• Journal of Applied Biological Chemistry
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• v.66
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• pp.39-45
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• 2023

Biorenovation is a biotransformation method that converts the structure of chemical compounds and natural product through biocatalytic metabolism of microorganism and could enhance biological effectiveness and mitigate cytotoxicity compared to its substrates. Althaea rosea L. has been used as oriental medicine and is known for physiological efficacies such as antiurolithiatic, anti-inflammatory, and anti-cancer activities. A. rosea L. callus, the plant tissue grown to protect its wound, has been reported to have antioxidant and whitening effects. However, mechanisms of its other activity such as inflammation have not yet been investigated. In this study, we extracted A. rosea L. callus (AR) and produced biorenovated AR (ARBR), and then analyzed anti-inflammatory effect in Lipopolysaccharide-induced RAW 264.7 macrophage at 50, 100, 200 ㎍/mL of ARBR. As a result of inhibition test of nitric oxide production, it was found that ARBR was superior to AR without apparent toxicity. Furthermore, ARBR significantly inhibited production of prostaglandin E₂, inducible nitric oxide synthase, cyclooxygenase-2 and pro-inflammatory cytokines including Tumor necrosis factor-α, Interleukin-6, Interleukin-1β in a concentration-dependent manner. In conclusion, we suggest that ARBR could regulate the excessive inflammatory response to an appropriate level and be a promising material for functional cosmetics and pharmaceuticals.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.46-52
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• 2023

The most abundant flavanone of grapefruits, naringenin (NN), is well known for its hepatoprotective, anti-lipid peroxidation and anti-carcinogenic effects. We generated three derivatives from NN using this technique in previous studies. Among them, it was confirmed that naringenin-7-O-phosphate (N7P), whose biological and physicochemical properties were not reported, showed a water solubility 45 times higher than that of NN. Therefore, in this study, the anti-inflammatory activity was evaluated in RAW 264.7 cells to investigate the potential physiological activity of N7P. As a result, N7P showed nitric oxide (NO) inhibitory activity at concentrations that did not show toxicity. In addition, prostaglandin E₂ (PGE₂) showed significant inhibitory activity from the lowest concentration of 12.5 μM and showed increased inhibitory activity compared to NN. In addition, as a result of western blot, N7P showed increased cyclooxygenase-2 (COX-2) inhibitory activity than NN, and effectively inhibited NO and PGE₂ by significantly inhibiting their expression pathways. N7P also inhibited inflammatory cytokines, including tumor necrosis factor-α, interleukin-6. Based on these results, we propose that N7P can be used as a potent antiinflammatory agent.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.627-637
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• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

• Journal of Korean Tunnelling and Underground Space Association
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• v.26 no.3
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• pp.209-222
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• 2024

The Earth Pressure Balance (EPB) shield Tunnel Boring Machine (TBM) is widely used for underground tunnel construction for its advantages, such as eliminating the need for additional facilities compared to the slurry shield TBM, which requires Slurry Treatment Plant (STP). During EPB shield TBM excavation, a soil conditioning technique is employed to enhance the physical properties of the excavated soil by injecting additives, thus broadening the range of applicable ground conditions to EPB shield TBMs. This study explored the use of xanthan gum, a type of biopolymer, as an alternative to the commonly used polymer additive. Biopolymers, derived from biological sources, are fully biodegradable. In contrast to traditional polymers such as polyacrylic acid, which contain environmentally harmful components, xanthan gum is gaining attention as an eco-friendly material due to its minimal toxicity and environmental impact. Test conditions with similar workability were established through slump tests, and the rheological characteristics were assessed using a laboratory pressurized vane shear test apparatus. The experiments demonstrated that, despite exhibiting similar workability, the peak strength in the flow curve decreased with increasing the content of xanthan gum. Consequently, a correlation between the xanthan gum content and peak strength was established. Replacing the traditional polymers with xanthan gum could enable stable EPB shield TBM operation by reducing equipment load, in addition to offering environmental benefits.

