• The Korean Journal of Physiology and Pharmacology
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• v.27 no.3
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• pp.197-208
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• 2023

Dysregulation of certain long non-coding RNAs may facilitate tumor initiation and progression. However, numerous carcinogenesis-related long noncoding RNAs have not been characterized. The goal of this study was to elucidate the role of LINC00562 in gastric cancer (GC). The expression of LINC00562 was analyzed using real-time quantitative PCR and Western blotting. The proliferative capacity of GC cells was determined using Cell Counting Kit-8 and colony-formation assays. The migration of GC cells were evaluated using wound-healing assays. The apoptosis of GC cells was assessed by measuring the expression levels of apoptosis-related proteins (Bax and Bcl-2). Xenograft models in nude mice were constructed for in vivo functional analysis of LINC00562. The binding relationship between miR-4636 and LINC00562 or adaptor protein complex 1 sigma 3 (AP1S3), obtained from public databases, was confirmed using dual-luciferase and RNA-binding protein immunoprecipitation experiments. LINC00562 was expressed in GC cells at high levels. Knockdown of LINC00562 repressed GC cell growth and migration, promoted apoptosis in vitro, and inhibited tumor growth in nude mouse models. LINC00562 directly targeted miR-4636, and miR-4636 depletion restored the GC cell behavior inhibited by LINC00562 absence. AP1S3, an oncogene, binds to miR-4636. MiR-4636 downregulation increased AP1S3 level, restoring GC cell malignant behaviors inhibited by AP1S3 downregulation. Thus, LINC00562 exerts carcinogenic effects on GC development by targeting miR-4636-mediated AP1S3 signaling.

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.3
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• pp.59-67
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• 2023

Purpose : Epithelial-to-mesenchymal transition (EMT) is recognized as an important cellular response in metastatic proceduresand characterized by loss of cellular polarity as well as gain of mesenchymal features, which enables migration and invasion. Hepatocellular carcinoma (HCC) is one of the most common primary carcinomas in the liver and exhibits a poor prognosis due to frequent extrahepatic metastasis. Taraxacum officinale has been used for a long time in oriental medicine because of its various pharmacological activitiessuch as anti-rheumatic, anti-inflammatory, antioxidative, and anticarcinogenic activities. In this study, the anti-metastatic activity of T. officinale water extract (TOWE) and ethanol extract (TOEE) was investigated through the regulation of EMT in the Huh7 cells. Methods : The effects of TOWE and TOEE on migratory and invasive activities were investigated by wound healing and in vitro invasion assays. Western blot analysis was also applied to analyze protein expression levels associated with EMT and their upstream transcription factors in Huh7 cells. Results : TOWE and TOEE treatment potently inhibited migration and invasion of Huh7 cells compared to the untreated group. Both extracts treatment inhibited protein expression levels of N-cadherin, matrix metalloproteinase (MMP)-9, and vimentin while E-cadherin was significantly accelerated. In addition, the activated status of transcription factors, Snail, nuclear factor (NF)-κ B, and zinc finger E-box binding homeobox (ZEB)1 was also inhibited with statistical significance. In comparison to both extracts, TOEE more potently attenuated migration, invasion, and EMT markers as well as their transcription factors in Huh7 cells than TOWE, which means that TOEE might possess more functional phytochemicals than TOWE. Conclusion : Consequently, TOWE and TOEEattenuated metastatic activity of hepatocellular carcinoma through the regulation of EMT markers and their transcription factors in Huh7 cells, which means that T. officinale might be a promising strategy for a chemopreventive agent against HCC metastasis.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.126-136
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• 2022

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.170-178
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• 2022

The airway epithelium is equipped with the ability to resist respiratory disease development and airway damage, including the migration of airway epithelial cells and the activation of TLR3, which recognizes double-stranded (ds) RNA. Primary cilia on airway epithelial cells are involved in the cell cycle and cell differentiation and repair. In this study, we used Beas-2B human bronchial epithelial cells to investigate the effects of the TLR3 agonist polyinosinic:polycytidylic acid [Poly(I:C)] on airway cell migration and primary cilia (PC) formation. PC formation increased in cells incubated under serum deprivation. Migration was faster in Beas-2B cells pretreated with Poly(I:C) than in control cells, as judged by a wound healing assay, single-cell path tracking, and a Transwell migration assay. No changes in cell migration were observed when the cells were incubated in conditioned medium from Poly(I:C)-treated cells. PC formation was enhanced by Poly(I:C) treatment, but was reduced when the cells were exposed to the ciliogenesis inhibitor ciliobrevin A (CilioA). The inhibition of Beas-2B cell migration by CilioA was also assessed and a slight decrease in ciliogenesis was detected in SARS-CoV-2 spike protein (SP)-treated Beas-2B cells overexpressing ACE2 compared to control cells. Cell migration was decreased by SP but restored by Poly(I:C) treatment. Taken together, our results demonstrate that impaired migration by SP-treated cells can be attenuated by Poly(I:C) treatment, thus increasing airway cell migration through the regulation of ciliogenesis.

