• Title/Summary/Keyword: $IL-1{\beta}$, IL-4, IL-10)

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Relationship between Radiosensitivity and Repair Capacity in Human Epithelial Cancer Cell Lines (인체 상피암 세포주에서 방사선감수성과 손상회복의 상관관계에 관한 연구)

  • Koh, Kyoung-Hwan;Ha, Sung-Whan;Park, Charn-Il
    • Radiation Oncology Journal
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    • v.11 no.1
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    • pp.17-27
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    • 1993
  • To investigate the relationship between radiosensitivity and postirradiation recovery in human cancer cells, a study was performed using human cancer cell lines-A549, CaSki, SNU-C5 and PCI-13. For the study of radiosensitivity, single doses of 2, 4, 6, 8, 10, 12, and 14 Gy were given and for postirradiation recovery, two fractions of 4 Gy were separated with a time interval of 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, or 6 hours. Surviving fraction was estimated using colony forming ability. Surviving fractions at 2 Gy (SF2) were 0.496 (0.570-0.412) for A549, 0.496 (0.660-0.332) for CaSki, 0.386 (0.576-0.216) for SNU-C5, and 0.185 (0.247-0.123) for PCI-13. By statistical analysis the SF2 of PCI-13 was lower significantly than those of others (p<0.05). This difference was also observed at 4, 6 and 8 Gy dose levels. At 6 and 8 Gy the surviving fractions of SNU-C5 were also lower significantly than A549 and CaSki (p<0.05). By the analysis with linear quadratic model, the values of ${\alpha}$ for A549, CaSki, SNU-C5 and PCI-13 were 0.3016, 0.3212, 0.4327 and 0.8423, respectively, and those of ${\beta}$ were 0.02429, 0.02009, 0.03349 and 0.00059, respectively. So, the value of ${\alpha}$ showed increasing tendency with decreasing SF2. By the multitarget single hit model the values of Do for A549, CaSki, SUN-C5 and PCI-13 were 1.97, 1.97, 1.46 and 0.81, respectively, and those of n were 1.53, 1.50, 1.56 and 2.28, respectively. So, the value of Do decreased with decreasing SF2. Post-irradiation recovery reached plateau at around 2 hours. Recovery ratio at plateau phase ranged from 1.2 to 4.2; the value were 1.2 for PCI-13, 3.2 for CaSki, 3.3 for SNU-C5, and 4.2 for A549. Recovery rate well correlated with SF2, and increased with increasing Do and decreasing ${\alpha}$. According to above results, the intrinsic radiosensitivity was quite different among the tested cell lines; PCI-13 was the most sensitive and A549 and CaSki was similar. This difference of radiosensitivity is thought to be partly due to the difference in amount of postirradiation recovery. By linear quadratic model the difference of ${\alpha}$ values was very high, and by multitarget single hit model the difference of Do value was significantly high among four cell lines.

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In Vitro and In Vivo Effects of Piceatannol and Resveratrol on Glucose Control and TLR4-NF-κB Pathway (피세아테놀과 레스베라트롤의 혈당조절 및 TLR4-NF-κB 경로 조절 작용)

