• Journal of Korea Entertainment Industry Association
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• v.13 no.1
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• pp.217-223
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• 2019

Colon cancer is the most common form of cancer diagnosis in worldwide. There are growing interests in the health benefits associated with consumption of fruits and vegetables, especially for the prevention of cancer, cardiovascular or other chronic diseases. The objective of the present study was to investigate the antioxidant and anticancer activities of natural product, guarana(GR) and graviola(GV) in human colon carcinoma HCT-116 cells. MTT assay, flow cytometry analysis were employed to investigate the anticancer mechanism and DPPH assay was determined to the antioxidant activity to scavenge free radicals in extract of these. All two extracts showed significantly antioxidant activity at 50mg/ml of concentration. GR and GV reduced HCT-116 cell proliferation in a dose dependent manner. Specially GR treatment(96.65±3.71) also significantly increased the sub-G1 population more than GV(79.58±2.87) treatment in HCT-116 at the concentration of 10mg/ml, as shown by flow cytometry assay. Statistical analyses revealed GR and GV exhibited significantly high (P < 0.05) cytotoxicity in HCT-116. These findings indicate that GN and GV may serve as novel therapeutic agents for colon cancer treatment and future leads for drug development.

• BMB Reports
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• v.56 no.2
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• pp.96-101
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• 2023

Particulate matter is an air pollutant composed of various components, and has adverse effects on the human body. Particulate matter is known to induce cell death by generating an imbalance in the antioxidant system; however, the underlying mechanism has not been elucidated. In the present study, we demonstrated the cytotoxic effects of the size and composition of particulate matter on small intestine cells. We found that particulate matter 2.5 (PM_2.5) with extraction ion (EI) components (PM_2.5 EI), is more cytotoxic than PM containing only polycyclic aromatic hydrocarbons (PAHs). Additionally, PM-induced cell death is characteristic of ferroptosis, and includes iron accumulation, lipid peroxidation, and reactive oxygen species (ROS) generation. Furthermore, ferroptosis inhibitor as liproxstatin-1 and iron-chelator as deferiprone attenuated cell mortality, lipid peroxidation, iron accumulation, and ROS production after PM_2.5 EI treatment in human small intestinal cells. These results suggest that PM_2.5 EI may increase ferroptotic-cell death by iron accumulation and ROS generation, and offer a potential therapeutic clue for inflammatory bowel diseases in human small intestinal cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.5
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• pp.155-162
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• 2022

Even after testing negative for COVID-19, some patients continue to struggle with a variety of symptoms such as fatigue, shortness of breath, gastrointestinal problems and neurological problems. The World Health Organization (WHO) defined long COVID (Post COVID-19 conditions) as "A disease occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months, that cannot be explained by an alternative diagnosis." As a possible pathological mechanism of long COVID, three hypotheses are proposed: the persistence of the infectious state due to the residual virus, the persistent inflammatory response, and the autoimmune response. The main symptoms of long COVID are shortness of breath (dyspnea), abdominal pain and dyspepsia, fatigue, cognitive problems (brain fog), anosmia and dysgeusia, and chest pain, palpitations and tachycardia. In the Chinese guidelines, COVID-19 patients were divided into mild, moderate, severe, and recovery, and prescriptions with effective therapeutic effects were summarized to encourage combined treatment of chinese and western medicine. Globally, only symptomatic therapy is recommended for long COVID, but a specific treatment has not yet been proposed. Recently, morbidity code for post COVID-19 conditions was created, and it is planned to announce guidelines for long COVID treatment and management in the first half of 2023. In line with this trend, the Korean medical community needs to make efforts to prepare treatment guidelines for patients with long COVID.

