• Journal of Microbiology and Biotechnology
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• v.32 no.1
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• pp.126-140
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• 2022

Stem cells can be applied usefully in basic research and clinical field due to their differentiation and self-renewal capacity. The aim of this study was to establish an effective novel therapeutic cellular source and create its molecular expression profile map to elucidate the possible therapeutic mechanism and signaling pathway. We successfully obtained a mesenchymal stem cell population from human embryonic stem cells (hESCs) cultured on chemically defined feeder-free conditions and treated with connective tissue growth factor (CTGF) and performed the expressive proteomic approach to elucidate the molecular basis. We further selected 12 differentially expressed proteins in CTGF-induced hESC-derived mesenchymal stem cells (C-hESC-MSCs), which were found to be involved in the metabolic process, immune response, cell signaling, and cell proliferation, as compared to bone marrow derived-MSCs(BM-MSCs). Moreover, these up-regulated proteins were potentially related to the Wnt/β-catenin pathway. These results suggest that C-hESC-MSCs are a highly proliferative cell population, which can interact with the Wnt/β-catenin signaling pathway; thus, due to the upregulated cell survival ability or downregulated apoptosis effects of C-hESC-MSCs, these can be used as an unlimited cellular source in the cell therapy field for a higher therapeutic potential. Overall, the study provided valuable insights into the molecular functioning of hESC derivatives as a valuable cellular source.

• Journal of Microbiology and Biotechnology
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• v.32 no.2
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• pp.205-211
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• 2022

Probiotics can effectively modulate host immune responses and prevent gastrointestinal diseases. The objective of this study was to investigate the probiotic characteristics of Lactobacillus brevis KU15152 isolated from kimchi and its protective potential against intestinal inflammation induced by Staphylococcus aureus lipoteichoic acid (aLTA). L. brevis KU15152 exhibited a high survival rate in artificial gastric and bile environments. Additionally, the adhesion capability of the strain to HT-29 cells was higher than that of L. rhamnosus GG. L. brevis KU15152 did not produce harmful enzymes, such as β-glucuronidase, indicating that it could be used as a potential probiotic. The anti-inflammatory potential of L. brevis KU15152 was determined in HT-29 cells. Treatment with L. brevis KU15152 suppressed the production of interleukin-8 without inducing significant cytotoxicity. The downregulatory effects of L. brevis KU15152 were involved in the suppression of nuclear factor-kappa B activation mediated by the extracellular signal-regulated kinase and Akt signaling pathways. Collectively, these data suggest that L. brevis KU15152 can be used in developing therapeutic and prophylactic products to manage and treat aLTA-induced intestinal damage.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.21-29
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• 2023

The poor outcome of advanced ovarian cancer under conventional therapy necessitates new strategies to improve therapeutic efficacy. β-glucosidase (encoded by GBA) is a lysosomal enzyme and is involved in sphingolipids metabolism. Recent studies revealed that β-glucosidase plays a role in cancer development and chemoresistance. In this work, we systematically evaluated the expression and role of GBA in ovarian cancer. Our work demonstrates that inhibition of β-glucosidase has therapeutic potential for ovarian cancer. Gene Expression Profiling Interactive Analysis database, western blot and immunohistochemistry analyses of patient samples demonstrated that GBA mRNA and protein expression levels were significantly increased in ovarian cancer compared to normal tissues. Functional studies using gainof-function and loss-of-function approaches demonstrated that GBA overexpression did not affect growth and migration but alleviated cisplatin's efficacy in ovarian cancer cells. In addition, GBA depletion resulted in growth inhibition, apoptosis induction, and enhancement of cisplatin's efficacy. Of note, we found that GBA inhibition specifically decreased receptor tyrosine kinase AXL level, leading to the suppression of AXL-mediated signaling pathways. Our data suggest that GBA represents a promising target to inhibit AXL signaling and overcome cisplatin resistance in ovarian cancer.

• 한국생물공학회:학술대회논문집
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• 2003.04a
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• pp.743-746
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• 2003

The major pathological lesion in Parkinson's disease(PD) is selective degeneration and loss of pigmented dopaminergic neurons in substantia nigra (SN). Although the initial cause and subsequent molecular signaling mechanisms leading to the dopaminergic cell death underlying the PD process is elusive, the potent neurotrophic factors (NTFs), brain derived neurotrophic factor (BDNF) and glial cell line derived neurotrophic factor (GDNF), are known to exert dopaminergic neuroprotection both in vivo and in vitro models of PD employing the neurotoxin, MPTP. BDNF and its receptor, trkB are expressed in SN dopaminergic neurons and their innervation target. Thus, neurotrophins may have autocrine, paracrine and retrograde transport effects on the SN dopaminergic neurons. This study determined the BDNF secretion from SN dopaminergic neurons by ELISA. Regulation of BDNF synthesis/release and changes in signaling pathways are monitored in the presence of free radical donor, NO donor and mitochondrial inhibitors. Also, this study shows that BDNF is able to promote survival and phenotypic differentiation of SN dopaminergic neurons in culture and protect them against MPTP-induced neurotoxicity via MAP kinase pathway.

• 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.