  • Lee, Hee Jae;Lee, Hae-Jeung;Yang, Soo Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.2
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    • pp.267-272
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    • 2017
  • Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV), which is a polyphenol known to extend lifespan by stimulating sirtuins. The aim of this study was to investigate the effects of PIC and RSV on the toll-like receptor 4 (TLR4)-nuclear factor kappa B ($NF-{\kappa}B$) pathway in mouse hepatocytes and an obese/diabetic KK/HlJ mouse model. AML12 mouse hepatocytes in the absence or presence of palmitic acids (PA) were treated with PIC ($50{\mu}M$) or RSV ($50{\mu}M$). Male KK/HlJ mice at 20 weeks of age were divided into three subgroups as follows: 1) obese and diabetic control (KK), 2) KK_PIC, and 3) KK_RSV. PIC and RSV were administered orally at a dose of 10 mg/kg/d for 4 weeks. Four weeks of PIC and RSV treatment did not affect body weight or food intake in KK mice. Serum fasting blood glucose was significantly reduced in KK_PIC, and 2 h oral glucose tolerance test area under the curve was significantly reduced by PIC and RSV treatment in KK mice. PIC tended to improve homeostasis model assessment of the insulin resistance index (HOMA-IR) and HOMA beta-cells in diabetic KK mice. TLR4 and $NF-{\kappa}B$ were down-regulated by PIC and RSV treatments in hepatocytes in the absence or presence of PA. Insulin receptor, AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma, nucleotide oligomerization domain-like receptor family pyrin domain-containing 3, interleukin-1, and $NF-{\kappa}B$ were altered in PIC-treated livers. Collectively, PIC and RSV inhibited the $TLR4-NF-{\kappa}B$ pathway, and PIC seems to be more effective than RSV in the regulation of analyzed targets, which are involved in insulin signaling and inflammation in vivo.

Changes of Hepatic Cyclohexane Metabolizing Enzyme Activities and Its Metabolites in Serum and Urine after Cyclohexane Treatment

  • Kim Ji-Yeon;Jeon Tae-Won;Lee SangHee;Chung Chinkap;Joh Hyun-Sung;Lee Sang-Il;Yoon Chong-Guk
    • Biomedical Science Letters
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    • v.11 no.4
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    • pp.509-515
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    • 2005
  • This study was conducted to determine the kinetics of cyclohexane metabolites (the biomarker on cyclohexane exposure), the changes of hepatic cyclohexane metabolizing enzyme activities and the metabolites of cyclohexane in urine or serum. The rats were sacrificed at 2, 4, 8, 12 and 24 hr after administration of one dose of cyclohexane (1.56 g/kg body weight, i.p.). The metabolites of cyclohexane in urine were identified as cyclohexanol, cyclohexanone, trans-l,2-cyclohexanediol and 1,4-cyclohexanediol with cyclohexane metabolite being 124.00, 0.78, 23.28 and 2.75 (g/g of creatinine, $1\times10^{-3}$). Most of the cyclohexanol and trans-l,2-cyclohexanediol were determined to be in the form of $\beta-glucuronide$ conjugates, whereas cyclohexanone and 1 ,4-cyclohexanediol were found as free forms. In toxicokinetics of serum cyclohexane metabolites, cyclohexanol showed a rapid increase, reaching the plateau at 4 hr, after this time rapidly decreased throughout 24 hr. Changes of cyclohexanone also showed the similar pattern with cyclohexanol except somewhat lower concentration. Trans-l,2-cyclohexanediol, however, showed a gradual increase until 12 hr with the continued same levels throughout 24 hr. On the other hand, 1,4-cyclohexanediol was detected as trace levels at 4 and 12 hr, respectively. The administration of cyclohexane led to a significant increase of hepatic aniline hydroxylase activity from 2 to 8 hr. The activity of hepatic alcohol dehydrogenase showed a significant increase at 4 hr and then were recovered to the level of the control at 24 hr. On the other hand, there were no differences in liver weightlbody weight between the control and cyclohexane-treated animals. However, there were the changes of aniline hydroxylase and alcohol dehydrogenase activities on time-dependent pattern after cyclohexane treatment, which influence on the degree of cyclohexane metabolites both in blood and urine. These results suggest that differential determination of cyclohexane metabolites in urine and serum may be able to be as a biomarker of cyclohexane-exposure in the body. But in this fields further study is needed.

