• BMB Reports
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• v.52 no.10
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• pp.595-600
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• 2019

Cardiac fibrosis is a common feature in chronic hypertension patients with advanced heart failure, and endothelial-to-mesenchymal transition (EndMT) is known to promote Angiotensin II (Ang II)-mediated cardiac fibrosis. Previous studies have suggested a potential role for the transcription factor, ETS-1, in Ang II-mediated cardiac remodeling, however the mechanism are not well defined. In this study, we found that mice with endothelial Ets-1 deletion showed reduced cardiac fibrosis and hypertrophy following Ang II infusion. The reduced cardiac fibrosis was accompanied by decreased expression of fibrotic matrix genes, reduced EndMT with decreased Snail, Slug, Twist, and ZEB1 expression, as well as reduced cardiac hypertrophy and expression of hypertrophy-associated genes was observed. In vitro studies using cultured H5V cells further confirmed that ETS-1 knockdown inhibited $TGF-{\beta}1$-induced EndMT. This study revealed that deletion of endothelial Ets-1 attenuated Ang II-induced cardiac fibrosis via inhibition of EndMT, indicating an important ETS-1 function in mediating EndMT. Inhibition of ETS-1 could be a potential therapeutic strategy for treatment of heart failure secondary to chronic hypertension.

• Journal of Ginseng Research
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• v.39 no.1
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• pp.46-53
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• 2015

Background: Glucocorticoids (GCs) are commonly used in many chemotherapeutic protocols and play an important role in the normal regulation of bone remodeling. However, the prolonged use of GCs results in osteoporosis, which is partially due to apoptosis of osteoblasts and osteocytes. In this study, effects of Korean Red Ginseng (KRG) on GC-treated murine osteoblastic MC3T3-E1 cells and a GC-induced osteoporosis mouse model were investigated. Methods: MC3T3-E1 cells were exposed to dexamethasone (Dex) with or without KRG and cell viability was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Realtime polymerase chain reaction was performed to evaluate the apoptotic gene expression; osteogenic gene expression and alkaline phosphatase (ALP) activity were also measured. Western blotting was performed to evaluate the mitogen-activated protein kinase (MAPK) proteins. A GC-induced osteoporosis animal model was used for in vivo study. Results and conclusion: The MTT assay revealed that Korean Red Ginseng (KRG) prevents loss of cell viability caused by Dex-induced apoptosis in MC3T3E1 cells. Real-time polymerase chain reaction data showed that groups treated with both Dex and KRG exhibited lower mRNA levels of caspase-3 and -9, whereas the mRNA levels of Bcl2, IAPs, and XIAP increased. Moreover, groups treated with both Dex and KRG demonstrated increased mRNA levels of ALP, RUNX2, and bone morphogenic proteins as well as increased ALP activity in MC3T3-E1 cells, compared to cells treated with Dex only. In addition, KRG increased protein kinase B (AKT) phosphorylation and decreased c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, microcomputed tomography analysis of the femurs showed that GC implantation caused trabecular bone loss. However, a significant reduction of bone loss was observed in the KRG-treated group. These results suggest that the molecular mechanism of KRG in the GC-induced apoptosis may lead to the development of therapeutic strategies to prevent and/or delay osteoporosis.

• Korean Journal of Veterinary Service
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• v.44 no.3
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• pp.169-174
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• 2021

Mastitis is an inflammatory condition of the mammary gland, most often caused by bacterial infections, resulting in significant economic losses to the dairy industry. Antimicrobial resistance has been of great concern because of the extensive clinical use of antibiotics. For this reason, the development of new compounds as an alternative treatment to bovine mastitis is needed. Bee venom has been widely used as an oriental treatment for several inflammatory diseases and bacterial infections. The aim of the present study was to evaluate the antimicrobial activity of bee venom on bacteria isolated from bovine mastitis. A total of 107 isolates from bovine mastitic milk samples collected in 2019 and 2020 in Jeonbuk province. All bacterial isolates were tested for susceptibility to bee venom of the honey bee (Apis mellifera). In order to obtain comprehensive antibacterial activities of the bee venom, we measured the minimal inhibitory concentration (MIC) of the bee venom against bacterial strains. Bee venom showed significant inhibition of bacterial growth of Gram-negative bacteria Citrobacter spp., Escherchia coli, Klebsiella spp., Pseudomonas spp., Serratia spp. and Raoultella with MIC values of 96, 81, 72, 230, and 85 ㎍/mL, respectively, and Gram-positive bacterial Enterococcus spp., Staphylococcus spp. and Streptococcus spp. with MIC values of 29, 21 and 16 ㎍/mL, respectively. The results indicated that the MIC values were different depending on the bacterial strains, and those of Gram-positive bacteria were lower than those of Gram-negative bacteria for bee venom. These findings suggested that bee venom could be an effective antimicrobial treatment for bovine mastitis; however, further research is necessary to evaluate the mechanism underlying the antimicrobial action, its effectiveness/safety in vivo and effective application for therapeutic use.

