• Title/Summary/Keyword: Small molecules

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Acceleration of Mesenchymal-to-Epithelial Transition (MET) during Direct Reprogramming Using Natural Compounds

  • Seo, Ji-Hye;Jang, Si Won;Jeon, Young-Joo;Eun, So Young;Hong, Yean Ju;Do, Jeong Tae;Chae, Jung-il;Choi, Hyun Woo
    • Journal of Microbiology and Biotechnology
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    • v.32 no.10
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    • pp.1245-1252
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    • 2022
  • Induced pluripotent stem cells (iPSCs) can be generated from somatic cells using Oct4, Sox2, Klf4, and c-Myc (OSKM). Small molecules can enhance reprogramming. Licochalcone D (LCD), a flavonoid compound present mainly in the roots of Glycyrrhiza inflata, acts on known signaling pathways involved in transcriptional activity and signal transduction, including the PGC1-α and MAPK families. In this study, we demonstrated that LCD improved reprogramming efficiency. LCD-treated iPSCs (LCD-iPSCs) expressed pluripotency-related genes Oct4, Sox2, Nanog, and Prdm14. Moreover, LCD-iPSCs differentiated into all three germ layers in vitro and formed chimeras. The mesenchymal-to-epithelial transition (MET) is critical for somatic cell reprogramming. We found that the expression levels of mesenchymal genes (Snail2 and Twist) decreased and those of epithelial genes (DSP, Cldn3, Crb3, and Ocln) dramatically increased in OR-MEF (OG2+/+/ROSA26+/+) cells treated with LCD for 3 days, indicating that MET effectively occurred in LCD-treated OR-MEF cells. Thus, LCD enhanced the generation of iPSCs from somatic cells by promoting MET at the early stages of reprogramming.

Searching for Novel Candidate Small Molecules for Ameliorating Idiopathic Pulmonary Fibrosis: a Narrative Review

  • Kyung-il Kim;Rajib Hossain;Xin Li;Hyun Jae Lee;Choong Jae Lee
    • Biomolecules & Therapeutics
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    • v.31 no.5
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    • pp.484-495
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    • 2023
  • Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)- β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

Recent Advances in the Chemobiological Upcycling of Polyethylene Terephthalate (PET) into Value-Added Chemicals

  • Joyce Mudondo;Hoe-Suk Lee;Yunhee Jeong;Tae Hee Kim;Seungmi Kim;Bong Hyun Sung;See-Hyoung Park;Kyungmoon Park;Hyun Gil Cha;Young Joo Yeon;Hee Taek Kim
    • Journal of Microbiology and Biotechnology
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    • v.33 no.1
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    • pp.1-14
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    • 2023
  • Polyethylene terephthalate (PET) is a plastic material commonly applied to beverage packaging used in everyday life. Owing to PET's versatility and ease of use, its consumption has continuously increased, resulting in considerable waste generation. Several physical and chemical recycling processes have been developed to address this problem. Recently, biological upcycling is being actively studied and has come to be regarded as a powerful technology for overcoming the economic issues associated with conventional recycling methods. For upcycling, PET should be degraded into small molecules, such as terephthalic acid and ethylene glycol, which are utilized as substrates for bioconversion, through various degradation processes, including gasification, pyrolysis, and chemical/biological depolymerization. Furthermore, biological upcycling methods have been applied to biosynthesize value-added chemicals, such as adipic acid, muconic acid, catechol, vanillin, and glycolic acid. In this review, we introduce and discuss various degradation methods that yield substrates for bioconversion and biological upcycling processes to produce value-added biochemicals. These technologies encourage a circular economy, which reduces the amount of waste released into the environment.

Evaluation of Radiological Effects on the Aptamers to Remove Ionic Radionuclides in the Liquid Radioactive Waste

  • Minhye Lee;Gilyong Cha;Dongki Kim;Miyong Yun;Daehyuk Jang;Sunyoung Lee;Song Hyun Kim;Hyuncheol Kim;Soonyoung Kim
    • Journal of Radiation Protection and Research
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    • v.48 no.1
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    • pp.44-51
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    • 2023
  • Background: Aptamers are currently being used in various fields including medical treatments due to their characteristics of selectively binding to specific molecules. Due to their special characteristics, the aptamers are expected to be used to remove radionuclides from a large amount of liquid radioactive waste generated during the decommissioning of nuclear power plants. The radiological effects on the aptamers should be evaluated to ensure their integrity for the application of a radionuclide removal technique. Materials and Methods: In this study, Monte Carlo N-Particle transport code version 6 (MCNP6) and Monte Carlo damage simulation (MCDS) codes were employed to evaluate the radiological effects on the aptamers. MCNP6 was used to evaluate the secondary electron spectrum and the absorbed dose in a medium. MCDS was used to calculate the DNA damage by using the secondary electron spectrum and the absorbed dose. Binding experiments were conducted to indirectly verify the results derived by MCNP6 and MCDS calculations. Results and Discussion: Damage yields of about 5.00×10-4 were calculated for 100 bp aptamer due to the radiation dose of 1 Gy. In experiments with radioactive materials, the results that the removal rate of the radioactive 60Co by the aptamer is the same with the non-radioactive 59Co prove the accuracy of the previous DNA damage calculation. Conclusion: The evaluation results suggest that only very small fraction of significant number of the aptamers will be damaged by the radioactive materials in the liquid radioactive waste.