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Determination of Terazocin in Human Plasma by Liquid Chromatography and Bioequivalence Study of Teratonin® Tablets (액체크로마토그래프법에 의한 사람 혈장 중 테라조신의 정량 및 테라토닌® 정의 생물학적 동등성)

  • Cho, Eun-Sook;Kang, Sung-Ha;Chun, In-Koo
    • Journal of Pharmaceutical Investigation
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    • v.32 no.2
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    • pp.119-125
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    • 2002
  • A rapid, selective and reproducible high-performance liquid chromatographic method has been developed for the determination of terazocin in human plasma. Terazocin plus the internal standard, prazocin hydrochloride, were extracted from alkalified plasma with tert-butylmethyl ether, back-extracted into 0.05% phosphoric acid. Fifty ${\mu}l-portions$ of extract were injected onto a octadecylsilane column and eluted with a mixture of acetonitrile, water and triethylamine (30 : 70 : 0.1 v/v, adjusted to pH 5.0 with dilute phosphoric acid) at a flow rate of 1.0 ml/min. The fluorescence intensity of column eluents was monitored at excitation wavelength of 250 nm and emission wavelength of 370 nm. No interference peaks were observed. The practical limit of quantitation was 5 ng/ml for terazocin. The average intraday and interday coefficients of variation were 4.15 and 3.54%, respectively. Also intraday and interday precisions over the range $5{\sim}60\;ng/ml$ were $0.49{\sim}2.92\;and\;0.38{\sim}5.12%$, respectively. The bioequivalence of two terazosin tablets, the $Hytrine^{\circledR}$ (Il Yang Pharmaceutical Co., Ltd.) and the $Teratonin^{\circledR}$ (Sam-A Pharmaceutical Co., Ltd.), was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Sixteen healthy male volunteers $(24.6{\pm}2.0\;years\;old)$ were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 2 mg of terazosin was orally administered, blood was taken at predetermined time intervals and the concentration of terazosin in plasma was determined with a HPLC method using spectrofluorometric detector. AUC was calculated by the linear trapezoidal method. $C_{max}\;and\;T_{max}$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between the two preparations were 0.21 %, 5.53% and 8.82%, respectively. The powers $(1-{\beta})\;for\;AUC_t,\;C_{max}\;and\;T_{max}$ were >99%, 97.49%, and 33.26%, respectively. Minimum detectable differences $({\Delta},\;%)\;at\;{\alpha}=0.1\;and\;1-{\beta}=0.8$ and the 90% confidence intervals were all less than ${\pm}20%$ except for $T_{max}.\;AUC_t\;and\;C_{max}$ met the criteria of KDFA for bioequivalence, indicating that $Teratonin^{circledR}$ tablets are bioequivalent to $Hytrine^{circledR}$ tablets.

Antioxidative Effects of Peanut Sprout Extracts (땅콩나물 추출물의 항산화 효과)

  • Kang, Hye-In;Kim, Jae-Yong;Kwon, Soon-Jae;Park, Kyung-Wuk;Kang, Jum-Soon;Seo, Kwon-Il
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.7
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    • pp.941-946
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    • 2010
  • For the long-term goal of using peanut sprouts as a functional food material, the total polyphenol content and the antioxidant activity of methanol extracts were examined with use of 9 day-old peanut sprouts and peanuts collected in Chungbuk, Gyeongbuk and Jeonbuk provinces of Korea, China and Vietnam. The polyphenol levels in the sprout extracts were higher than those of the peanut extracts. The phenolic content of the Gyeongbuk peanut sprout extract (20.4 mg/g) was the highest of the tested samples. After 9 days of germination the peanut sprout extracts had higher activities than those of the peanut extracts. In particular, the activity of Gyeongbuk peanut sprout extract was the highest (37.67% at a concentration of $200\;{\mu}L/mL$), and its reducing power demonstrated a similar trend. The DPPH radical scavenging activities were measured for methanol extracts of cotyledon, root and stem of Gyeongbuk peanut sprouts; the highest (90.96% at a concentration of $200\;{\mu}L/mL$) was the activity of cotyledon. ABTS radical scavenging and $\beta$-carotene bleaching activities also were higher in the cotyledon extract than in those of the root or the stem. The resveratrol content was higher in the Gyeongbuk peanut sprout extract than in the Gyeongbuk peanut extract ($15.05\;{\mu}g/g $and $1.42\;{\mu}g/g$, respectively). These results suggest that peanut sprouts potentially could be used as a functional food material exhibiting antioxidant effects.

