• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.682-691
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• 2023

Cell transformation induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the cancer preventive efficacy of licochalcone D (LicoD), a chalcone derivative in licorice extract, in EGF and TPA-induced transformed skin keratinocyte cells. LicoD effectively suppressed EGF-induced cell proliferation and anchorage-independent colony growth. EGF and TPA promoted the S phase of cell cycle, while LicoD treatment caused G1 phase arrest and down-regulated cyclin D1 and up-regulated p21 expression associated with the G1 phase. LicoD also induced apoptosis and increased apoptosis-related proteins such as cleaved-caspase-3, cleaved-caspase-7, and Bax (Bcl2-associated X protein). We further investigated the effect of LicoD on the AKT signaling pathway involved in various cellular processes and found decreased p-AKT, p-GSK3β, and p-NFκB expression. Treatment with MK-2206, an AKT pharmacological inhibitor, suppressed EGF-induced cell proliferation and transformed colony growth. In conclusion, this study demonstrated the potential of LicoD as a preventive agent for skin carcinogenesis.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.661-673
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• 2023

Treatment of colorectal cancer (CRC) has always been challenged by the development of resistance. We investigated the antiproliferative activity of licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata, in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including pEGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of sub-G1 cells and arrested the cell cycle at the G1 phase. Taken together LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.

• The Journal of Korean Medical History
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• v.35 no.2
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• pp.45-67
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• 2022

Currently, there are about 20,000 or so known ancient medical texts from the East Asian medical traditions. Although the most famous texts are widely known, many texts still exist only as original manuscripts. We are interested exploring these texts to uncover the potential benefits of their therapeutic knowledge. This study aims to develop a database program that automatically converts the treatment skills described in the text version into a more structured version. In the previous study, our team analyzed patterns in the way that treatment skills are described and then tried to design a database program algorithm that identified every meaningful keyword used to describe treatment skills and put that word in the right cell of a structured table. This study continues the development of this program. East Asian medical herbal treatment information is broken down into 4 elements: the first one is the name or title of treatment skills, and the second is the symptoms to which the treatment is applied, the third is ingredients used, the fourth is how information is processed and the indications taken. This study presents the algorithm's principles on how to analyze and structure the fourth element, the processing of information and taking of indications, which is described in a form of ancient natural language.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.103-103
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• 2022

Ganghwaljetongyeum (GHJTY) is a complex herbal decoction comprising 18 plants; it is used to treat arthritis. In order to develop a new anti-arthritic herbal medication, we selected 5 out of 18 GHJTY plants by using bioinformatics analysis. The new medication, called ChondroT, comprised water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex. This study was designed to investigate its chondroprotective and anti-inflammatory effects to develop an anti-arthritic herb medicine. ChondroT was validated using a convenient and accurate high-performance liquid chromatography. photodiode array (HPLC-PDA) detection method for simultaneous determination of its seven reference components. The concentrations of the seven marker constituents were in the range of 0.81-5.46 mg/g. The chondroprotective effects were evaluated based on SW1353 chondrocytes and matrix metalloproteinase 1 (MMP1) expression. In addition, the anti-inflammatory effects of ChondroT were studied by Western blotting of pro-inflammatory enzymes and by enzyme-linked immunosorbent assay (ELISA) of inflammatory mediators in lipopolysaccharides (LPS)-induced RAW264.7 cells. ChondroT enhanced the growth of SW1353 chondrocytes and also significantly inhibited IL-1β-induced MMP-1 expression. However, ChondroT did not show any effects on the growth of HeLa and RAW264.7 cells. The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was induced by LPS in RAW264.7 cells, which was significantly decreased by pre-treatment with ChondroT. In addition, ChondroT reduced the activation of NF-κB and production of inflammatory mediators, such as IL-1β, IL-6, PGE2, and nitric oxide (NO) in LPS-induced RAW264.7 cells. These results show that ChondroT exerted a chondroprotective effect and demonstrated multi-target mechanisms related to inflammation and arthritis. In addition, the suppressive effect was greater than that exhibited by GHJTY, suggesting that ChondroT, a new complex herbal medication, has therapeutic potential for the treatment of arthritis.