• International Journal of Stem Cells
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• v.15 no.3
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• pp.258-269
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• 2022

Background and Objectives: Currently, safety pharmacological tests for the central nervous system depend on animal behavioral analysis. However, due to the subjectivity of behavioral analysis and differences between species, there is a limit to appropriate nervous system toxicity assessment, therefore a new neurotoxicity assessment that can simulate the human central nervous system is required. Methods and Results: In our study, we developed an in vitro neurotoxicity assessment focusing on neuronal function. To minimize the differences between species and fast screening, hiPSC-derived neurons and a microelectrode array (MEA) that could simultaneously measure the action potentials of the neuronal networks were used. After analyzing the molecular and electrophysiological characters of our neuronal network, we conducted a neurotoxicity assessment on neurotransmitters, neurotoxicants, illicit drugs, and new psychoactive substances (NPS). We found that most substances used in our experiments responded more sensitively to our MEA-based neurotoxicity assessment than to the conventional neurotoxicity assessment. Also, this is the first paper that evaluates various illicit drugs and NPS using MEA-based neurotoxicity assessment using hiPSC-derived neurons. Conclusions: Our study expanded the scope of application of neurotoxicity assessment using hiPSC-derived neurons to NPS, and accumulated evaluation data of various toxic substances for hiPSC-derived neurons.

• Journal of the Korean Applied Science and Technology
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• v.41 no.3
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• pp.543-554
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• 2024

In this study, the anti-inflammatory, anti-bacterial and anti-oxidative activities of subcritical water extract from Chamaecyparis obtusa leaves was compared with hot water extract. The yield of subcritical water extract (165℃ and 180℃, 80 bar) was 39.4~48.5%, higher than 31.5% of hot water extract. In the anti-inflammatory tests using lipopolysaccaride (LPS)-induced RAW264.7 macrophages, the subcritical water extract concentration-dependently inhibited production of nitric oxide (NO) without causing cell toxicity. Upon the anti-bacterial studies using Cutibacterium acnes and Staphylococcus epidermidis, subcritical water extract showed the stronger activity than hot water extract. In addition, DPPH and ABTS cation radical scavenging activity experiments showed that the radical scavenging activity of subcritical water extract was similar to that of hot water extract. Moreover, in the study of cell protection effect using HaCaT keratinocytes damaged by hydrogen peroxide (H₂O₂), the subcritical water extract (165℃, 80 bar) indicated protective effect against oxidative stress. These results suggested that the subcritical water extract of C. obtusa leaves as natural ingredients could be used as anti-inflammatory, anti-bacterial and anti-oxidative ingredients in cosmetic formulations.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.50 no.3
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• pp.227-237
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• 2024

In this study, we investigated anti-oxidative, anti-inflammatory and anti-bacterial constituents from the extract of Prunus mume (P. mume) branches. Five phytochemicals were isolated from the ethyl acetate (EtOAc) fraction of P. mume branches; noreugenin (1), naringenin (2), prunin (3), procyanidin A2 (4) and epiafzelechin-(2β→O→7, 4β→8)-epicatechin (5). The chemical structures of isolated compounds were elucidated based on the spectroscopic data including NMR spectra as well as comparison of the data to the literature values. Upon the anti-oxidative studies by DPPH and ABTS⁺ radicals, potent radical scavenging activities were observed in the extract, EtOAc, n-butanol (BuOH) fractions and isolated compounds 4, 5. In the anti-inflammatory tests using RAW 264.7 macrophages, the n-hexane (Hex), EtOAc fractions and compounds 1-5 inhibited production of nitric oxide (NO) without causing cell toxicity. Also, the extract, n-Hex, EtOAc and n-BuOH fractions showed anti-bacterial activities against Staphylococcus epidermidis and Cutibacterium acnes. Based on these results, it was suggested that the extract, solvent fractions and phytochemicals from P. mume branches could be applicable as natural source for cosmetic ingredients.