Esculetin Induces Apoptosis through Caspase-3 Activation in Human Leukemia U937 Cells (Esculetin의 caspase-3 활성을 통한 U937 인체 혈구암세포의 세포사멸 유도)

  • Park, Cheol;Hyun, Sook-Kyung;Shin, Woo-Jin;Chung, Kyung-Tae;Choi, Byung-Tae;Kwon, Hyun-Ju;Hwang, Hye-Jin;Kim, Byung-Woo;Park, Dong-Il;Lee, Won-Ho;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.19 no.2
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    • pp.249-255
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    • 2009
  • Esculetin, a coumarin compound, has been known to inhibit proliferation and induce apoptosis in several types of human cancer cells. However, the molecular mechanisms involved in esculetin-induced apoptosis are still uncharacterized in human leukemia cells. In this study, we have investigated whether esculetin exerts anti-proliferative and apoptotic effects on human leukemia U937 cells. It was found that esculetin could inhibit cell viability in a time-dependent manner, which was associated with the induction of apoptotic cell death such as increased populations of apoptotic- sub G1 phase. Apoptosis of U937 cells by esculetin was associated with an inhibition of Bcl-2/Bax binding activity, formation of tBid, down-regulation of X-linked inhibitor of apoptotic protein (XIAP) expression, and up-regulation of death receptor 4 (DR4) and FasL expression. Esculetin treatment also induced the degradation of ${\beta}$-catenin and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Furthermore, a caspase-3 specific inhibitor, z-DEVD-fmk, significantly inhibited sub-G1 phase DNA content, morphological changes and degradation of ${\beta}$-catenin and DEE45/ICAD. These results indicated that a key regulator in esculetin-induced apoptosis was caspase-3 in human leukemia U937 cells.

Indigo Naturalis in Inflammatory Bowel Disease: mechanisms of action and insights from clinical trials

  • Hyeonjin Kim;Soohyun Jeong;Sung Wook Kim;Hyung-Jin Kim;Dae Yong Kim;Tae Han Yook;Gabsik Yang
    • Journal of Pharmacopuncture
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    • v.27 no.2
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    • pp.59-69
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    • 2024
  • This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1β) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-β) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

β-Glucan Content and Antioxidant Activity of Mixed Extract from Sarcodon aspratus and Rice Bran (능이버섯과 미강 혼합 추출물의 β-Glucan 함량 및 항산화 활성)

  • Sim, Wan-Sup;Choi, Sun-Il;Jung, Tae-Dong;Cho, Bong-Yeon;Choi, Seung-Hyun;Han, Xionggao;Lee, Jin-Ha;Seo, Yu-Ri;Kim, Hye-Been;Lim, Ki-Taek;Lee, Ok-Hwan
    • Journal of Food Hygiene and Safety
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    • v.33 no.3
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    • pp.200-206
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    • 2018
  • This study was to investigate the optimal condition of mixture ratio for development of functional food ingredient from Sarcodon aspratus and rice bran. First, $^{\circ}Brix$ was measured along with extraction time. Five kinds of mixtures of Sarcodon aspratus and rice bran (10:0, 7:3, 5:5, 3:7, 0:10) were extracted in $95^{\circ}C$ water over a one-hour period and the extraction yield was evaluated. We further evaluated ${\beta}-glucan$ content, DPPH radical scavenging activity, ferric ion reducing antioxidant power (FRAP), total phenolic content and total flavonoids content. As a result, both Sarcodon aspratus and rice bran showed a constant $^{\circ}Brix$ after 45 minutes of extraction time. The content of ${\beta}-glucan$ was highest in the Sarcodon aspratus and rice bran mixture with a ratio of 3:7. As the ratio of rice bran increased in all mixtures, the antioxidant capacity also increased. In conclusion, to create a functional food ingredient the optimal mixing ratio of Sarcodon aspratus to rice bran is 3:7.

