• Journal of Radiation Industry
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• v.6 no.3
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• pp.223-229
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• 2012

In this study, we investigated the biological damage and stress responses induced by ion beam (proton beam) irradiation as a basis for the development of protective measures against space radiation. We examined the biological effects of proton beam produced by MC-50 cyclotron at KIRAMS on the cultured cells and mice. The proton beam energy used in this study was 34.9 MeV and the absorption dose rate for cells and mice were $0.509Gy\;sec^{-1}$ and $0.65Gy\;sec^{-1}$, respectively. The cell survival rates measured by plating efficiency showed the different sensitivity and dose-relationship between CHO cells and Balb/3T3 cells. HGPRT gene mutation frequency in Balb/3T3 was $15{\times}10^{-6}Gy^{-1}$, which was similar to the reported value of X-ray. When stress signaling proteins were examined in Balb/3T3 cells, $I{\kappa}B-{\alpha}$ decreased markedly whereas p53, phospho-p53, and Rb increased after proton beam irradiation, which implied that the stress signaling pathways were activated by proton beam irradiation. In addition, cellular senescence was induced in IMR-90 cells. In the experiments with C57BL/6 mouse, the immune cells (white blood cells, lymphocytes) in the peripheral blood were greatly reduced following proton beam irradiation whereas red blood cells and platelets showed relatively little change. These results can be utilized as basic data for studying the biological effects of proton beam using MC-50 cyclotron with respect to proton therapy research as well as space radiation research.

• Molecules and Cells
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• v.42 no.11
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• pp.755-762
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• 2019

Despite decades of research into colorectal cancer (CRC), there is an ongoing need for treatments that are more effective and safer than those currently available. Lactic acid bacteria (LAB) show beneficial effects in the context of several diseases, including CRC, and are generally regarded as safe. Here, we isolated a Lactobacillus rhamnosus (LR)-derived therapeutic protein, p8, which suppressed CRC proliferation. We found that p8 translocated specifically to the cytosol of DLD-1 cells. Moreover, p8 down-regulated expression of Cyclin B1 and Cdk1, both of which are required for cell cycle progression. We confirmed that p8 exerted strong anti-proliferative activity in a mouse CRC xenograft model. Intraperitoneal injection of recombinant p8 (r-p8) led to a significant reduction (up to 59%) in tumor mass when compared with controls. In recent years, bacterial drug delivery systems (DDSs) have proven to be effective therapeutic agents for acute colitis. Therefore, we aimed to use such systems, particularly LAB, to generate the valuable therapeutic proteins to treat CRC. To this end, we developed a gene expression cassette capable of inducing secretion of large amounts of p8 protein from Pediococcus pentosaceus SL4 (PP). We then confirmed that this protein (PP-p8) exerted anti-proliferative activity in a mouse CRC xenograft model. Oral administration of PP-p8 DDS led to a marked reduction in tumor mass (up to 64%) compared with controls. The PP-p8 DDS using LAB described herein has advantages over other therapeutics; these advantages include improved safety (the protein is a probiotic), cost-free purification, and specific targeting of CRC cells.

• Molecules and Cells
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• v.44 no.10
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• pp.710-722
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• 2021

Hypoxia, or low oxygen tension, is a hallmark of the tumor microenvironment. The hypoxia-inducible factor-1α (HIF-1α) subunit plays a critical role in the adaptive cellular response of hypoxic tumor cells to low oxygen tension by activating gene-expression programs that control cancer cell metabolism, angiogenesis, and therapy resistance. Phosphorylation is involved in the stabilization and regulation of HIF-1α transcriptional activity. HIF-1α is activated by several factors, including the mitogen-activated protein kinase (MAPK) superfamily. MAPK phosphatase 3 (MKP-3) is a cytoplasmic dual-specificity phosphatase specific for extracellular signal-regulated kinase 1/2 (Erk1/2). Recent evidence indicates that hypoxia increases the endogenous levels of both MKP-3 mRNA and protein. However, its role in the response of cells to hypoxia is poorly understood. Herein, we demonstrated that small-interfering RNA (siRNA)-mediated knockdown of MKP-3 enhanced HIF-1α (not HIF-2α) levels. Conversely, MKP-3 overexpression suppressed HIF-1α (not HIF-2α) levels, as well as the expression levels of hypoxia-responsive genes (LDHA, CA9, GLUT-1, and VEGF), in hypoxic colon cancer cells. These findings indicated that MKP-3, induced by HIF-1α in hypoxia, negatively regulates HIF-1α protein levels and hypoxia-responsive genes. However, we also found that long-term hypoxia (>12 h) induced proteasomal degradation of MKP-3 in a lactic acid-dependent manner. Taken together, MKP-3 expression is modulated by the hypoxic conditions prevailing in colon cancer, and plays a role in cellular adaptation to tumor hypoxia and tumor progression. Thus, MKP-3 may serve as a potential therapeutic target for colon cancer treatment.