• Radiation Oncology Journal
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• v.15 no.1
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• pp.27-36
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• 1997

Purpose : This study was tried to evaluate the Potential benefits of concurrent chemoradiation therapy (low dose daily cisplatin combined with split course radiation therapy) compared with conventional radiation therapy alone in stage III non-small cell lung cancer. The end points of analyses were response rate. overall survival, survival without locoregional failure, survival without distant metastasis, prognostic factors affecting survival and treatment related toxicities. Materials and Methods : Between April 1992 and March 1994, 32 patients who had stage III non-small cell lung cancer were treated with concurrent chemoradiation therapy. Radiation therapy for 2 weeks (300 cGy given 10 times up to 3000 cGy) followed by a 3 weeks rest period and then radiation therapy for 2 more weeks (250 cGy given 10 times up to 2500 cGy) was combined with $6mg/m^2$ of cisplatin. Follow-up period ranged from 13 months to 48 months with median of 24 months. Historical control group consisted of 32 patients who had stage III non-small cell lung cancer were received conventionally fractionated (daily 170-200 cGy) radiation therapy alone. Total radiation dose ranged from 5580 cGy to 7000 cGy with median of 5940 cGy. Follow-up Period ranged from 36 months to 105 months with median of 62 months. Result : Complete reponse rate was higher in chemoradiation therapy (CRT) group than radiation therapy (RT) group (18.8% vs. 6.3%, CRT group showed lower in-field failure rate compared with RT group(25% vs. 47%. The overall survival rate had no significant differences in between CRT group and RT group (17.5% vs. 9.4% at 2 years). The survival without locoregional failure (16.5% vs. 5.3% at 2 years) and survival without distant metastasis (17% vs. 4.6% at 2 years) also had no significant differences. In subgroup analyses for Patients with good performance status (Karnofsky performance scale 80), CRT group showed significantly higher overall survival rate compared with RT group (62.5% vs. 15.6% at 2 years). The prognostic factors affecting survival rate were performance status and pathologic subtype (squamous cell cancer vs. nonsquamous cell cancer) in CRT group. In RT alone group, performance status and stage (IIIa vs IIIb) were identified as a Prognostic factors. RTOG/EORTC grade 2-3 nausea and vomiting(22% vs 6% and bone marrow toxicities (25% vs. 15.6% were significantly higher in CRT group compared with RT alone group. The incidence of RTOG/EORTC grade 3-4 pulmonary toxicity had no significant differences in between CRT group and RT group (16% vs. 6%. The incidence of WHO grade 3-4 pulmonary fibrosis also had no significant differences in both group (38% vs. 25%. In analyses for relationship of field size and Pulmonary toxicity, the Patients who treated with field size beyond 200cm2 had significantly higher rates of pulmonary toxicities. Conclusion : The CRT group showed significantly higher local control rate than RT group. There were no significant differences of survival rate in between two groups. The subgroup of patients who had good performance status showed higher overall survival rate in CRT group than RT group. In spite of higher incidence of acute toxicities with concurrent chemoradiation therapy, the survival gain in subgroup of patients with good performance status were encouraging. CRT group showed higher rate of early death within 1 year, higher 2 year survival rate compared with RT group Therefore, to evaluate the accurate effect on survival of concurrent chemoradiation therapy, systematic follow-up for long term survivors are needed.

• Korean Journal of Animal Reproduction
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• v.24 no.3
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• pp.241-248
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• 2000

