Publications by authors named "Ohman Kwon"

Article Synopsis
  • - The study addresses the limitations of using undefined basement membrane extracts like Matrigel for cultivating intestinal stem cells (ISCs) by introducing a new xenogeneic-free culture dish called XF-DISC.
  • - XF-DISC significantly increases the growth and maintenance of ISCs, achieving a 24-fold cell number increase within 30 days and sustaining viability over 210 days (30 passages).
  • - This method allows for successful transplantation of cultured human ISCs into mouse models with intestinal injuries, fostering tissue regeneration, making it a promising approach for effective ISC therapy in human intestinal diseases.
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  • The study focuses on VacA, a toxin from Helicobacter pylori, investigating its harmful effects on specific types of stomach cells, particularly how it damages mitochondria and affects cell function.
  • Researchers used human gastric organoids (hAGOs) and tissue samples from infected patients to demonstrate that VacA leads to significant mitochondrial damage and reduced energy production, which weakens the stomach's protective barrier.
  • The study identified a potential treatment, MLN8054, that can repair VacA-induced mitochondrial damage and restore the integrity of gastric cells, highlighting hAGOs as an effective model for testing new drugs against VacA-related diseases.
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Human pluripotent stem cells (hPSCs), encompassing human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold immense potential in regenerative medicine, offering new opportunities for personalized cell therapies. However, their clinical translation is hindered by the inevitable reliance on xenogeneic components in culture environments. This study addresses this challenge by engineering a fully synthetic, xeno-free culture substrate, whose surface composition is tailored systematically for xeno-free culture of hPSCs.

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  • Scientists created a special way to grow tiny human intestinal organs (called organoids) for research, making sure they grow well and are easy to use.
  • They used special human stem cells that can turn into different types of intestinal cells, helping researchers understand how intestines work and stay healthy.
  • This new method also helps scientists study diseases, like how a virus affects the intestines, and could be useful for future medicines and treatments.
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Little is known about the modulatory capacity of the microbiota in early intestinal development. We examined various intestinal models that respond to gut microbial metabolites based on human pluripotent stem cell-derived human intestinal organoids (hIOs): physiologically relevant fetal-like intestine, intestinal stem cell, and intestinal disease models. We found that a newly isolated strain DS0384 accelerated maturation of the fetal intestine using 3D hIO with immature fetal characteristics.

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Many of early findings regarding intestinal stem cells (ISCs) and their niche in the human intestine have relied on colorectal cancer cell lines and labor-intensive and time-consuming mouse models. However, these models cannot accurately recapitulate the physiologically relevant aspects of human ISCs. In this study, we demonstrate a reliable and robust culture method for 3D expanding intestinal spheroids (InS) mainly comprising ISCs and progenitors, which can be derived from 3D human intestinal organoids (HIOs).

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The gastrointestinal tract is the most common exposure route of xenobiotics, and intestinal toxicity can result in systemic toxicity in most cases. It is important to develop intestinal toxicity assays mimicking the human system; thus, stem cells are rapidly being developed as new paradigms of toxicity assessment. In this study, we established human embryonic stem cell (hESC)-derived enterocyte-like cells (ELCs) and compared them to existing and models.

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Human pluripotent stem cell (hPSC)-derived intestinal organoids (HIOs) hold unprecedented promise for basic biology and translational applications. However, developing a quantitative method to evaluate the epithelial cell membrane integrity of HIOs as an intestinal barrier model is a major challenge because of their complex three-dimensional (3D) structure. In this study, we developed an impedance system to measure the change in electrical resistance of 3D HIOs depending on the integrity of the intestinal epithelial cell membrane, which can reflect functionality and maturity.

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Advanced technologies are required for generating human intestinal epithelial cells (hIECs) harboring cellular diversity and functionalities to predict oral drug absorption in humans and study normal intestinal epithelial physiology. We developed a reproducible two-step protocol to induce human pluripotent stem cells to differentiate into highly expandable hIEC progenitors and a functional hIEC monolayer exhibiting intestinal molecular features, cell type diversity, and high activities of intestinal transporters and metabolic enzymes such as cytochrome P450 3A4 (CYP3A4). Functional hIECs are more suitable for predicting compounds metabolized by CYP3A4 and absorbed in the intestine than Caco-2 cells.