• The Korean Journal of Food And Nutrition
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• v.34 no.2
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• pp.196-206
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• 2021

The main purpose of this study was to examine the correlation between the consumption of red ginseng-based 'SSR' for 30 days and the reduction in human fatigue, blood component changes, and immune cell activity in 35 human subjects. 'SSR' is composed of zinc oxide, folic acid, and D-α-tocopherol with red ginseng as the main component. According to the protocol criteria of the study, 35 subjects who understood the purpose of the study and signed an informed consent form were selected. The fatigue survey was conducted through a questionnaire, and after taking 'SSR', a decreased tendency of physical, mental, and neurosensory fatigue was observed. In hematological analysis, no significant changes were observed in the levels of WBC, RBC, and hemoglobin; however, AST (SGOT) and ALT (SGPT) levels were statistically significantly decreased. In immunological analysis, it was observed that the proliferative effect of T cells (CD3+CD4+) was greater than that of NK cells (CD16+CD56+). The collected data were subjected to t-test analysis using the SPSS 25.0 statistical program. The result from this study proposes that 'SSR' can be used as a functional food material as it reduces human fatigue and enhances immune function.

• Journal of Lipid and Atherosclerosis
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• v.7 no.2
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• pp.122-154
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• 2018

Familial hypercholesterolemia (FH) is typically associated with single gene mutation that is inherited by autosomal dominant manner. Due to high cardiovascular risk, aggressive discovery, diagnosis, and treatment of FH are critical. Although FH is being increasingly spotlighted, we do not have sufficient data on Korean patients with FH. Here, we present the content of symposium of the Education Committee, Korean Society of Lipid and Atherosclerosis held in May 2018: 1) epidemiology, clinical diagnosis, Korean FH data, and regulation in Korea; 2) genes associated with FH, sequencing process in suspicious proband, cascade screening, and difficulty in genetic diagnosis in FH; 3) the importance of lipid-lowering therapy in FH, conventional and novel therapeutics for FH; 4) diagnosis of FH in children and adolescence, screening, and treatment of FH in children and adolescence; 5) history of FH studies in Korea, the structure and current status of FH registry of Korean Society of Lipid and Atherosclerosis; and 6) difficulty in diagnosis of heterozygous and homozygous FH, drug intolerance and achievement of treatment target. Discussion between speakers and panels were also added. We hope that this article is helpful for understanding FH and future studies performed in Korea.

• Genomics & Informatics
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• v.16 no.4
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• pp.19.1-19.11
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• 2018

MicroRNAs (miRNAs), small non-coding RNAs, have been implicated in various diseases and cellular functions as microregulators of gene expression. Although the history of miRNA investigation in autoimmune $Sj{\ddot{o}}gren^{\prime}s$ syndrome (SjS) is fairly short, a substantial amount of data has already been accumulated. These findings clearly indicate potential clinical implications of miRNAs, such as autoantigen expression and autoantibody production, viral miRNAs regulating the calcium signaling pathway, and aberrant immune cell regulation and cytokine production. Research endeavors in the field are currently underway to select disease-specific diagnostic and prognostic biomarkers by utilizing different types of tissues or biological specimens of SjS patients. Various techniques for miRNA analysis with different stringencies have been applied, with the most recent one being next-generation sequencing. This review compiles and highlights differentially-expressed miRNAs in various samples collected from SjS patients and their potential implications in the pathogenesis of SjS. To facilitate the development of miRNA-targeted personalized therapy in the future, we urge more follow-up studies that confirm these findings and elucidate the immunopathological roles of differentially-expressed miRNAs. Furthermore, improved diagnostic criteria for the disease itself will minimize sampling errors in patient recruitment, preventing the generation of inconsistent data.

• The Journal of Internal Korean Medicine
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• v.40 no.1
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• pp.70-88
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• 2019

Objective: This study investigated the trends in pancreatic cancer research on Korean medicine in order to establish a direction for further study. Methods: Pancreatic cancer research on Korean medicine was reviewed using databases such as OASIS, KoreanTK, KISS, RISS, KISTI, and NDSL. The search terms were "pancreatic cancer" "Korean medicine," and "herbal medicine." There was no restriction on publication dates, and the reviewed studies were analyzed according to the type of research. Results: Nineteen studies were reviewed. The numbers and types of research were as follows: 9 clinical studies including case reports, 2 review studies, and 8 in vitro studies; there was no in vivo study. Among the clinical research were 3 descriptive studies and 6 case reports. The baseline characteristics and quality of life of pancreatic cancer patients were analyzed in the descriptive studies. In the case reports, interventions such as herbal medicine, pharmacopuncture, and acupuncture were used. Research articles on the review of pancreatic cancer were titled "Preliminary Study for Development of Korean Medicine Clinical Practice Guideline for Pancreatic Cancer" and "Systemic Review on the Tumor Dormancy Therapy." Cell lines such as PANC-1, MIA PaCa-2, and AsPC-1 were used for in vitro studies. These studies have reported decreased cell viability, induced apoptosis, and changes in cancer-related gene expression. Conclusion: Through this review, we found that using Korean medicine for treating pancreatic cancer is applicable. However, due to overall limited the number of study, the benefit of Korean medicine for pancreatic cancer may be substantiated to a limited degree. Better methodological quality and large controlled trials are expected to further quantify the therapeutic effect of Korean medicine.

