• Genomics & Informatics
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• 제21권1호
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• pp.6.1-6.8
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• 2023

Glaucoma is the second leading cause of irreversible blindness, and primary open-angle glaucoma (POAG) is the most common type. Due to inadequate diagnosis, treatment is often not administered until symptoms occur. Hence, approaches enabling earlier prediction or diagnosis of POAG are necessary. We aimed to identify novel drugs for glaucoma through bioinformatics and network analysis. Data from 36 samples, obtained from the trabecular meshwork of healthy individuals and patients with POAG, were acquired from a dataset. Next, differentially expressed genes (DEGs) were identified to construct a protein-protein interaction (PPI) network. In both stages, the genes were enriched by studying the critical biological processes and pathways related to POAG. Finally, a drug-gene network was constructed, and novel drugs for POAG treatment were proposed. Genes with p < 0.01 and |log fold change| > 0.3 (1,350 genes) were considered DEGs and utilized to construct a PPI network. Enrichment analysis yielded several key pathways that were upregulated or downregulated. For example, extracellular matrix organization, the immune system, neutrophil degranulation, and cytokine signaling were upregulated among immune pathways, while signal transduction, the immune system, extracellular matrix organization, and receptor tyrosine kinase signaling were downregulated. Finally, novel drugs including metformin hydrochloride, ixazomib citrate, and cisplatin warrant further analysis of their potential roles in POAG treatment. The candidate drugs identified in this computational analysis require in vitro and in vivo validation to confirm their effectiveness in POAG treatment. This may pave the way for understanding life-threatening disorders such as cancer.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2021년도 춘계학술대회
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• pp.56-56
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• 2021

Nypa fruticans Wurmb is a mangrove plant belonging to Araceae family. N. fruticans is typically found in Southeast Asia, and in some parts of Queensland, Australia. N. fruticans has phytochemicals, phenolics, and flavonoids. In this study, we investigated the anti-inflammatory effects of the ethyl acetate fraction of N. fruticans (ENF) on the production and expression of cytokines and inflammatory mediators through the major signal transduction pathways. ENF attenuated the level of cytokines in a dose-dependent manner and decreased the production of nitric oxide (NO). ENF decreased the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) via alleviating transcription of nuclear factor-kappa B (NF-κB) by an inhibitor of nuclear factor-kappa B (IκB) degradation. Furthermore, mitogen-activated protein kinase (MAPK) signaling pathways (ERK1/2, JNK1/2, and p38) are known to be involved in the inflammatory response. Phosphorylations of ERK1/2, JNK1/2, and p38 were significantly decreased compared with the ENF-untreated control. Conclusively, ENF was related to alleviating various pro-inflammatory mediators through IκB/NF-κB and MAPK signaling pathways, including p65 translocation to the nucleus.

• BMB Reports
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• 제41권4호
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• pp.267-277
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• 2008

Insects mount a robust innate immune response against a wide array of microbial pathogens. The hallmark of the Drosophila humoral immune response is the rapid production of anti-microbial peptides in the fat body and their release into the circulation. Two recognition and signaling cascades regulate expression of these antimicrobial peptide genes. The Toll pathway is activated by fungal and many Gram-positive bacterial infections, whereas the immune deficiency (IMD) pathway responds to Gram-negative bacteria. Recent work has shown that the intensity and duration of the Drosophila immune response is tightly regulated. As in mammals, hyperactivated immune responses are detrimental, and the proper down-modulation of immunity is critical for protective immunity and health. In order to keep the immune response properly modulated, the Toll and IMD pathways are controlled at multiple levels by a series of negative regulators. In this review, we focus on recent advances identifying and characterizing the negative regulators of these pathways.

• Mass Spectrometry Letters
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• 제7권4호
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• pp.85-90
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• 2016

Post-translational modifications (PTMs) of proteins regulate self-renewal and differentiation in embryonic stem cells (ESCs). Nitration of tyrosine residues of proteins in ESCs modulates their downstream pathways, which can affect self-renewal and differentiation. However, protein tyrosine nitration (PTN) in ESCs has been rarely studied. We reviewed 23 nitrated sites in stem cell proteins. Functional enrichment analysis showed that these nitrated proteins are involved in signal transduction, cell adhesion and migration, and cell proliferation in ESCs. Comparison between the nitrated and known phosphorylated sites revealed that 7 nitrated sites had overlapping phosphorylated sites, indicating functional links of PTNs to their associated signaling pathways in ESCs. Therefore, nitrated proteome provides a basis for understanding potential roles of PTN in self-renewal and differentiation of ESCs.

