• BMB Reports
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• v.51 no.5
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• pp.209-210
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• 2018

NAFLD induces the development of advanced liver diseases such as NASH and liver cancer. Therefore, understanding the mechanism of NAFLD development is critical for its prevention and treatment. Ablation of PTEN or Hippo pathway components induces liver cancer in a murine model by hyperactive AKT or YAP/TAZ, respectively. Although the regulation of these two pathways occurs in the same hepatocyte, the details of crosstalk between Hippo-YAP/TAZ and PTEN-AKT pathways in liver homeostasis and tumorigenesis still remain unclear. Here, we found that depletion of both PTEN and SAV1 in liver promotes spontaneous NAFLD and liver cancer through hyperactive AKT via YAP/TAZ-mediated up-regulation of IRS2 transcription. Conversely, NAFLD is rescued by both ablation of YAP/TAZ and activation of the Hippo pathway. Furthermore, human HCC patients with NAFLD showed strong correlation between YAP/TAZ and IRS2 or phospho-AKT expression. Finally, the inhibition of AKT by MK-2206 treatment attenuates NAFLD development and tumorigenesis. Our findings indicate that Hippo pathway interacts with AKT signaling during the intervention with IRS2 to prevent NAFLD and liver cancer.

• Genomics & Informatics
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• v.21 no.1
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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.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.555-564
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• 2021

We investigated the effects of naringenin and morin on IL-5 and ROS production in PMA+ionomycin-treated EL-4 cells with the corroboration of their antioxidant and anti-inflammatory properties using an asthma-induced mouse model. The EL-4 cell line was used to study the outcomes of naringenin or morin, followed by cell viability studies. Western blot analysis and ELISA test were used to determine Th2 mediated cytokines. In vivo studies were carried out on BALB/c mice to induce allergic asthma using ovalbumin administered intraperitoneally. Intracellular ROS was determined using 2',7'-dichlorodihydrofluorescein diacetate, followed by serum enzymatic (AST and ALT) estimations and inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and lung tissues. Histopathological studies were conducted to examine lung tissue-stained architecture. Our findings suggested that naringenin and morin significantly suppressed IL-5 and ROS production via various pathways. Interestingly, by reducing NFAT activity, naringenin and morin stimulated HO-1 expression, thereby suppressing IL-5 secretion due to regulating the transcription factor Nrf2 via P13/Akt or ERK/JNK signalling pathways in EL-4 cells, demonstrating the involvement of HO-1 expression in inhibiting asthmatic inflammation. The increased inflammatory cells in the BALF were substantially decreased by both naringenin and morin, followed by inhibition in the elevated Th-2 cytokines levels. The TNF-α protein levels in an allergic asthma mouse model were significantly reduced by suppressing Akt phosphorylation and eosinophil formation. Recent findings confirmed that naringenin and morin possess the potential to control asthma-related immune responses through antioxidant and anti-inflammatory properties, indicating potential therapeutic agents or functional foods.

• The Journal of Pediatrics of Korean Medicine
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• v.36 no.1
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• pp.65-77
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• 2022

Objectives The purpose of this study was to understand the public's perception of Korean medical treatment for growth disorders to develop Korean medicine clinical practice guidelines and critical pathways for growth disorders in children and adolescents. Methods A survey was conducted using an online platform targeting 252 adults aged 19 years from May 16, 2021 to May 17, 2021. The questionnaire consisted of questions about the demographic characteristics of respondents; overall perception, experience, and satisfaction with Korean medical treatment for growth disorders; willingness to use or recommend Korean medical treatment for growth disorders; and points for improvement. Results The overall perception of treatment for growth disorders was 3.30 ± 0.892 on a 5-point scale. Concerning the negative reasons, 54.4% of the respondents were concerned about safety; regarding the positive reason, expectations for overall health as well as height growth were the highest at 46.5%. Additionally, there was a high demand for information, such as providing safety information on treatment, presenting evidence for the efficacy of treatment, and standardized clinical process, as points requiring improvement. Conclusions To raise public perception of Korean medical treatment for growth disorders, it is necessary to satisfy the opinions of the public identified through this survey. Therefore, the development and utilization of Korean medicine clinical practice guidelines and critical pathways for growth disorders would play an important role.