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The morphology and structure of the intestinal epithelium are rearranged dynamically during development, tissue regeneration, and disease progression. The most important characteristic of intestinal epithelial morphogenesis is the repetitive compartmentalized structures of crypt-villus units, which are crucial for maintaining intestinal homeostasis and functions. Abnormal structures are known to be closely associated with disease development and progression.

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Article Synopsis
  • * In the study, mice with DSS-induced colitis received low-dose IL-2, showing significant improvements in survival, weight, and reduction of inflammation, particularly at doses of 16K-32K IU/day.
  • * The treatment not only restored colonic barrier integrity but also regulated gene expressions similar to those in healthy controls, highlighting the importance of the PI3K-AKT pathway in IL-2's therapeutic effects for
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Human intestinal organoids (hIOs), which resemble the human intestine structurally and physiologically, have emerged as a new modality for the study of the molecular and cellular biology of the intestine in vitro. We recently developed an in vitro maturation technique for generating functional hIOs from human pluripotent stem cells (hPSCs). Here, we investigated the function of STAT3 for inducing in vitro maturation of hIOs.

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Short‑chain fatty acids (SCFAs; butyrate, propionate and acetate) are metabolites derived from the gut microbiota via dietary fiber fermentation. In colon cancer, treatment with SCFAs, mainly butyrate and propionate, suppresses cell proliferation, migration and invasion. Furthermore, although sodium butyrate is known to induce cell apoptosis in lung cancer, the anticancer effects of sodium propionate (SP) on lung cancer are not well understood.

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Spinal muscular atrophy (SMA) is caused by the mutation or deletion of the survival motor neuron 1 (SMN1) gene. Only ∼10% of the products of SMN2, a paralogue of SMN1, are functional full-length SMN (SMN-FL) proteins, whereas SMN2 primarily produces alternatively spliced transcripts lacking exon 7. Reduced SMN protein levels in SMA patients lead to progressive degeneration of spinal motor neurons (MNs).

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Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism of maturation remaining elusive. Here, we show that the co-culture with human T lymphocytes induce the in vitro maturation of hIOs, and identify STAT3-activating interleukin-2 (IL-2) as the major factor inducing maturation.

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Article Synopsis
  • The localization of mTORC1 to lysosomes is essential for its activation, and this process relies on Rag GTPases.
  • NUDT2 is identified as a new positive regulator of mTORC1 activation, as its silencing leads to impaired mTORC1 activation.
  • NUDT2 interacts with Rag GTPases and is necessary for the translocation of mTORC1 to lysosomal membranes, which is vital for the proliferation of breast cancer cells.
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Resveratrol (RSV) is a natural polyphenol that has a beneficial effect on health, and resveratrol-induced autophagy has been suggested to be a key process in mediating many beneficial effects of resveratrol, such as reduction of inflammation and induction of cancer cell death. Although various resveratrol targets have been suggested, the molecule that mediates resveratrol-induced autophagy remains unknown. Here, we demonstrate that resveratrol induces autophagy by directly inhibiting the mTOR-ULK1 pathway.

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Mast cells are responsible for IgE-mediated allergic responses through the secretion of various inflammatory cytokines and mediators. Therefore, the pharmacological regulation of mast cell activation is an important goal in the development of novel anti-allergic drugs. In this study, we found that spiraeoside (SP) inhibits mast cell activation and allergic responses in vivo.

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Phospholipase C-β (PLC-β) is a key molecule in G protein-coupled receptor (GPCR)-mediated signaling. Many studies have shown that the four PLC-β subtypes have different physiological functions despite their similar structures. Because the PLC-β subtypes possess different PDZ-binding motifs, they have the potential to interact with different PDZ proteins.

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Phospholipase C-η1 (PLC-η1) is the most recently identified PLC isotype and is primarily expressed in nerve tissue. However, its functional role is unclear. In the present study, we report for the first time that PLC-η1 acts as a signal amplifier in G protein-coupled receptor (GPCR)-mediated PLC and Ca(2+) signaling.

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