• Korean Journal of Agricultural Science
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• v.48 no.4
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• pp.1003-1013
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• 2021

Thioredoxin (TRX) protein is an antioxidant responsible for reducing other proteins by exchanging cysteine thiol-disulfide and is also known for its anti-allergic and anti-aging properties. On the other hand, epidermal growth factor (EGF) is an important material used in the cosmetics industry and an essential protein necessary for dermal wound healing facilitated by the proliferation and migration of keratinocytes. EGF also assists in the formation of granulation tissues and stimulates the motility of fibroblasts. Hence, genetically modified soybeans were developed to overexpress these industrially important proteins for mass production. A single-dose oral-toxicity-based study was conducted to evaluate the potential toxic effects of TRX and EGF proteins, as safety assessments are necessary for the commercial use of seed-specific protein-expressing transgenic soybeans. To achieve this rationale, TRX and EGF proteins were mass purified from recombinant E. coli. The single-dose oral-toxicity tests of the TRX and EGF proteins were carried out in six-week old male and female Institute of Cancer Research (ICR) mice. The initial evaluation of the single-dose TRF and EGF treatments was based on monitoring the toxicity signatures and mortality rates among the mice, and the resultant mortality rates did not show any specific clinical symptoms related to the proteins. Furthermore, no significant differences were observed in the weights between the treatment and control groups of male and female ICR mice. After 14 days of treatment, no differences were observed in the autopsy reports between the various treatment and control groups. These results suggest that the minimum lethal dose of TRX and EGF proteins is higher than the allowed 2,000 mg·kg^-1 limit.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.479-491
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• 2023

Background: Hepatocellular carcinoma (HCC) has a high incidence and is one of the highest mortality cancers when advanced stage is proceeded. However, Anti-cancer drugs available for treatment are limited and new anti-cancer drugs and new ways to treat them are minimal. We examined that the effects and possibility of Red Ginseng (RG, Panax ginseng Meyer) as new anti-cancer drug on HCC by combining network pharmacology and molecular biology. Materials and Methods: Network pharmacological analysis was employed to investigate the systems-level mechanism of RG focusing on HCC. Cytotoxicity of RG was determined by MTT analysis, which were also stained by annexin V/PI staining for apoptosis and acridine orange for autophagy. For the analyze mechanism of RG, we extracted protein and subjected to immunoblotting for apoptosis or autophagy related proteins. Results: We constructed compound-target network of RG and identified potential pathways related to HCC. RG inhibited growth of HCC through acceleration of cytotoxicity and reduction of wound healing ability of HCC. RG also increased apoptosis and autophagy through AMPK induction. In addition, its ingredients, 20S-PPD (protopanaxadiol) and 20S-PPT (protopanaxatriol), also induced AMPK mediated apoptosis and autophagy. Conclusion: RG effectively inhibited growth of HCC cells inducing apoptosis and autophagy via ATG/AMPK in HCC cells. Overall, our study suggests possibility as new anti-cancer drug on HCC by proof for the mechanism of the anti-cancer action of RG.

• Medical Lasers
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• v.8 no.2
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• pp.50-58
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• 2019