• Quality Improvement in Health Care
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• v.28 no.1
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• pp.2-13
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• 2022

Purpose: This study assessed the status of the Development and Utilization of critical pathways (CP) in South Korea. Methods: We surveyed 195 hospitals obtained on the Korean Hospital Association website. Data were collected using structured questionnaires for staff members in charge of CP management personnel in these hospitals. The questionnaire included CP developed by the institutions, the coverage rates and completion rates of CP in the current year, and management indicators related to CP. The questionnaire also included CP support systems and content within the institutions and questions regarding the advantages of CP utilization and obstacles associated with the CP development process. Results: Analysis of the responses from 70 hospitals (35.9% response rate) showed that a total of 1,370 CP sets were developed. The number of CP related to surgery departments was 365 (26.6%), and CP related to surgery and procedure was 1,093 (79.8%), respectively. The CP coverage rate was the most frequently used indicator to monitor the effect of CP (97.1%), followed by the completion rate (90.0%) and the length of stay in hospital (61.4%). CP managers reported that CP were highly useful for communication (3.39±0.493) and accurate information provision (3.39±0.491). The perception that CP violated doctors' autonomy in treatment was relatively low (2.87±0.645). Conclusion: It is necessary to establish an infrastructure in hospitals for CP. CP can facilitate communication and provide accurate information.

• The Plant Pathology Journal
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• v.26 no.1
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• pp.1-7
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• 2010

Phosphorylation is a major post-translational modification of proteins that regulate diverse signal transduction pathways in eukaryotic cells. 14-3-3 proteins are regulatory proteins that bind to target proteins in a phosphorylation-dependent manner and have been shown to play an important role in plant growth and development, primary metabolism, and signal transduction. Because phosphorylation plays a critical role in signal transduction pathways to trigger plant immunity, involvement of 14-3-3 proteins in plant immunity has been suggested for a long time. Recent studies have provided new evidence to support a role for 14-3-3 proteins in plant immunity. This review will briefly discuss general characteristics of 14-3-3 proteins and their involvement in plant immunity.

• Biomedical Science Letters
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• v.23 no.4
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• pp.295-302
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• 2017

Mononuclear osteoclast precursors derived from hematopoietic progenitors fuse together and then become multinucleated mature osteoclasts by macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL). Especially, the binding of RANKL to its receptor RANK provides key signals for osteoclast differentiation and bone-resorbing function. RANK transduces intracellular signals by recruiting adaptor molecules such as TNFR-associated factors (TRAFs), which then activate mitogen activated protein kinases (MAPKs), Src/PI3K/Akt pathway, nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and finally amplify NFATc1 activation for the transcription and activation of osteoclast marker genes. This review will briefly describe RANKL-RANK signaling pathways and key molecules critical for osteoclast differentiation.

• BMB Reports
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• v.41 no.4
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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.

• Molecules and Cells
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• v.42 no.12
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• pp.828-835
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• 2019

PIWI Argonaute proteins and Piwi-interacting RNAs (piRNAs) are expressed in all animal species and play a critical role in cellular defense by inhibiting the activation of transposable elements in the germline. Recently, new evidence suggests that PIWI proteins and piRNAs also play important roles in various somatic tissues, including neurons. This review summarizes the neuronal functions of the PIWI-piRNA pathway in multiple animal species, including their involvement in axon regeneration, behavior, memory formation, and transgenerational epigenetic inheritance of adaptive memory. This review also discusses the consequences of dysregulation of neuronal PIWI-piRNA pathways in certain neurological disorders, including neurodevelopmental and neurodegenerative diseases. A full understanding of neuronal PIWI-piRNA pathways will ultimately provide novel insights into small RNA biology and could potentially provide precise targets for therapeutic applications.

• Molecules and Cells
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• v.41 no.8
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• pp.705-716
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• 2018

The endoplasmic reticulum (ER) is a critical organelle for protein synthesis, folding and modification, and lipid synthesis and calcium storage. Dysregulation of ER functions leads to the accumulation of misfolded- or unfolded-protein in the ER lumen, and this triggers the unfolded protein response (UPR), which restores ER homeostasis. The UPR is characterized by three distinct downstream signaling pathways that promote cell survival or apoptosis depending on the stressor, the intensity and duration of ER stress, and the cell type. Mammalian cells express the UPR transducers IRE1, PERK, and ATF6, which control transcriptional and translational responses to ER stress. Direct links between ER stress and immune responses are also evident, but the mechanisms by which UPR signaling cascades are coordinated with immunity remain unclear. This review discusses recent investigations of the roles of ER stress in immune responses that lead to differentiation, maturation, and cytokine expression in immune cells. Further understanding of how ER stress contributes to the pathogenesis of immune disorders will facilitate the development of novel therapies that target UPR pathways.