• Proceedings of the PSK Conference
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• 2003.10b
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• pp.248.1-248.1
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• 2003

Keloids are characterized by abnormal proliferation of fibroblasts and overproduction of collagen. Recently, it is reported that transforming growth factor beta (TGFb) and its signaling molecule, SMAD3 are related to the mitogenic effect of fibroblasts and a stimulatory factor for collagen synthesis. Cationic SLN was developed to improve the complex formation of DNA/SLN and enhance the uptake efficiency to cells. SLN was formulated by DC-Chol, DOPE, trimyristin as a solid core and other surfactant. The physical properties of the SLN and the ATS-SLN complex were characterized. (omitted)

• Biomedical Science Letters
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• v.28 no.4
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• pp.276-283
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• 2022

Saccharina japonica (SJ), a brown algae, exerts various pharmacological effects, including anti-oxidant, immunemodulating and anti-cancer properties. This study aimed to determine the pharmacological mechanism of SJ on atopic dermatitis in vivo and in vitro. We investigated the pharmacological effects of SJ on 2, 4-dinitrochlrobenzene (DNCB)- induced atopic dermatitis clinical symptoms in mice. Additionally, we evaluated the effects of SJ on the inflammatory cytokine production and nuclear factor-κB (NF-κB) activation in HaCaT cells. The findings of this study demonstrated that SJ reduced the clinical symptoms of atopic dermatitis, such as skin dryness, erythema and eczematous, and serum histamine and IgE level in DNCB-induced atopic dermatitis model. Additionally, SJ inhibited the NF-κB activation in atopic dermatitis-like skin lesion and HaCaT cells. Collectively, this result suggests that SJ could be used as a therapeutic agent for skin inflammation, including atopic dermatitis.

• Molecules and Cells
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• v.46 no.3
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• pp.133-141
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• 2023

Transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. NRF2 induces expression of detoxification and antioxidant enzymes and suppresses inductions of pro-inflammatory cytokine genes. KEAP1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of CULLIN 3 (CUL3)-based E3 ubiquitin ligase. KEAP1 regulates the activity of NRF2 and acts as a sensor for oxidative and electrophilic stresses. NRF2 has been found to be activated in many types of cancers with poor prognosis. Therapeutic strategies to control NRF2-overeactivated cancers have been considered not only by targeting cancer cells with NRF2 inhibitors or NRF2 synthetic lethal chemicals, but also by targeting host defense with NRF2 inducers. Understanding precise molecular mechanisms how the KEAP1-NRF2 system senses and regulates the cellular response is critical to overcome intractable NRF2-activated cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4609-4614
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• 2016

Purpose: To evaluate the therapeutic effects of copper reduction on angiogenesis-related factors in patients with glioblastoma multiforme treated by gamma knife radiosurgery. Materials and Methods: In the present block randomized, placebo-controlled trial, fifty eligible patients with a diagnosis of glioblastoma multiforme who were candidates for gamma knife radiosurgery were randomly assigned into two groups to receive daily either 1gr penicillamine and a low copper diet or placebo for three months. The intervention started on the same day as gamma knife radiosurgery. Serum interleukin-6 (IL-6), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), vascular endothelial growth factor (VEGF) and copper levels were measured at baseline and after the intervention. The serum copper level was used as the final index of compliance with the diet. In order to control probable side effects of intervention, laboratory tests were conducted at the beginning, middle and end of the study. Results: The patients had a mean age and Karnofsky Performance Scale of 43.7 years and 75 respectively. Mean serum copper levels were significantly reduced in intervention group. Mean survival time was 18.5 months in intervention group vs. 14.9 in placebo group. VEGF and IL-6 levels in the intervention group were also significantly reduced compared to the placebo group and $TNF-{\alpha}$ increased less. Conclusions: It seems that reducing the level of copper in the diet and dosing with penicillamine leads to decline of angiogenesis-related factors such as VEGF, IL-6 and $TNF-{\alpha}$. Approaches targeting angiogenesis may improve survival and can be used as a future therapeutic strategy.