• Journal of Microbiology and Biotechnology
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• v.31 no.4
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• pp.540-549
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• 2021

The Wnt/β-catenin signaling pathway is involved in breast cancer and Myxococcus fulvus KYC4048 is a myxobacterial strain that can produce a variety of bioactive secondary metabolites. Although a previous study revealed that KYC4048 metabolites exhibit anti-proliferative effects on breast cancer, the biochemical mechanism involved in their effects remains unclear. In the present study, KYC4048 metabolites were separated into polar and non-polar (ethyl acetate and n-hexane) fractions via liquid-liquid extraction. The effects of these polar and non-polar KYC4048 metabolites on the viability of breast cancer cells were then determined by MTT assay. Expression levels of Wnt/β-catenin pathway proteins were determined by Western blot analysis. Cell cycle and apoptosis were measured via fluorescence-activated cell sorting (FACS). The results revealed that non-polar KYC4048 metabolites induced cell death of breast cancer cells and decreased expression levels of WNT2B, β-catenin, and Wnt target genes (c-Myc and cyclin D1). Moreover, the n-hexane fraction of non-polar KYC4048 metabolites was found most effective in inducing apoptosis, necrosis, and cell cycle arrest, leading us to conclude that it can induce apoptosis of breast cancer cells through the Wnt/β-catenin pathway. These findings provide evidence that the n-hexane fraction of non-polar KYC4048 metabolites can be developed as a potential therapeutic agent for breast cancer via inhibition of the Wnt/β-catenin pathway.

• Korean Journal of Family Social Work
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• no.55
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• pp.91-128
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• 2017

The purpose of this study is to develop an effective intervention strategy for marriage migrant woman in family therapy. For this purpose, we collected counseling cases of professional counselors who successfully completed counseling and attempted the qualitative analysis of treatment intervention strategies and effects. The results of the study were obtained by dividing the meaning units in the immigrant woman's statements made during the counseling process composed of a total of 6 sessions. The counselors were analyzed to have tried the following intervention strategies. They attempted the following six strategies: Helping emotional differentiation by searching for unresolved emotional problems, dealing with undifferentiation due to family projection process and love triangle, dealing with multi-generational transfer process of the original family relationship patterns and coping mechanism, shedding lihgt on ineffectiveness of inconsistent communication due to emotional oppression applying a communication model of MRI, switching client's awareness through reorganization, suggesting a way of communication that leads to real self. Such counselors' attempts resulted in positive changes and treatment effects were found to include first, cognitive insights and motivation for change, second, improved communication skills and third, anxiety reduction and self-differentiation. Due to their husbands' refusal to participate in counseling, marriage migrant women often get involved in counseling alone, so they tend to worry that the effectiveness of family therapy may be low but it was found that the proper intervention of the counselor could improve the ability of the wife to resolve conflicts, which would be a great help in solving problems such as family violence and this study is meaningful in that it provided the appropriate therapeutic intervention strategies needed.

• BMB Reports
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• v.52 no.5
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• pp.318-323
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• 2019

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that present immunosuppressive effects in experimental and clinical trials targeting various rare diseases including inflammatory bowel disease (IBD). In addition, recent studies have reported tryptophanyl-tRNA synthetase (WRS) possesses uncanonical roles such as angiostatic and anti-inflammatory effects. However, little is known about the function of WRS in MSC-based therapy. In this study, we investigated if a novel factor, WRS, secreted from MSCs has a role in amelioration of IBD symptoms and determined a specific mechanism underlying MSC therapy. Experimental colitis was induced by administration of 3% DSS solution to 8-week-old mice and human umbilical cord blood-derived MSCs (hUCB-MSCs) were injected intraperitoneally. Secretion of WRS from hUCB-MSCs and direct effect of WRS on isolated $CD4^+$ T cells was determined via in vitro experiments and hUCB-MSCs showed significant therapeutic rescue against experimental colitis. Importantly, WRS level in serum of colitis induced mice decreased and recovered by administration of MSCs. Through in vitro examination, WRS expression of hUCB-MSCs increased when cells were treated with interferon-${\gamma}$ ($IFN-{\gamma}$). WRS was evaluated and revealed to have a role in inhibiting activated T cells by inducing apoptosis. In summary, $IFN-{\gamma}$-mediated secretion of WRS from MSCs has a role in suppressive effect on excessive inflammation and disease progression of IBD and brings new highlights in the immunomodulatory potency of hUCB-MSCs.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.2
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• pp.221-234
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• 2019