• Safety and Health at Work
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• v.14 no.1
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• pp.118-123
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• 2023

Background: Chronic exposure to silica is related with the provocation of an inflammatory response and oxidative stress mechanism. Vitamin D has multiple benefits in biological activities particularly respiratory system disease. Method: In this research, 20 male Wistar rats were randomly allocated into four groups (5 rats /group) as follow: Group1 received saline as (negative control) group. The group 2 received a single IT instillation of silica (positive control) group; the group 3 was co-administrated with single IT silica and Vitamin D (20 mg/kg/day) daily for a period of 90 days. The rats of group 4 received Vitamin D daily for a period of 90 days. Results: Silica significantly increased serum and lung total Oxidant Status (TOS). Meanwhile, silica reduced serum and lung total antioxidant capacity (TAC), GSH and tumor necrosis factor-α (TNF-a). Vitamin D treatment meaningfully reversed oxidative stress, antioxidants status and inflammatory response. Also, Vitamin D improved histopathological changes caused by silica. Conclusion: These findings indicate that Vitamin D exerts protective effects against silica-induced lung injury. It seems that Vitamin D has potential use as a therapeutic object for silica induced lung injure.

• BMB Reports
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• v.56 no.5
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• pp.265-274
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• 2023

Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. Nevertheless, tumors depend on residual DNA repair abilities to survive the DNA damage induced by genotoxic stress. This is why only isolated DNA repair signaling is inactivated in cancer cells. DNA DSB repair signaling contributes to general mechanism for various types of lesions in diverse cell cycle phases. DNA DSB repair genes are frequently mutated and amplified in cancer; however, limited data exist regarding the overall genomic prospect and functional result of these modifications. We list the DNA repair genes and related E3 ligases. Mutation and expression frequencies of these genes were analyzed in COSMIC and TCGA. The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. This study provides a broad list of candidate genes as potential biomarkers for genomic instability and novel therapeutic targets in cancer. As a DSB related proteins considerably appear the possibilities for targeting DNA repair defective tumors or hyperactive DNA repair tumors. Based on recent research, we describe the relationship between unstable DSB repairs and DSB-related E3 ligases.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.365-374
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• 2023

Crohn's disease (CD) is a chronic inflammatory illness of the digestive system with unknown etiology, and its incidence is increasing worldwide. However, there are currently no effective treatments or medications available for individuals with CD. Therefore, novel therapeutic strategies are urgently needed. The bioactive compounds and targets associated with compounds of Qinghua Xiaoyong Formula (QHXYF) were examined using The Traditional Chinese Medicine Systems Pharmacology database, and 5 disease target databases were also used to identify CD-related disease targets. A total of 166 overlapping targets were identified from QHXYF-related and CD-related disease targets and they were found to be enriched in oxidative stress-related pathways and the PI3K/AKT signaling pathway. Molecular docking was then used to predict how the bioactive compounds would bind to the hub targets. It was found that quercetin could be the core bioactive compound and had good binding affinity to the top 5 hub targets. Finally, animal experiments were performed to further validate the findings, and the results revealed that QHXYF or quercetin inhibited 2,4,6-trinitrobenzenesulfonic acid-induced inflammation and oxidative stress processes by inhibiting the PI3K/AKT pathway, thereby improving CD symptoms. These findings suggest that QHXYF and quercetin may be potential novel treatments for CD.

• The Korea Journal of Herbology
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• v.38 no.6
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• pp.29-44
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• 2023

Objectives : This study was planned to evaluate the therapeutic effectiveness and possible underlying mechanism of TPE (Tetrapanax papyrifer stem(inner part of the stem Extract) and AQE (Akebiae quinata stem Extract) on osteoarthritis. Methods : Osteoarthritis models were induced through intra-articular injection of MIA (monosodium iodoacetate) 50 μL with 80 mg/ml in rats. Excluding the normal group, Osteoarthritis-induced rats were divided into 4 groups (Control, INDO, TPE, AQE). The drug concentrations were indomethacin 5 mg/kg, TPE 200 mg/kg, and AQE 200 mg/kg, and were orally administered once a day for a couple of weeks. After drug supplementation, the effects of TPE and AQE were measured with serum diagnosis, western blotting, and histopathological staining. Results : It was found that the DPPH and ABTS free radical erasure ability of AQE was better than that of TPE. AQE administration improved rear limb overload and it led to relieving pain. Both PTE and AQE significantly reduced the expression of inflammatory mediators COX-2, iNOS, and inflammatory cytokine IL-1β and IL-6 by inhibiting the phosphorylation of IκBα and deactivating the pathway of NF-κBp65. On the other hand, TNF-α was significantly reduced only by administration of AQE. In addition, histopathological analysis showed that the administration of AQE compared to PTE suppressed cartilage degeneration and effectively suppressed damage to proteoglycan, a component of ECM. Conclusion : Reviewing these experimental results, TPE and AQE possessed the effect of delaying the progress of osteoarthritis and protecting cartilage. In addition, the results of this study show that AQE has a better cartilage protection effect than TPE.