• Toxicological Research
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• v.33 no.4
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• pp.273-282
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• 2017

Chemoprevention entails the use of synthetic agents or naturally occurring dietary phytochemicals to prevent cancer development and progression. One promising chemopreventive agent, procyanidin, is a naturally occurring polyphenol that exhibits beneficial health effects including anti-inflammatory, antiproliferative, and antitumor activities. Currently, many preclinical reports suggest procyanidin as a promising lead compound for cancer prevention and treatment. As a potential anticancer agent, procyanidin has been shown to inhibit the proliferation of various cancer cells in "in vitro and in vivo". Procyanidin has numerous targets, many of which are components of intracellular signaling pathways, including proinflammatory mediators, regulators of cell survival and apoptosis, and angiogenic and metastatic mediators, and modulates a set of upstream kinases, transcription factors, and their regulators. Although remarkable progress characterizing the molecular mechanisms and targets underlying the anticancer properties of procyanidin has been made in the past decade, the chemopreventive targets or biomarkers of procyanidin action have not been completely elucidated. This review focuses on the apoptosis and tumor inhibitory effects of procyanidin with respect to its bioavailability.

• BMB Reports
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• v.55 no.12
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• pp.577-586
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• 2022

Stress granules (SGs) are stress-induced subcellular compartments, which carry out a particular function to cope with stress. These granules protect cells from stress-related damage and cell death through dynamic sequestration of numerous ribonucleoproteins (RNPs) and signaling proteins, thereby promoting cell survival under both physiological and pathological condition. During tumorigenesis, cancer cells are repeatedly exposed to diverse stress stimuli from the tumor microenvironment, and the dynamics of SGs is often modulated due to the alteration of gene expression patterns in cancer cells, leading to tumor progression as well as resistance to anticancer treatment. In this mini review, we provide a brief discussion about our current understanding of the fundamental roles of SGs during physiological stress and the effect of dysregulated SGs on cancer cell fitness and cancer therapy.

• The Korean Journal of Pain
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• v.37 no.4
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• pp.288-298
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• 2024

Nerve growth factor (NGF) is a neurotrophic protein that has crucial roles in survival, growth and differentiation. It is expressed in neuronal and non-neuronal tissues. NGF exerts its effects via two types of receptors including the high affinity receptor, tropomyosin receptor kinase A and the low affinity receptor p75 neurotrophin receptor highlighting the complex signaling pathways that underlie the roles of NGF. In pain perception and transmission, multiple studies shed light on the effects of NGF on different types of pain including inflammatory, neuropathic, cancer and visceral pain. Also, the binding of NGF to its receptors increases the availability of many nociceptive receptors such as transient receptor potential vanilloid 1, transient receptor potential ankyrin 1, N-methyl-D-aspartic acid, and P2X purinoceptor 3 as well as nociceptive transmitters such as substance P and calcitonin gene-related peptide. The role of NGF in pain has been documented in pre-clinical and clinical studies. This review aims to shed light on the role of NGF and its signaling in different types of pain.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.2
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• pp.57-64
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• 2007

Ischemic preconditioning (IPC) is known to protect the heart against ischemia/reperfusion (IR)-induced injuries, and regional differences in the mitochondrial antioxidant state during IR or IPC may promote the death or survival of viable and infarcted cardiac tissues under oxidative stress. To date, however, the interplay between the mitochondrial antioxidant enzyme system and the level of reactive oxygen species (ROS) in the body has not yet been resolved. In the present study, we examined the effects of IR- and IPC-induced oxidative stresses on mitochondrial function in viable and infarcted cardiac tissues. Our results showed that the mitochondria from viable areas in the IR-induced group were swollen and fused, whereas those in the infarcted area were heavily damaged. IPC protected the mitochondria, thus reducing cardiac injury. We also found that the activity of the mitochondrial antioxidant enzyme system, which includes manganese superoxide dismutase (Mn-SOD), was enhanced in the viable areas compared to the infarcted areas in proportion with decreasing levels of ROS and mitochondrial DNA (mtDNA) damage. These changes were also present between the IPC and IR groups. Regional differences in Mn-SOD expression were shown to be related to a reduction in mtDNA damage as well as to the release of mitochondrial cytochrome c (Cyt c). To the best of our knowledge, this might be the first study to explore the regional mitochondrial changes during IPC. The present findings are expected to help elucidate the molecular mechanism involved in IPC and helpful in the development of new clinical strategies against ischemic heart disease.

• Journal of Dental Rehabilitation and Applied Science
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• v.36 no.3
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• pp.145-157
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• 2020

Purpose: This study was to determine the possible effects of trichloroacetic acid (TCA) and epidermal growth factor (EGF) through cell survival genes of the PI3K-AKT signaling pathway when applying an hydrophobically modified glycol chitosan (HGC)-based nanocontrolled release system to human gingival fibroblasts in oral soft tissue regeneration. Materials and Methods: An HGC-based nano-controlled release system was produced, followed by the loading of TCA and EGF. The group was divided into control (CON), TCA-loaded nano-controlled release system (EXP1), and the TCA- and EGF- individually loaded nano-controlled release system (EXP2). A total for 29 genes related to the PI3K-AKT signaling pathway were analyzed after 48h of culture in human gingival fibroblasts. Real-time PCR, 1- way ANOVA and multiple regression analysis were performed. Results: Cell survival genes were significantly upregulated in EXP1 and EXP2. From multiple regression analysis, ITGB1 was determined to be the most influential factor for AKT1 expression. Conclusion: The application of TCA and EGF through the HGC-based nano-controlled release system can up-regulate the cell survival pathway.