In this study, we examined the number and motility of sperms, and also observed the changes in testes weight, and histological changes of several organs after 5 days of a continuous administration of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) of per oral administration of a herb drug extracts, which were administerated altermate days, to elucidate the effects of the a herb drug extracts on reproductive toxicity of dioxin. 1. The sperm numbers of dioxin-administered groups were 90.7$\pm$3.6~l18.5$\pm$3.6$\times$10/suup 6/$m\ell$ and 67.3$\pm$4.1~88.2$\pm$3.3$\times$10$^{6}$ $m\ell$ for 10~20 $\mu\textrm{g}$/kg and 30~40 $\mu\textrm{g}$/kg dosages of dioxin-administerated groups, respectively. Each dioxin-administered group showed prominently lower value than that of control group's which was 119.3$\pm$3.4~120.2$\pm$4.7 $\times$ 10$^{6.}$$m\ell$. 2. The sperm motility of each dioxin-administered group's also showed lower value than that of control group's which was 93.6$\pm$3.8~94.9$\pm$3.4%. The sperm motility of each dioxin-administerated group were 77.0$\pm$4.7~89.5$\pm$3.6% and 66.5$\pm$3.3 ~79.9$\pm$3.8% for 10~20 $\mu\textrm{g}$/kg and 30~40 $\mu\textrm{g}$/kg dosages of dioxin-administerated groups, respectively. 3. The sperm numbers of each group, which was administered a herb drug extracts, were 77.4$\pm$3.2~90.9$\pm$3.4$\times$10$^{6}$ $m\ell$, 78.0$\pm$3.3~105.0$\pm$4.2$\times$10$^{6}$ $m\ell$, 76.2$\pm$2.8~84.4$\pm$3.5$\times$10$^{6}$ $m\ell$ and 75.4$\pm$3.3~80.2$\pm$3.3$\times$10$^{6}$ $m\ell$ for extracts of green leaf, red ginseng, Kugija and Oume-administered groups respectively. And the sperm motility of each group were 63.4$\pm$3.8~77.0$\pm$4.0%, 65.5$\pm$4.1~87.4$\pm$3.8%, 64.3$\pm$4.2~69.8$\pm$4.2%, 66.3$\pm$3.9~66.0$\pm$4.0% for extracts of green leaf, red ginseng, Kugija and Oume extracts-administered groups, respectively. 4. The number and motility of sperm of control group were 119.3$\pm$3.4~120.2$\pm$4.7$\times$10$^{6}$ $m\ell$ and 93.0$\pm$3.5~96.1$\pm$3.5%, respectively. Red ginseng extracts- administered group seemed to be recovered than my other groups, and the green leaf extracts-administered group was shown to be the next. The Kugija and Oume extracts-administered groups didn't show to be recovered much. 5. Most a herb drug extracts-administered group except the red ginseng-administered group displayed prominently lower values of testes weights than that of control group's which was 0.15$\pm$0.01~0.16$\pm$0.01g. The red ginseng extracts-administered group seemed to be recovered conspicuously. 6. After 5 days of a continuous administration of 30 $\mu\textrm{g}$/kg dosage of dioxin followed by 3 weeks of per oral administration of green leaf, red ginseng, Kugija, or Oume extracts, histological findings showed that the liver, spleen, and testis of most a herb drug extracts-administered groups were damaged severely. By the way, the testes of red ginseng extracts-administered group seemed to recover compared to the other group's.ompared to the other group's.

• Journal of Applied Biological Chemistry
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• v.57 no.3
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• pp.219-225
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• 2014

Azadirachta indica extract (AIE) has been regarded as a promising source of environment-friendly organic materials owing to their low mammalian toxicity. However, quite a bit of research has been reported that AIE may cause clastogens in human lymphocytes. Therefore, this study was conducted to evaluate the antimutagenic and genotoxicity of two samples of AIE. Antimutagenic test was experimented by using bacterial reverse mutation test. In the bacterial reverse mutation test, five strains Salmonella Typhimurim of two samples of AIE in order to evaluate its mutagenic potential. Bacterial reverse mutation test was also performed on positive control and negative control groups in the presence of the metabolic activation system (S-9 mix) and metabolic non-activation system. In the chromosome aberration test, Chinese hamster lung cells were exposed to AIE for 6 or 24 h with BPS, or for 6 h with S-9 mix. Negative and positive control groups were experimented for chromosome aberration test. As a result, the number of mutated colonies induced by 4-NQO were reduced by AIE treatment in all strains, indicating that AIE may have antimutagenic effects. Bacterial reverse mutation and chromosomal aberration were not shown at all concentration of AIE, regardless of activation of the metabolic system. we concluded that two AIE samples used in this study have no genotoxic effects to human, according to the genotoxicity battery system suggested by ICH (International Conference on Harmonization).