Gut microbiota-generated metabolites: missing puzzles to hosts' health, diseases, and aging

  • Yan Zhang;Shibo Wei;Hang Zhang;Yunju Jo;Jong-Sun Kang;Ki-Tae Ha;Jongkil Joo;Hyun Joo Lee;Dongryeol Ryu
    • BMB Reports
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    • v.57 no.5
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    • pp.207-215
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    • 2024
  • The gut microbiota, an intricate community of bacteria residing in the gastrointestinal system, assumes a pivotal role in various physiological processes. Beyond its function in food breakdown and nutrient absorption, gut microbiota exerts a profound influence on immune and metabolic modulation by producing diverse gut microbiota-generated metabolites (GMGMs). These small molecules hold potential to impact host health via multiple pathways, which exhibit remarkable diversity, and have gained increasing attention in recent studies. Here, we elucidate the intricate implications and significant impacts of four specific metabolites, Urolithin A (UA), equol, Trimethylamine N-oxide (TMAO), and imidazole propionate, in shaping human health. Meanwhile, we also look into the advanced research on GMGMs, which demonstrate promising curative effects and hold great potential for further clinical therapies. Notably, the emergence of positive outcomes from clinical trials involving GMGMs, typified by UA, emphasizes their promising prospects in the pursuit of improved health and longevity. Collectively, the multifaceted impacts of GMGMs present intriguing avenues for future research and therapeutic interventions.

Chemical signalling within the rumen microbiome

  • Katie Lawther;Fernanda Godoy Santos;Linda B Oyama;Sharon A Huws
    • Animal Bioscience
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    • v.37 no.2_spc
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    • pp.337-345
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    • 2024
  • Ruminants possess a specialized four-compartment forestomach, consisting of the reticulum, rumen, omasum, and abomasum. The rumen, the primary fermentative chamber, harbours a dynamic ecosystem comprising bacteria, protozoa, fungi, archaea, and bacteriophages. These microorganisms engage in diverse ecological interactions within the rumen microbiome, primarily benefiting the host animal by deriving energy from plant material breakdown. These interactions encompass symbiosis, such as mutualism and commensalism, as well as parasitism, predation, and competition. These ecological interactions are dependent on many factors, including the production of diverse molecules, such as those involved in quorum sensing (QS). QS is a density-dependent signalling mechanism involving the release of autoinducer (AIs) compounds, when cell density increases AIs bind to receptors causing the altered expression of certain genes. These AIs are classified as mainly being N-acyl-homoserine lactones (AHL; commonly used by Gram-negative bacteria) or autoinducer-2 based systems (AI-2; used by Gram-positive and Gram-negative bacteria); although other less common AI systems exist. Most of our understanding of QS at a gene-level comes from pure culture in vitro studies using bacterial pathogens, with much being unknown on a commensal bacterial and ecosystem level, especially in the context of the rumen microbiome. A small number of studies have explored QS in the rumen using 'omic' technologies, revealing a prevalence of AI-2 QS systems among rumen bacteria. Nevertheless, the implications of these signalling systems on gene regulation, rumen ecology, and ruminant characteristics are largely uncharted territory. Metatranscriptome data tracking the colonization of perennial ryegrass by rumen microbes suggest that these chemicals may influence transitions in bacterial diversity during colonization. The likelihood of undiscovered chemicals within the rumen microbial arsenal is high, with the identified chemicals representing only the tip of the iceberg. A comprehensive grasp of rumen microbial chemical signalling is crucial for addressing the challenges of food security and climate targets.

Enhancing generation efficiency of liver organoids in a collagen scaffold using human chemically derived hepatic progenitors

  • Myounghoi Kim;Yohan Kim;Elsy Soraya Salas Silva;Michael Adisasmita;Kyeong Sik Kim;Yun Kyung Jung;Kyeong Geun Lee;Ji Hyun Shin;Dongho Choi
    • Annals of Hepato-Biliary-Pancreatic Surgery
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    • v.27 no.4
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    • pp.342-349
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    • 2023
  • Backgrounds/Aims: Liver organoids have emerged as a powerful tool for studying liver biology and disease and for developing new therapies and regenerative medicine approaches. For organoid culture, Matrigel, a type of extracellular matrix, is the most commonly used material. However, Matrigel cannot be used for clinical applications due to the presence of unknown proteins that can cause immune rejection, batch-to-batch variability, and angiogenesis. Methods: To obtain human primary hepatocytes (hPHs), we performed 2 steps collagenase liver perfusion protocol. We treated three small molecules cocktails (A83-01, CHIR99021, and HGF) for reprogramming the hPHs into human chemically derived hepatic progenitors (hCdHs) and used hCdHs to generate liver organoids. Results: In this study, we report the generation of liver organoids in a collagen scaffold using hCdHs. In comparison with adult liver (or primary hepatocyte)-derived organoids with collagen scaffold (hALO_C), hCdH-derived organoids in a collagen scaffold (hCdHO_C) showed a 10-fold increase in organoid generation efficiency with higher expression of liver- or liver progenitor-specific markers. Moreover, we demonstrated that hCdHO_C could differentiate into hepatic organoids (hCdHO_C_DM), indicating the potential of these organoids as a platform for drug screening. Conclusions: Overall, our study highlights the potential of hCdHO_C as a tool for liver research and presents a new approach for generating liver organoids using hCdHs with a collagen scaffold.