Assessment of Renal Function in Silicobis with Urinary N-acetyl-$\beta$-D-glucosaminidase Activity (규폐증환자의 신기능 평가를 위한 요중 N-acetyl-$\beta$-D-glucosaminidase활성치 측정의 의의)

  • Lee, Hoo-Rak;Kim, Don-Kyoun;Lee, Su-Il;Cho, Byung-Mann;Kim, Wha-Jo
    • Journal of Preventive Medicine and Public Health
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    • v.26 no.1 s.41
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    • pp.49-64
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    • 1993
  • To provide the basic data for assessment of renal dysfunction related to silicosis, urinary N-acetyl-$\beta$-D-giucobarninidase(NAG) activity known as a sensitive markers for early renal damage were measured in 58 silicosis patients, and control subjects of 40 pulmonary tuberculosis Patients and 51 official workers. The results were summarized as fellows. 1. The values of blood urea nitrogen and serum creatinine in all subjects were within reference limits. But the mean value of urinary NAG activity($7.25{\pm}7.31U/g\;creatinine$) was beyond reference value and more sensitive test than others. 2. The mean value of urinary NAG activity in silicosis group was $11.98{\pm}9.05U/g\;creatinine$ and significantly higher than in tuberculosis and healthy group(p<0.01), but the mean values of NAG activity in tuberculosis and healthy group were not different(p>0.05). 3. The value of NAG activity in tuberculosis had a tendency to be increased according to severity of disease, but that was not significant(p>0.05). The value of NAG activity was increased significantly by use of nephrotoxic antituberculosis drugs(p<0.05). 4. The value of NAG activity in silicosis had a tendecy to be increased according to the size of nodule, use of nephrotoxic antituberculosis drugs and shortness of onset duration, but the increase was not significant(p>0.05). 5. After excluding the users of nephrotoxic antituberculosis drugs, the mean values of NAG activity in healthy control and in tuberculosis control were same as 3.63 U/g creatinine and 3.60 U/g creatinine, respectively. But the mean value of NAG activity in silicosis group was remarkably increased as 10.90 U/g creatinine(p<0.01). As above results, even though there are no abnormal finding in screening renal function test, silicosis can be related with renal dysfunction. And it will be very useful to apply urinary NAG activity in health management of workers exposed to dust.

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Changes in Microflora and Enzyme Activities of Cheonggukjang Prepared with Germinated Soybeans during Fermentation (발아대두 청국장의 발효 중 미생물과 효소활성도의 변화)

  • Oh, Hoon-Il;Eom, Sang-Mi
    • Korean Journal of Food Science and Technology
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    • v.40 no.1
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    • pp.56-62
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    • 2008
  • This study was carried out to investigate the changes in microflora, enzyme activity and sensory quality of four kinds of cheonggukjang during fermentation. Three different kinds of cheonggukjang were prepared with germinated soybeans using rice straw, Bacillus natto, B. natto plus Aspergillus oryzae, and the last one was prepared with non-germinated soybeans using rice straw. The pH values of cheonggukjang prepared with germinated or non-germinated soybeans increased up to 36 hr of fermentation and then decreased. The number of bacteria and molds increased significantly up to 24 hr of fermentation and then leveled off during fermentation. Acidic and neutral protease activities of all cheonggukjang continuously increased significantly during fermentation. ${\alpha}$- and ${\beta}$-Amylase activities of cheonggukjang decreased slightly during fermentation except cheonggukjang prepared with germinated soybeans using the mixed culture. The number of microflora, protease and ${\alpha}$-amylase activities were highest in cheonggukjang prepared with germinated soybeans using B. natto plus A. oryzae. The results of the sensory evaluation revealed that for overall acceptability, the cheonggukjang prepared with germinated soybeans using B. natto plus A. oryzae was similar to the cheonggukjang prepared with non-germinated soybeans using rice straw.