Biology subjects

Jeong, D.

Publications and source records attributed to Jeong, D..

22 records · Page 2Linked to original sources

bioRxiv2020

Establishing a Living Biobank of Patient-Derived Organoids of Intraductal Papillary Mucinous Neoplasms of the Pancreas

Pancreatic cancer (PaCa) is the third leading cause of cancer-related deaths in the United States. There is an unmet need to develop strategies to detect PaCa at an early, operable stage and prevent its progression. Intraductal papillary mucinous neoplasms (IPMNs) are cystic PaCa precursors that comprise nearly 50% of pancreatic cysts detected incidentally via cross-sectional imaging. Since IPMNs can progress from low- and moderate-grade dysplasia to high-grade dysplasia and invasion, the study of these lesions offers a prime opportunity to develop early detection and prevention strategies. Organoids are an ideal preclinical platform to study IPMNs, and the objective of the current investigation was to establish a living biobank of patient-derived organoids (PDO) from IPMNs. IPMN tumors and adjacent normal pancreatic tissues were successfully harvested from 15 patients with IPMNs undergoing pancreatic surgical resection at Moffitt Cancer Center & Research Institute (Tampa, FL) between May of 2017 and March of 2019. Organoid cultures were also generated from cryopreserved tissues. Organoid count and size were determined over time by both Image-Pro Premier 3D Version 9.1 digital platform and Matlab application of a Circular Hough Transform algorithm, and histologic and genomic characterization of a subset of the organoids was performed using immunohistochemistry and targeted sequencing, respectively. The success rates for organoid generation from IPMN tumor and adjacent normal pancreatic tissues were 81% and 87%, respectively. IPMN organoids derived from different epithelial subtypes showed different morphologies in vitro, and organoids recapitulated histologic and genomic characteristics of the parental IPMN tumor. In summary, this pre-clinical model has the potential to provide new opportunities to unveil mechanisms of IPMN progression to invasion and to shed insight into novel biomarkers for early detection and targets for chemoprevention.

cancer biology↗

bioRxiv2019

MyD88-Syk axis is a critical determinant for inflammatory response in macrophages

Inhibition of Syk or MyD88 decreased generation of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and consequent ROS/RNS-induced phagocytic activity in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Syk inhibition downregulated expression of ROS/RNS-generating enzymes by inhibiting the nuclear factor-kappa B (NF-kappa?B) signaling pathway and phagocytic activity by suppressing suppressor of cytokine signaling 1 (SOCS1) via its nitration in the LPS-stimulated RAW264.7 cells. Inhibition of ROS/RNS generation suppressed SOCS1 nitration, leading to a decrease in the phagocytic activity. Syk was activated by the interaction with MyD88, and the tyrosine 58 residue (Y58) in the hemi-immunoreceptor tyrosine-based activation motif (ITAM) of MyD88 was critical for interaction and consequent activation of Syk in macrophages. Src activated MyD88 by phosphorylation at Y58 via the Src kinase domain. Moreover, LPS-induced formation of filamentous actin (F-actin) and Ras-related C3 botulinum toxin substrate 1 (Rac1) activation induced Src activation. Conclusivley, these results suggest that the MyD88-Syk axis plays a pivotal role in macrophage-mediated inflammatory responses by inducing ROS/RNS generation and phagocytic activity via activation of Src and its upstream stimulators, F-actin and Rac1.

immunology↗

bioRxiv2018

Concentration-dependent reduction of planktonic- and biofilm-state Vibrio alginolyticus by the bacteriophage pVa-21

There is an increasing emergence of antibiotic-resistant Vibrio alginolyticus, a zoonotic pathogen that causes mass mortality in aquatic animals as well as human infection; therefore, there is a demand for alternatives to antibiotics for treatment and prevention of infections caused by this pathogen. One possibility is through the exploitation of bacteriophages. In the present study, the bacteriophage pVa-21 belonging to Myoviridae, was isolated and characterized as a candidate biocontrol agent against V. alginolyticus. Its morphology, host range and infectivity, growth characteristics, planktonic or biofilm lytic property, stability under various conditions, and genome were investigated. Its latent period and burst size were estimated to be approximately 70 min and 58 plaque-forming units/cell, respectively. In addition, phage pVa-21 could inhibit bacterial growth both in the planktonic and biofilm state. Furthermore, phylogenetic and genome analyses revealed that the phage is closely related to phiKZ-like phages and can be classified as a new member of the phiKZ-like phages that infect bacteria belonging to the family Vibrionaceae.

microbiology↗

bioRxiv2018

Gradual repression of selenoprotein W ensures physiological bone remodelling

Selenoproteins containing selenium in the form of selenocysteine are critical for bone remodelling. However, their mechanism of action is not well understood. Here, we report the identification of selenoprotein W (SELENOW) through large-scale mRNA profiling of receptor activator of nuclear factor (NF)-{kappa}B ligand (RANKL)-induced osteoclast differentiation, as a protein that is downregulated via RANKL/RANK/tumour necrosis factor receptor-associated factor 6/p38 signalling. RNA sequencing analysis revealed that SELENOW regulates osteoclastogenic genes. SELENOW overexpression enhanced osteoclastogenesis in vitro via nuclear translocation of NF-{kappa}B and nuclear factor of activated T-cells cytoplasmic 1, whereas its loss suppressed osteoclast formation. SELENOW-deficient and SELENOW-overexpressing mice exhibited osteopetrosis and osteoporosis, respectively. Ectopic SELENOW expression stimulated cell-cell fusion critical for osteoclast maturation as well as bone resorption. Thus, RANKL-dependent repression of SELENOW maintains proper osteoclast differentiation and blocks osteoporosis caused by overactive osteoclasts. These findings demonstrate a biological link between selenium and bone metabolism.

physiology↗