• Journal of Pharmacopuncture
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• v.22 no.2
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• pp.102-108
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• 2019

Objectives: Esophageal squamous cell carcinoma (ESCC) is considered as a deadly medical condition that affects a growing number of people worldwide. Targeted therapy of ESCC has been suggested recently and required extensive research. With cyclin D1 as a therapeutic target, the present study aimed at evaluating the anticancer effects of doxorubicin (Dox) or Hypericum perforatum L. (HP) extract encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on the ESCC cell line KYSE30. Methods: Nanoparticles were prepared using double emulsion method. Cytotoxicity assay was carried out to measure the anti-proliferation activity of Dox-loaded (Dox NPs) and HP-loaded nanoparticles (HP NPs) against both cancer and normal cell lines. The mRNA gene expression of cyclin D1 was evaluated to validate the cytotoxicity studies at molecular level. Results: Free drugs and nanoparticles significantly inhibited KYSE30 cells by 55-73% and slightly affected normal cells up to 29%. The IC50 of Dox NPs and HP NPs was ~ 0.04-0.06 mg/mL and ~ 0.6-0.7 mg/mL, respectively. Significant decrease occurred in cyclin D1 expression by Dox NPs and HP NPs (P < 0.05). Exposure of KYSE-30 cells to combined treatments including both Dox and HP extract significantly increased the level of cyclin D1 expression as compared to those with individual treatments (P < 0.05). Conclusion: Dox NPs and HP NPs can successfully and specifically target ESCC cells through downregulation of cyclin D1. The simultaneous use of Dox and HP extract should be avoided for the treatment of ESCC.

• Biomaterials Research
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• v.22 no.4
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• pp.337-345
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• 2018

Background: Human mesenchymal stem cells (hMSCs) are, due to their pluripotency, useful sources of cells for stem cell therapy and tissue regeneration. The phenotypes of hMSCs are strongly influenced by their microenvironment, in particular the extracellular matrix (ECM), the composition and structure of which are important in regulating stem cell fate. In reciprocal manner, the properties of ECM are remodeled by the hMSCs, but the mechanism involved in ECM remodeling by hMSCs under topographical stimulus is unclear. In this study, we therefore examined the effect of nanotopography on the expression of ECM proteins by hMSCs by analyzing the quantity and structure of the ECM on a nanogrooved surface. Methods: To develop the nanoengineered, hMSC-derived ECM, we fabricated the nanogrooves on a coverglass using a UV-curable polyurethane acrylate (PUA). Then, hMSCs were cultivated on the nanogrooves, and the cells at the full confluency were decellularized. To analyze the effect of nanotopography on the hMSCs, the hMSCs were re-seeded on the nanoengineered, hMSC-derived ECM. Results: hMSCs cultured within the nano-engineered hMSC-derived ECM sheet showed a different pattern of expression of ECM proteins from those cultured on ECM-free, nanogrooved surface. Moreover, hMSCs on the nano-engineered ECM sheet had a shorter vinculin length and were less well-aligned than those on the other surface. In addition, the expression pattern of ECM-related genes by hMSCs on the nanoengineered ECM sheet was altered. Interestingly, the expression of genes for osteogenesis-related ECM proteins was downregulated, while that of genes for chondrogenesis-related ECM proteins was upregulated, on the nanoengineered ECM sheet. Conclusions: The nanoengineered ECM influenced the phenotypic features of hMSCs, and that hMSCs can remodel their ECM microenvironment in the presence of a nanostructured ECM to guide differentiation into a specific lineage.

• Journal of Microbiology and Biotechnology
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• v.31 no.2
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• pp.197-206
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• 2021

microRNA-361-3p (miR-361-3p) is involved in the carcinogenesis of oral cancer and pancreatic catheter adenocarcinoma, and has anti-carcinogenic effects on non-small cell lung cancer (NSCLC). However, its effect on multiple myeloma (MM) is less reported. Here, we found that upregulating the expression of miR-361-3p inhibited MM cell viability and promoted MM apoptosis. We measured expressions of tumor necrosis factor receptor-associated factor 6 (TRAF6) and miR-361-3p in MM cells and detected the viability, colony formation rate, and apoptosis of MM cells. In addition, we measured expressions of apoptosis-related genes Bcl-2, Bax, and Cleaved caspase-3 (C caspase-3). The binding site between miR-361-3p and TRAF6 was predicted by TargetScan. Our results showed that miR-361-3p was low expressed in the plasma of MM patients and cell lines, while its overexpression inhibited viability and colony formation of MM cells and increased the cell apoptosis. Furthermore, TRAF6, which was predicted to be a target gene of miR-361-3p, was high-expressed in the plasma of patients and cell lines with MM. Rescue experiments demonstrated that the effect of TRAF6 on MM cells was opposite to that of miR-361-3p. Upregulation of miR-361-3p induced apoptosis and inhibited the proliferation of MM cells through targeting TRAF6, suggesting that miR-361-3p might be a potential target for MM therapy.