• Journal of Biomedical Engineering Research
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• v.44 no.6
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• pp.428-442
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• 2023

In this study, we have a goal to develop usability evaluation guidelines for heuristic-based artificial intelligence-based Software as a Medical Device (SaMD) in the medical field. We conducted a gap analysis between medical hardware (H/W) and non-medical software (S/W) based on ten heuristic principles. Through severity assessments, we identified 69 evaluation domains and 112 evaluation criteria aligned with the ten heuristic principles. Subsequently, we categorized each evaluation domain into five types, including user safety, data integrity, regulatory compliance, patient therapeutic effectiveness, and user convenience. We proposed usability evaluation guidelines that apply the newly derived heuristic-based Software as a Medical Device (SaMD) evaluation factors to the risk management process. In the discussion, we also have proposed the potential applications of the research findings and directions for future research. We have emphasized the importance of the judicious application of AI technology in the medical field and the evaluation of usability evaluation and offered valuable guidelines for various stakeholders, including medical device manufacturers, healthcare professionals, and regulatory authorities.

• Journal of Animal Reproduction and Biotechnology
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• v.38 no.3
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• pp.109-120
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• 2023

Background: Pluripotent stem cells (PSCs) including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) offer the immense therapeutic potential in stem cell-based therapy of degenerative disorders. However, clinical trials of human ESCs cause heavy ethical concerns. With the derivation of iPSCs established by reprogramming from adult somatic cells through the transgenic expression of transcription factors, this problems would be able to overcome. In the present study, we tried to differentiate porcine iPSCs (piPSCs) into endothelial cells (ECs) for stem cell-based therapy of vascular diseases. Methods: piPSCs (OSKMNL) were induced to differentiation into ECs in four differentiation media (APEL-2, APEL-2 + 50 ng/mL of VEGF, EBM-2, EBM-2 + 50 ng/mL of VEGF) on cultured plates coated with matrigel^® (1:40 dilution with DMEM/F-12 medium) for 8 days. Differentiation efficiency of these cells were exanimated using qRT-PCR, Immunocytochemistry, Western blotting and FACS. Results: As results, expressions of pluripotency-associated markers (OCT-3/4, SOX2 and NANOG) were higher observed in all porcine differentiated cells derived from piPSCs (OSKMNL) cultured in four differentiation media than piPSCs as the control, whereas endothelial-associated marker (CD-31) in the differentiated cells was not expressed. Conclusions: It can be seen that piPSCs (OSKMNL) were not suitable to differentiate into ECs in the four differentiation media unlike porcine epiblast stem cells (pEpiSCs). Therefore, it would be required to establish a suitable PSCs for differentiating into ECs for the treatment of cardiovascular diseases.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.784-794
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• 2023

Background: ginsenoside Rg5 is a rare ginsenoside with known hypoglycemic effects in diabetic mice. This study aimed to explore the effects of ginsenoside Rg5 on skin wound-healing in the Lepr^db/db mutant (db/db) mice (C57BL/KsJ background) model and the underlying mechanisms. Methods: Seven-week-old male C57BL/6J, SLC7A11-knockout (KO), the littermate wild-type (WT), and db/db mice were used for in vivo and ex vivo studies. Results: Ginsenoside Rg5 provided through oral gavage in db/db mice significantly alleviated the abundance of apoptotic cells in the wound areas and facilitated skin wound healing. 50 μM ginsenoside Rg5 treatment nearly doubled the efferocytotic capability of bone marrow-derived dendritic cells (BMDCs) from db/db mice. It also reduced NF-κB p65 and SLC7A11 expression in the wounded areas of db/db mice dose-dependently. Ginsenoside Rg5 physically interacted with SLC7A11 and suppressed the cystine uptake and glutamate secretion of BMDCs from db/db and SLC7A11-WT mice but not in BMDCs from SLC7A11-KO mice. In BMDCs and conventional type 1 dendritic cells (cDC1s), ginsenoside Rg5 reduced their glycose storage and enhanced anaerobic glycolysis. Glycogen phosphorylase inhibitor CP-91149 almost abolished the effect of ginsenoside Rg5 on promoting efferocytosis. Conclusion: ginsenoside Rg5 can suppress the expression of SLC7A11 and inhibit its activity via physical binding. These effects collectively alleviate the negative regulations of SLC7A11 on anaerobic glycolysis, which fuels the efferocytosis of dendritic cells. Therefore, ginsenoside Rg5 has a potential adjuvant therapeutic reagent to support patients with wound-healing problems, such as diabetic foot ulcers.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.766-772
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• 2023