Cancer is genetically, metabolically and infectiously induced life threatening disorder showing aggressive growing pattern with invasive tendency. In order to prevent this global menace from jeopardizing human life, enormous studies on carcinogenesis and treatment for chemotherapy resistance have been intensively researched. Hinokitiol (${\beta}$-thujaplicin) extracted from heart wood of cupressaceous is a well-known bioactive compound demonstrating anti-inflammation, anti-bacteria and anti-cancer effects on several cancer types via apoptosis and autophagy. This study proposed that hinokitiol activates transcription factor EB (TFEB) nuclear translocation for autophagy and lysosomal biogenesis regardless of nutrient condition in cancer cells. Mitophagy and ${\beta}$-catenin translocation into the nucleus under treatment of hinokitiol on non-small cell lung cancer (NSCLC) cells and HeLa cells were investigated. Hinokitiol exerted cytotoxicity on HeLa and HCC827 cells; moreover, artificially induced autophagy by overexpression of TFEB granted imperfect sustainability onto HeLa cells. Taken together, hinokitiol is the prominent autophagy inducer and activator of TFEB nuclear translocation. Alternative cancer therapy via autophagy is pros and cons since the autophagy in cancer cells is related to prevention and survival mechanism depending on nutrition. To avoid paradox of autophagy in cancer therapy, fine-tuned regulation and application of hinokitiol in due course for successful suppressing cancer cells are recommended.

• Korean Journal of Plant Resources
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• v.32 no.2
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• pp.109-115
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• 2019

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of branches from Taxillus yadoriki parasitic to Neolitsea sericea (TN-NS-B) against human lung cancer cells, A549. TY-NS-B dose-dependently suppressed the growth of A549 cells. TY-NS-B decreased ${\beta}$-catenin protein level, but not mRNA level in A549 cells. The downregulation of ${\beta}$-catenin protein level by TY-NS-B was attenuated in the presence of MG132. Although TY-NS-B phosphorylated ${\beta}$-catenin protein, the inhibition of $GSK3{\beta}$ by LiCl did not blocked the reduction of ${\beta}$-catenin by TY-NS-B. In addition, TY-NS-B decreased ${\beta}$-catenin protein in A549 cells transfected with Flag-tagged wild type ${\beta}$-catenin or Flag-tagged S33/S37/T41 mutant ${\beta}$-catenin construct. Our results suggested that TN-NS-B may downregulate ${\beta}$-catenin protein level independent on $GSK3{\beta}$-induced ${\beta}$-catenin phosphorylation. Based on these findings, TY-NS-B may be a potential candidate for the development of chemopreventive or therapeutic agents for human lung cancer.

• Journal of Plant Biotechnology
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• v.48 no.2
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• pp.106-114
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• 2021

We evaluated the anti-cancer activity against human prostate cancer cells and the associated molecular mechanism of extracts from the branches of Rhamnus yoshinoi (RYB). Treatment with RYB suppressed viability of human prostate cancer cells (PC-3) and decreased protein levels of both β-catenin and T-cell factor 4 (TCF4). This was reflected in reduced TCF4 mRNA, but not decreased β-catenin mRNA. PC-3 cells were pretreated with the proteosome inhibitor MG132 before treatment with RYB, which blocked RYB-mediated down regulation of β-catenin in PC-3 cells, thus confirming that RYB promotes the proteasomal degradation of β-catenin. RYB induced β-catenin phosphorylation, and GSK-3β inhibition by LiCl blocked the phosphorylation and proteasomal degradation of β-catenin by RYB. These results suggest that GSK-3β may be an important upstream kinase for RYB-mediated regulation of β-catenin. Finally, GC/MS analysis of RYB identified 18 compounds. Based on these findings, RYB shows potential for development as a therapeutic agent for prostate cancer.

• Journal of Korean Medicine Rehabilitation
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• v.31 no.1
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• pp.17-32
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• 2021

Objectives The present study was designed to find out the therapeutic effects and possible underlying mechanism of Buja-tang, a herbal complex formula on experimental monosodium iodoacetate (MIA)-induced osteoarthritis. Methods Osteoarthritis models were created via intra-joint injection of MIA (50 μL with 80 mg/mL) in rats. Rats were divided into five groups and each group consisted of seven. Normal group was not injected MIA and did a normal diet. Control group injected MIA and received distilled water. Indo injected MIA and oral administration of 5 mg/kg of indomethacin. BJTL injected MIA and oral administration of 100 mg/kg of Buja-tang. BJTH injected MIA and oral administration of 200 mg/kg of Buja-tang. We analyzed weight-bearing ability of hind paws, oxidative stress related factor, antioxidant protein, inflammatory protein, inflammatory messenger and cytokine in joint tissue. Pathological observation of knee cartilage tissue structures was also performed with hematoxylin & eosin and safranin-O chromosomes. Results Weight-bearing ability of hind paws showed a tendency to reduce pain. The incidence of nicotinamide adenine dinucleotide phosphate oxidase and p22phox in articular tissue was significantly reduced, and the incidence of nuclear factor-erythroid 2-related factor 2 and heme oxygenase-1 and superoxide dismutases was significantly increased. The incidence of phosphorylated inhibitor of κBα, nuclear factor-kappa B p65, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β decreased significantly. In pathological observation, cartilage tissue damaged by MIAs in biopsy has significantly recovered from Buja-tang administration. Conclusions Buja-tang has anti-inflammation, antioxidation and pain relief effects. So this is thought to inhibit the progress of osteoarthritis in rat caused by the MIA.