthesis, and atrophy-related genes (Atrogin-1 and MuRF1). Results: Rg5 promoted C2C12 myoblast differentiation through phosphorylation of p38MAPK and MyoD/ E2A heterodimerization. Furthermore, Rg5 stimulated C2C12 myotube hypertrophy via phosphorylation of Akt/mTOR. Phosphorylation of Akt induces FoxO3a phosphorylation, which reduces the expression of Atrogin-1 and MuRF1. Conclusion: This study provides an understanding of how Rg5 promotes myogenesis and hypertrophy and prevents dexamethasone-induced muscle atrophy. The study is the first, to the best of our knowledge, to show that Rg5 promotes muscle regeneration and to suggest that Rg5 can be used for therapeutic intervention of muscle weakness and atrophy, including cancer cachexia. (c) 2023 The Korean Society of Ginseng. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
2023-11-01T00:00:00Z