• Journal of Microbiology and Biotechnology
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• v.23 no.9
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• pp.1327-1338
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• 2013

The humanized anti-hepatocyte growth factor (HGF) monoclonal antibody (mAb) YYB-101 is a promising therapeutic candidate for treating various cancers. In this study, we developed a bioprocess for large-scale production of YYB-101 and evaluated its therapeutic potential for tumor treatment using a xenograft mouse model. By screening diverse chemically defined basal media formulations and by assessing the effects of various feed supplements and feeding schedules on cell growth and antibody production, we established an optimal medium and feeding method to produce 757 mg/l of YYB-101 in flask cultures, representing a 7.5-fold increase in titer compared with that obtained under non-optimized conditions. The optimal dissolved oxygen concentration for antibody production was 70% $pO_2$. A pH shift from 7.2 to 7.0, rather than controlled pH of either 7.0 or 7.2, resulted in productivity improvement in 5 L and 200 L bioreactors, yielding 737 and 830 mg/ml of YYB-101, respectively. The YYB-101 mAb highly purified by affinity chromatography using a Protein A column and two-step ion exchange chromatography effectively neutralized HGF in a cell-based assay and showed potent tumor suppression activity in a mouse xenograft model established with human glioblastoma cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.1
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• pp.37-47
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• 2011

This study was aimed to investigate the memory enhancing effect of Jeongjihwan against scopolamine-induced amnesia in C57BL/6 mice. To determine the effect of Jeongjihwan on the memory and cognitive function, we have injected scopolamine (1 mg/kg, i.p.) into C57BL/6 mice 30 min before beginning of behavior tests. We have conducted Y-maze, Morris water-maze, passive avoidance and fear conditioning tests to compare learning and memory functions. Scopolamine-induced behavior changes of memory impairment were significantly restored by oral administration of Jeongjihwan (100 or 200 mg/kg/day). To elucidate the molecular mechanism underlying the memory enhancing effect of Jeongjihwan, we have examined the antioxidant defense system and neurotrophic factors. Jeongjihwan treatment attenuated intracellular accumulation of reactive oxygen species and up-regulated mRNA and protein expression of antioxidant enzymes as assessed by RT-PCR and western blot analysis, respectively. Jeongjihwan also increased protein levels of brain-derived neurotrophic factor (BDNF) compared with those in the scopolamine-treated group. Furthermore, as an upstream regulator, the activation of cAMP response element-binding protein (CREB) via phosphorylation was assessed by Western blot analysis. Jeongjihwan elevated the phosphorylation of CREB (p-CREB), which seemed to be mediated partly by extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase B/Akt. These findings suggest that Jeongjihwan may have preventive and therapeutic potential in the management of amnesia.

• CELLMED
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• v.7 no.2
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• pp.8.1-8.7
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• 2017

Benign prostatic hyperplasia (BPH) is one of the major diseases of the urinary system in older men. WSY-0702 is the extracted from the traditional medicinal plant; Seoritae, and it has effects of anti-obesity, chronic cervical pain, and anti-oxidant. The present study aimed to investigate the therapeutic potential of WSY-0702 in the prevention and treatment of BPH. Several parameters including inflammatory mediators, hormones, and oxidative stress (OS) have been considered to play a role in the development of BPH. Prostate tissue damage and OS may lead to compensatory cellular proliferation with resulting hyperplastic growth. An in vitro study showed that proliferation inhibited the human prostate epithelial cell line RWPE-1 in a dose-dependent manner. In cell line, the cell cycle at the G2/M and G0/G1 phase and downregulated the expression of CyclineB1 (CCNB1) and CyclineD1 (CCND1). In addition, we measured the $H_2O_2$-induced OS damage using RWPE-1 cells. We examined the relative expression of protein involved in the regulation of prostate apoptosis: transforming growth factor (TGF)-${\beta}$, a negative growth factor able to induced prostate apoptosis under physiological conditions. These results suggest that WSY-0702 that can inhibit the growth of prostate epithelial cell by a mechanism that may involve arresting the cell cycle and downregulating CCNB1 and CCND1 expression. In addition, WSY-0702 exposure resulted in significant protective effects in $H_2O_2$-stressed PWPE-1 cells by reduction in TGF-${\beta}$ levels.