Background: Korean Red Ginseng (KRG) is an effective anti-stress treatment. In this study, we investigated the therapeutic potential effects of KRG on relieving stress in a general population using transcriptome analysis. Methods: We conducted an 8-week clinical pilot study on 90 healthy men who reported stress. The study was completed by 43 participants in the KRG group and 44 participants in the placebo group. Participants were randomized 1:1 to the KRG and placebo groups. We evaluated the stress by stress response inventory (SRI) at baseline and 8 weeks. The main outcomes were changes in the levels of neurotransmitters (NTs) and NT-related gene expression. NTs were analyzed using automated (GC) content, and levels of gene expression were measured by reads per kilobase of transcript per million mapped reads (RPKM). Results: The KRG group showed significantly preserved epinephrine decrease compared with placebo group at 8 weeks (changes in epinephrine, KRG vs. placebo; -1623.2 ± 46101.5 vs. -35116.3 ± 86288.2, p = 0012). Among subjects who higher SRI score, meaning stress increased compared to baseline, the KRG group showed a smaller decrease in serotonin than the placebo group (changes in serotonin, KRG vs. placebo; -2627.5 ± 5859.1 vs, -8087.4 ± 7162.4, p = 0.005) and a smaller increase in cortisol than the placebo group (changes in cortisol, KRG vs. placebo; 1912.7 ± 10097.75 vs. 8046.2 ± 8050.6 , p = 0.019) in subgroup analysis. Transcriptome findings indicated that KRG intake affects gene expression related with metabolism of choline, adrenalin, and monoamine. Conclusion: These findings suggest that KRG has beneficial effects on the amelioration of stress response in NTs, and this effect is more prominent in stressful situations. Further clinical studies are required to confirm the anti-stress effect of KRG.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.34 no.4
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• pp.192-203
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• 2023

Digital therapeutics based on software, such as artificial intelligence, virtual reality, games, and smartphone applications, are in the spotlight as new therapeutic alternatives in child and adolescent psychiatry. It draws attention to overcoming conventional therapeutics' limitations, such as toxicity, cost, and accessibility, and encourages patients to participate in the treatment attractively. The growth potential of the digital therapeutics market for psychiatric disorders in children and adolescents in Korea and abroad has been highlighted. Clinical studies and Food and Drug Administration approvals for digital therapeutics have increased, and cases approved by the Ministry of Food and Drug Safety have emerged in Korea. As seen above, digital transformation in child and adolescent psychiatry will change treatment paradigms significantly. Therefore, as this new field has just begun to emerge, it is necessary to verify the effectiveness and scope of the application of digital therapeutics and consider preparing a compensation system and institutional arrangements. Accordingly, this study analyzed the development trends and application status of digital therapeutics in children and adolescents and presented limitations and development directions from the perspective of application in healthcare. Further, the study is expected to identify the utility and limitations of digital therapeutics for children and adolescents and establish effective application measures.

• Journal of Veterinary Science
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• v.25 no.1
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• pp.12.1-12.10
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• 2024

Background: Staphylococcus aureus and S. pseudintermedius are the major etiological agents of staphylococcal infections in humans, livestock, and companion animals. The misuse of antimicrobial drugs has led to the emergence of antimicrobial-resistant Staphylococcus spp., including methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. pseudintermedius (MRSP). One novel therapeutic approach against MRSA and MRSP is a peptide nucleic acid (PNA) that can bind to the target nucleotide strands and block expression. Previously, two PNAs conjugated with cell-penetrating peptides (P-PNAs), antisense PNA (ASP)-cmk and ASP-deoD, targeting two essential genes in S. aureus, were constructed, and their antibacterial activities were analyzed. Objectives: This study analyzed the combined antibacterial effects of P-PNAs on S. aureus and S. pseudintermedius clinical isolates. Methods: S. aureus ATCC 29740 cells were treated simultaneously with serially diluted ASP-cmk and ASP-deoD, and the minimal inhibitory concentrations (MICs) were measured. The combined P-PNA mixture was then treated with S. aureus and S. pseudintermedius veterinary isolates at the determined MIC, and the antibacterial effect was examined. Results: The combined treatment of two P-PNAs showed higher antibacterial activity than the individual treatments. The MICs of two individual P-PNAs were 20 and 25 µM, whereas that of the combined treatment was 10 µM. The application of a combined treatment to clinical Staphylococcus spp. revealed S. aureus isolates to be resistant to P-PNAs and S. pseudintermedius isolates to be susceptible. Conclusions: These observations highlight the complexity of designing ASPs with high efficacy for potential applications in treating staphylococcal infections in humans and animals.