Inhibition of Class I Histone Deacetylase Enhances Self-Reprogramming of Spermatogonial Stem Cells into Pluripotent Stem Cells

  • Yukyeong Lee;Seung-Won Lee;Dahee Jeong;Hye Jeong Lee;Na Young Choi;Jin Seok Bang;Seokbeom Ham;Kinarm, Ko
    • International Journal of Stem Cells
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    • v.16 no.1
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    • pp.27-35
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    • 2023
  • Background and Objectives: Spermatogonial stem cells (SSCs) are the most primitive cells in spermatogenesis and are the only adult stem cells capable of passing on the genome of a given species to the next generation. SSCs are the only adult stem cells known to exhibit high Oct4 expression and can be induced to self-reprogram into pluripotent cells depending on culture conditions. Epigenetic modulation is well known to be involved in the induction of pluripotency of somatic cells. However, epigenetic modulation in self-reprogramming of SSCs into pluripotent cells has not been studied. Methods and Results: In this study, we examined the involvement of epigenetic modulation by assessing whether selfreprogramming of SSCs is enhanced by treatment with epigenetic modulators. We found that second-generation selective class I HDAC inhibitors increased SSC reprogramming efficiency, whereas non-selective HDAC inhibitors had no effect. Conclusions: We showed that pluripotent stem cells derived from adult SSCs by treatment with small molecules with epigenetic modulator functions exhibit pluripotency in vitro and in vivo. Our results suggest that the mechanism of SSC reprogramming by epigenetic modulator can be used for important applications in epigenetic reprogramming research.

Fire-Protective Coating for Polymer Construction Materials using Two-dimensional Nanomaterials (2차원 나노소재를 활용한 고분자 건축자재의 난연코팅기술 개발)

  • Kim, Hanim
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.44 no.2
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    • pp.183-190
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    • 2024
  • An environmentally-friendly nanocoating method that effectively adds flame retardant(FR) and gas shielding properties to combustible polymeric construction materials such as flexible polyurethane (PU) foam was studied. Naturally-driven two-dimensional(2D) nanomaterials such as graphene oxide (GO) can exhibit liquid crystalline (LC) properties in aqueous solutions, enabling uniform coatings on the various substrates including 3D-porous foams. LC phase-assisted coating serves as 3D-scaffold, facilitating the introduction of small molecules having antioxidant capabilities such as dopamine which is to form uniformly stacked FR coating. Additionally, the structural characteristics of the 2D-materials can effectively hinder the migration of toxic gases and flammable substances in the gas phase generated during combustion. This LC phase flame retardant coating technology could be a new approach to provide environmentally friendly and effective flame retardant and gas barrier properties to various types of polymeric materials.

Investigation on Formation Behaviors of Synthesized Natural Gas Hydrates (합성 천연가스의 하이드레이트 형성 거동 연구)

  • Lee, Jong-Won;Lee, Ju-Dong
    • Korean Chemical Engineering Research
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    • v.50 no.5
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    • pp.890-893
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    • 2012
  • Gas hydrates are solid crystal structures formed by enclathration of gaseous guest species into 3-dimensional lattice structure of hydrogen-bonded water molecules. These compounds can be potentially used as an energy storage/transportation medium because they can hold a large amount of gas in a small volume of the solid phase. In addition, huge amount of natural gas, buried in seabeds or permafrost region in the form of the solid hydrate, is regarded as a future energy source. In this study, synthesized natural gas, whose composition is 90.0 mol% of methane, 7.0 mol% of ethane, and 3.0 mol% of propane, was used to identify formation behaviors of natural gas hydrates for the purpose of applying the gas hydrate to a storage/transportation medium of natural gas. According to the experimental results obtained by means of the solid-state NMR and high-resolution powder XRD methods, it is found that formed natural gas hydrates have crystal structure of the structure-II hydrate, and that methane occupies both small and large cages, while the others only occupy large ones. In addition, both the NMR spectroscopy and the gas chromatograph showed that there exists preferential occupation among the natural gas components during the hydrate formation. Compositional changes after the hydrate formation revealed that the preferential occupation is in order of propane, ethane, and methane (propane is the most preferential guest species when forming natural gas hydrates).