• Journal of dental hygiene science
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• v.18 no.3
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• pp.188-193
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• 2018

The aim of the current study was to demonstrate the potential therapeutic efficacy of resveratrol in oral cancer patients. Lysophosphatidic acid (LPA) intensifies cancer cell invasion and metastasis, whereas resveratrol, a natural polyphenolic compound, possesses antitumor activity, suppressing cell proliferation and progression in various cancer cell lines (ovarian, gastric, oral, pancreatic, colon, and prostate cancer cells). In addition, resveratrol has been identified as an inhibitor of LPA-induced proteolytic enzyme expression and ovarian cancer invasion. Furthermore, resveratrol was shown to inhibit oral cancer cell invasion by downregulating hypoxia-inducible factor $1{\alpha}$ and vascular endothelial growth factor expression. Recently, we demonstrated that LPA is important for the expression of transcription factors TWIST and SLUG during epithelial-mesenchymal transition (EMT) in oral squamous carcinoma cells. In this study, we treated serum-starved cultures of oral squamous carcinoma cell line YD-10B with resveratrol for 24 hours prior to stimulation with LPA. To identify an optimal resveratrol concentration that does not induce apoptosis in oral squamous carcinoma cells, we determined the toxicity of resveratrol in YD-10B cells by assessing their viability using the MTT assay. Another assay was performed using Matrigel-coated cell culture inserts to detect oral cancer cell invasion activity. Immunoblotting was applied for analyzing protein expression of SLUG, TWIST1, E-cadherin, and GAPDH. We demonstrated that resveratrol efficiently inhibited LPA-induced oral cancer cell EMT and invasion by downregulating SLUG and TWIST1 expression. Therefore, resveratrol may potentially reduce oral squamous carcinoma cell invasion and metastasis in oral cancer patients, improving their survival outcomes. In summary, we identified new targets for the development of therapies against oral cancer progression and characterized the therapeutic potential of resveratrol for the treatment of oral cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5303-5307
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• 2016

Objective: Brain tumors cause great mortality and morbidity worldwide, and success rates with surgical treatment remain very low. Several recent studies have focused on introduction of novel effective medical therapeutic approaches. Genistein is a member of the isoflavonoid family which has proved to exert anticancer effects. Here we assessed the effects of genistein on the expression of MMP-2 and VEGF in low and high grade gliomas in vitro. Materials and Methods: High and low grade glioma tumor tissue samples were obtained from a total of 16 patients, washed with PBS, cut into small pieces, digested with collagenase type I and cultured in DMEM containing 10% FBS. When cells reached passage 3, they were exposed to genistein and MMP-2 and VEGF gene transcripts were determined by quantitative real time PCR (qRT-PCR). Results: Expression of MMP-2 demonstrated 580-fold reduction in expression in low grade glioma cells post treatment with genistein compared to untreated cells (P value= 0.05). In cells derived from high grade lesions, expression of MMP-2 was 2-fold lower than in controls (P value> 0.05). Genistein caused a 4.7-fold reduction in VEGF transcript in high grade glioma cells (P value> 0.05) but no effects were evident in low grade glioma cells. Conclusion. Based on the data of the present study, low grade glioma cells appear much more sensitive to genistein and this isoflavone might offer an appropriate therapeutic intervention in these patients. Further investigation of this possibility is clearly warranted.

• Korean Journal of Pharmacognosy
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• v.50 no.3
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• pp.191-197
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• 2019

Sepsis, an infectious disease, is a life-threatening condition that arises when the response to infection causes injury to tissues and organs. The purpose of this study was to demonstrate whether ABHC-1 and ABHC-2, two functional extracts from herbal complex, have an anti-bacterial effect against Escherchia coli in vivo, in vitro experimental model. ABHC-1 and ABHC-2 showed the antibacterial activity against the bacteria by paper disc method. The minimum inhibitory concentration (MIC) was measured using alamar blue reagent. The MIC was shown at $60{\mu}g/ml$ from ABHC-1 and $500{\mu}g/ml$ from ABHC-2 against E. coli. We next examined the effect of ABHCs on the production of inflammatory cytokine, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), which is related to the induction of inflammation, in RAW 264.7 cell. ABHC-1 and ABHC-2 increased $TNF-{\alpha}$ production of RAW 264.7 cell in a dose-dependent manner while two extract decreased $TNF-{\alpha}$ production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell in a dose-dependent manner. At a dose of $1{\times}10^8$ E. coli. i.p., non-treated mice were succumbed, while most of mice treated with ABHC-1 were survived. Therefore, our results suggest that ABHC-1 has anti-bacterial activity and can be a novel therapeutic agent against infectious diseases.