• The Korea Journal of Herbology
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• v.38 no.6
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• pp.73-91
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• 2023

Objectives : This study used a network pharmacology approach to elucidate the efficacy and molecular mechanisms of Daehwangmokdanpitang (DHMDPT) on Psoriasis. Methods : Using OASIS databases and PubChem database, compounds of DHMDPT and their target genes were collected. The putative target genes of DHMDPT and known target genes of psoriasis were compared and found the correlation. Then, the network was constructed using Cytoscape 3.10.1. The key target genes were screened by Analyzer network and their functional enrichment analysis was conducted based on the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms. Results : The result showed that total 30 compounds and 439 related genes were gathered from DHMDPT. 264 genes were interacted with psoriasis gene set, suggesting that the effects of DHMDPT are closely related to psoriasis. Based on GO enrichment analysis and KEGG pathways, 'Binding', 'Cytokine Activity', 'Receptor Ligand Activity' 'HIF-1 signaling pathway', 'IL-17 signaling pathway', 'Toll-like receptor signaling pathway', and 'TNF signaling pathway' were predicted as functional pathways of 16 key target genes of DHMDPT on psoriasis. Among the target genes, IL6, IL1B, TNF, AKT1 showed high correlation with the results of KEGG pathways. Additionally, Emodin, Acetovanillone, Gallic acid, and Ferulic acid showed a high relevance with key genes and their mechanisms. Conclusion : Through a network pharmacological method, DHMDPT was predicted to have high relevance with psoriasis. This study could be used as a basis for studying therapeutic effects of DHMDPT on psoriasis.

• BMB Reports
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• v.56 no.11
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• pp.600-605
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• 2023

Intrahepatic cholangiocarcinoma (ICC) is a bile duct cancer and a rare malignant tumor with a poor prognosis owing to the lack of an early diagnosis and resistance to conventional chemotherapy. A combination of gemcitabine and cisplatin is the typically attempted first-line treatment approach. However, the underlying mechanism of resistance to chemotherapy is poorly understood. We addressed this by studying dynamics in the human ICC SCK cell line. Here, we report that the regulation of glucose and glutamine metabolism was a key factor in overcoming cisplatin resistance in SCK cells. RNA sequencing analysis revealed a high enrichment cell cycle-related gene set score in cisplatin-resistant SCK (SCK-R) cells compared to parental SCK (SCK WT) cells. Cell cycle progression correlates with increased nutrient requirement and cancer proliferation or metastasis. Commonly, cancer cells are dependent upon glucose and glutamine availability for survival and proliferation. Indeed, we observed the increased expression of GLUT (glucose transporter), ASCT2 (glutamine transporter), and cancer progression markers in SCK-R cells. Thus, we inhibited enhanced metabolic reprogramming in SCK-R cells through nutrient starvation. SCK-R cells were sensitized to cisplatin, especially under glucose starvation. Glutaminase-1 (GLS1), which is a mitochondrial enzyme involved in tumorigenesis and progression in cancer cells, was upregulated in SCK-R cells. Targeting GLS1 with the GLS1 inhibitor CB-839 (telaglenastat) effectively reduced the expression of cancer progression markers. Taken together, our study results suggest that a combination of GLUT inhibition, which mimics glucose starvation, and GLS1 inhibition could be a therapeutic strategy to increase the chemosensitivity of ICC.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.629-639
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• 2023

Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also downregulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.