Background and Objectives Low-level light therapy (LLLT) is an application of low-power light for various purposes such as promoting tissue repair, reducing inflammation, causing analgesia, etc. A previous study suggested the effect of light emitting diode (LED) light with the wavelength of 740 nm for promoting wound healing of corneal epithelial cells. This current study aimed to confirm the effect of LLLT for managing inflammation of a dry eye disease (DED) mouse model. Materials and Methods A total of 50C57BL/6 female mice were randomly grouped into 5 groups to compare the effect of LLLT:1) Control group, 2) Only LLLT group, 3) Dry eye group, 4) LLLT in dry eye group, and 5) Early treatment group. DED was induced with 4 daily injections of scopolamine hydrobromide and desiccation stress for 17 days, and LLLT at 740 nm was conducted once every 3 days. To analyze the effect of LLLT on the DED mouse model, tear volume, corneal surface irregularities, and fluorescence in stained cores were measured, and the level of inflammation was assessed with immunohistochemistry. Results The DED mouse model showed significant deterioration in the overall eye condition. After LLLT, the amount of tear volume was increased, and corneal surface irregularities were restored. Also, the number of neutrophils and the level of inflammatory cytokines significantly decreased as well. Conclusion This study showed that LLLT at 740 nm was effective in controlling the corneal conditions and the degree of inflammation in DED. Such findings may suggest therapeutic effects of LLLT at 740 nm on DED.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.640-647
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• 2023

The skin, the largest organ in the body, undergoes age-related changes influenced by both intrinsic and extrinsic factors. The primary external factor is photoaging which causes hyperpigmentation, uneven skin surface, deep wrinkles, and markedly enlarged capillaries. In the human dermis, it decreases fibroblast function, resulting in a lack of collagen structure and also decreases keratinocyte function, which compromises the strength of the protective barrier. In this study, we found that treatment with γ-aminobutyric acid (GABA) had no toxicity to skin fibroblasts and GABA enhanced their migration ability, which can accelerate skin wound healing. UVB radiation was found to significantly induce the production of matrix metalloproteinase 1 (MMP-1), but treatment with GABA resulted in the inhibition of MMP-1 production. We also investigated the enhancement of filaggrin and aquaporin 3 in keratinocytes after treatment with GABA, showing that GABA can effectively improve skin moisturization. In vivo experiments showed that oral administration of GABA significantly improved skin wrinkles and epidermal thickness. After the intake of GABA, there was a significant decrease observed in the increase of skin thickness measured by calipers and erythema. Additionally, the decrease in skin moisture and elasticity in hairless mice exposed to UVB radiation was also significantly restored. Overall, this study demonstrates the potential of GABA as functional food material for improving skin aging and moisturizing.

• Journal of Korean Dental Science
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• v.16 no.2
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• pp.172-181
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• 2023

Purpose: To investigate the effect of epidermal growth factor (EGF) with collagen matrix (CM) for increasing gingival thickness. Materials and Methods: In five mongrel dogs, bilateral gingival defects were surgically made on the maxillary canines. After two months, either a subepithelial connective tissue graft (group SCTG) or CM with EGF (0.1 ug/ml, group EGF) was grafted, and the flap was coronally positioned to cover the graft materials. The animals were sacrificed after three months. Intraoral scanning was performed for soft tissue analysis. Histologic and histomorphometric analyses were performed. Result: Two animals exhibited wound dehiscence during the healing phase, leaving three for analysis. No statistically significant difference was found in soft tissue changes (P>0.05). The level of gingival margin (GM) increased in both groups (1.02±0.74 mm in group SCTG vs. 1.24±0.83 mm in group EGF). Linear increases at the GM pre-augmentation in the soft tissue profile were 1.08±0.58 mm in group SCTG and 0.96±0.73 mm in group EGF. Histomorphometric parameters (keratinized tissue height, tissue thickness, and rete peg density) were not significantly different between the groups (P>0.05). Conclusion: EGF loaded onto CM led to comparable gingival phenotype enhancement to SCTG.

• Journal of Adhesion and Interface
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• v.24 no.4
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• pp.113-119
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• 2023

Since it was reported that the unusual amino acid DOPA in synergy with lysine and histidine residues found in mussel adhesive proteins plays a pivotal role in mussel adhesion in underwater environments, there has been a burgeoning development of various catecholamines-based adhesives for biomedical applications. Among these, catechol-conjugated chitosan, containing catecholamine, featuring multiple catechol groups within its aminerich chitosan backbone, has found versatile utility in fields, such as tissue adhesion, wound dressing, tissue healing, hemostats, drug delivery systems, and tissue engineering scaffolds. Significantly, chitosan-catechol is a mussel-inspired material approved by both US Food and Drug Administration (FDA) and KR Ministry of Food and Drug Safety (MFDS) for its effectiveness in hemostasis. This review focuses on 1) general aspects of catechol-conjugated chitosan, highlighting catechol group integration into chitosan backbones, 2) examination of proposed mechanisms of hemostasis, and 3) exploration of diverse physical forms, including solution, hydrogels, patches, and thin films with practical applications inapplicable to hemostasis.