• BMB Reports
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• 제44권5호
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• pp.291-297
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• 2011

Aging is one of the most complicated biological processes in all species. A number of different model organisms from yeast to monkeys have been studied to understand the aging process. Until recently, many different age-related genes and age-regulating cellular pathways, such as insulin/IGF-1-like signal, mitochondrial dysfunction, Sir2 pathway, have been identified through classical genetic studies. Parallel to genetic approaches, genome-wide approaches have provided valuable insights for the understanding of molecular mechanisms occurring during aging. Gene expression profiling analysis can measure the transcriptional alteration of multiple genes in a genome simultaneously and is widely used to elucidate the mechanisms of complex biological pathways. Here, current global gene expression profiling studies on normal aging and age-related genetic/environmental interventions in widely-used model organisms are briefly reviewed.

• BMB Reports
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• 제41권2호
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• pp.93-101
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• 2008

The major cell wall components of bacteria are lipopolysaccharide, peptidoglycan, and teichoic acid. These molecules are known to trigger strong innate immune responses in the host. The molecular mechanisms by which the host recognizes the peptidoglycan of Gram-positive bacteria and amplifies this peptidoglycan recognition signals to mount an immune response remain largely unclear. Recent, elegant genetic and biochemical studies are revealing details of the molecular recognition mechanism and the signalling pathways triggered by bacterial peptidoglycan. Here we review recent progress in elucidating the molecular details of peptidoglycan recognition and its signalling pathways in insects. We also attempt to evaluate the importance of this issue for understanding innate immunity.

• 대한이식학회지
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• 제28권3호
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• pp.113-120
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• 2014

Two-signal models are useful in explaining various types of immune responses. In particular, secondary, so-called costimulatory, signals are critically required for the process of T-cell activation, survival, differentiation, and memory formation. Early studies in rodent models showed that targeting T-cell costimulatory pathways elicits immunological tolerance, providing a basis for development of costimulatory therapeutics in allograft rejection. However, as the classic definition of T-cell costimulation continues to evolve, simple blockade of costimulatory pathways has limitations in prevention of allograft rejection. Furthermore, functions of costimulatory molecules are much more diverse than initially anticipated and beyond T cells. In this mini-review, we will discuss CD137-CD137L bidirectional signals as examples showing that two-signals can be applicable to multiple phases of immune responses.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2002년도 추계학술대회
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• pp.203-205
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• 2002

Light is an environmental signal that regulates photomovement and main energy source of photosynthesis in the cyanobacterium Synechocystis sp. PCC 6803 (Syn6803). Syn6803 is a popular model system for study of plant functional genomics. In this report, we adopted 2D gel based proteomics study to investigate proteins related with the light absorption and photo-protection in Syn6803. More than 700 proteins were detected on the SDS-gels stained with silver nitrate. Several proteins showing different expression level under various light conditions were identified with MALDI-TOF Mass spectrometry. As a comparison, we also conducted ICAT-based proteome study using WT and cphl (cyanobacterial phytochrome 1) mutant. A cphl deletion led to changes in the expression of proteins involved in translation, photosynthesis including photosystem and CO2 fixation, and cellular regulation. We are currently involved in TAP-tagging method to study protein-protein interactions in search for the molecular component involved in the light signal transduction of Syn6803 photomovement.

• BMB Reports
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• 제47권12호
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• pp.655-659
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• 2014

Integrin-mediated cell adhesion is important for development, immune responses, hemostasis and wound healing. Integrins also function as signal transducing receptors that can control intracellular pathways that regulate cell survival, proliferation, and cell fate. Conversely, cells can modulate the affinity of integrins for their ligands a process operationally defined as integrin activation. Analysis of activation of integrins has now provided a detailed molecular understanding of this unique form of "inside-out" signal transduction and revealed new paradigms of how transmembrane domains (TMD) can transmit long range allosteric changes in transmembrane proteins. Here, we will review how talin and mediates integrin activation and how the integrin TMD can transmit these inside out signals.

• Tuberculosis and Respiratory Diseases
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• 제43권2호
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• pp.123-127
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• 1996

Secretion of surfactant phospholipid can be stimulated by a variety of agonists acting via at least three different signal transduction mechanisms. These include the adenylate cyclase system with activation of cAMP-dependent protein kinase; activation of protein kinase C either directly or subsequent to activation of phosphoinositide-specific phospholipase C and generation of diacylglycerols and inositol trisphosphate; and a third mechanism that involves incresed $Ca^{2+}$ levels and a calmodulin-dependent step. ATP stimulates secretion via all three mechanisms. The protein kinase C pathway is also coupled to phopholipase D which, acting on relatively abundant cellular phospholipids, generates diacylglycerols that further activate protein kinase C. Sustained protein kinase C activation can maintain phosphatidylcholine secretion for a prolonged period of time. It is likely that interactions between the different signaling pathways have an important role in the overall physiological regulation of surfactant secretion.