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Compound K attenuates hyperglycemia by enhancing glucagon-like peptide-1 secretion through activating TGR5 via the remodeling of gut microbiota and bile acid metabolism

  • Tian, Fengyuan;Huang, Shuo;Xu, Wangda;Chen, Lan;Su, Jianming;Ni, Haixiang;Feng, Xiaohong;Chen, Jie;Wang, Xi;Huang, Qi
    • Journal of Ginseng Research
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    • v.46 no.6
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    • pp.780-789
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    • 2022
  • Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.

Analysis and Risk Assessment of Benzo(a)pyrene in Edible Oils (식용유지류 중 벤조피렌의 함량 분석 및 안전성 평가)

  • Jang, Mi-Ra;Hong, Mi-Sun;Jung, So-Young;Choi, Bu-Chuhl;Lee, Kyeong-Ah;Kum, Jin-Young;Kim, Il-Young;Kim, Jung-Hun;Chae, Young-Zoo
    • Journal of Food Hygiene and Safety
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    • v.29 no.2
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    • pp.141-145
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    • 2014
  • To assess the health risk for benzo(a)pyrene by the intake of edible oils, 288 cases of edible oils collected from food markets were analysed using the high performance liquid chromatography with fluorescence detector. The levels of benzo(a)pyrene were from non-detection to $4.78{\mu}g/kg$, and the average was $0.11{\mu}g/kg$. The chronic daily exposures of benzo(a)pyrene for total population group and consumer-only group were estimated using the food consumption data in the fifth Korea National Health and Nutrition Examination Survey in 2011. The estimated daily intake of benzo(a)pyrene was $4.26{\times}10^{-3}ng/kg$ b.w./day for total population group and $7.64{\times}10^{-3}ng/kg$ b.w./day for consumer-only group. The MOE (margin of exposure) of benzo(a)pyrene for total population group and consumer-only group was $7.28{\times}10^7{\sim}1.74{\times}10^8$ and $3.95{\times}10^7{\sim}9.42{\times}10^7$, respectively. Accordingly, the health risk from benzo(a)pyrene caused by the intake of edible oils was considered as a very low level.

A Study on Long-term Variations of BOD and COD as Indicators of Organic Matter Pollution in the Han River (한강 본류에서 유기물 오염도 지표인 BOD와 COD에 대한 장기변동 특성)

  • Cho, Hyun-Seok;Kim, Kwang-Rae;Lim, Gyu-Chul;Bae, Kyung-Seok;Lee, Min-Hwan
    • Korean Journal of Ecology and Environment
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    • v.45 no.4
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    • pp.474-481
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    • 2012
  • This study was performed to investigate the degree of long-term pollution at the mainstream of the Han River by comparing the concentration of BOD and COD from 1975 to 2011. The long-term annual average BOD and COD concentration at the mainstream of the Han River showed an increasing trend as it flowed downstream from Paldang Dam to Gayang. The concentration of BOD ($r^2$=0.646) and COD ($r^2$=0.260) showed a consistent decreasing trend for 37 years. In the case of Paldang Dam, BOD has maintained a decreasing trend, whereas the COD value showed an increasing trend after the 1990s. Therefore, a control of non-biodegradable materials in areas around Paldang Dam is required. The result of the seasonal variations of BOD and COD is as follows: spring>winter>summer and fall (p<0.001). The time series analysis revealed a strong correlation for every 12-month period. Also, the amount of water discharge at Paldang Dam has to be systematically controlled because the amount of water discharge from the dam influences the water quality at the mainstream of the Han River.

Effect of Glucose Exposure on the Development of the Mouse Preimplantation Embryo In Vitro (착상전 생쥐배아의 Glucose에 대한 노출이 체외 배발생에 미치는 영향)

  • Kim, Seon-Ui;Eom, Sang-Jun;Yun, San-Hyeon;Im, Jin-Ho;Jeong, Gil-Saeng
    • Korean Journal of Animal Reproduction
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    • v.19 no.3
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    • pp.227-234
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    • 1995
  • This study was carried out to investigate the effects according to the time course of glucose exposure on the development of one-cell embryos beyond morula in CR$_laa$ medium. One-cell zygotes from B6CBA F$_1$ mice were recovered at 24 ~ 25h after hCG and cumulus cells were removed with 0.1% hyaluronidase. The embryos were pooled and subsequently divided into each groups and cultured in CR$_laa$ at 37$^{\circ}C$ in 5% CO$_2$ in aIr. The embryos were either, placed in CR$_laa$ containing various concentration (5.5, 16.5, 27.5 and 38.5 mM) of glucose for 1 min. and subsequently returned to the fresh culture medium (without glucose), or were transferred to the same media containing glucose at 72 h post hCG. The results obtained in these experiments were summarized as follows: 1. The development rates of zygotes, recovered from the oviducts in M2 and cultured in CR$_laa$ with 3mg/Im FAF-BSA, to expanded blastocysts (25.7%) and hatching bIastocysts (17.6%) were significantly higher than those of zygotes recovered in TL Hepes (0% and 0%, respectively). 2. The development rates of one-cell embryos exposed to 27.5 mM glucose at 72 h post hCG for 1 min, were 68.8% (CR$_1$+BSA) a and 77.1% (CR$_1$+FBS) of expanded blastocyst stage, but there were no significant differences between the embryos exposed for 1 min. or transferred at 72 h. 3. Regardless of glucose concentration (5.5, 16.5, 27.5 & 38.5mM), 45.7~61.5% of embryos developed to the blastocyst stage. There were no significant differences between any of the treatments on the devel-opment of one-cell embryos. Therefore, the detrimental effect of highly concentration was not appeared.

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Changes of chemical Composition According to the Ensiling Periods of Total Mixed Fermentation Feeds using Rice Straw and Green Forages (청초와 볏짚을 이용한 완전배합발효사료의 저장기간에 따른 화학조성분의 변화)

  • Lee, H.J.;KIm, W.H.;Kim, H.S.;Lim, K.B.;Ahn, B.S.;Cho, K.K.;Kang, S.H.;Kang, S.K.;Lee, H.G.;Woo, J.H.;Choi, Y.J.
    • Journal of Animal Science and Technology
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    • v.44 no.6
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    • pp.769-782
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    • 2002
  • Three kinds of green forages(rye, oats and mixed forages) was harvested and mixed with rice straw, wheat bran and 2 grains(corn and soybean), which harvested 2 different dates(common harvesting dates, 7 days early to common harvesting dates). And each mixture was ensiled in 6 poly vinyl chlorides that was 60 liter, immediately. They were opened at 0, 5, 10, 25, 35, 60 and 100 days after ensiling for chemical analysis. And its effects of those TMFFs on feed values were observed. Average contents of water, crude protein, ADF, NDF, Ca and P of formulated TMFs were 72 to 75%, 14.75 to 18.24, 12.47 to 19.07, 39.82 to 47.01, 0.99 to 1.07 and 0.38 to respectively. Crude protein content was the highest in the mixed forages-TMFF and the lowest in the rye-TMFF. The ADF and NDF contents of rye-TMFF were higher than orthers. And CP, ADF, NDF, TDN, P and Ca contents were no significant difference among treatments regardless of storage period and harvest time, but all treatments indicated good quality. Intenal temperatures of TMFF were shown to be 1 to 5$^{\circ}C$ higher than ambient temperatures. The temperature of the Oat-TMFF formulated during winter sustained higher to the level of 6${\sim}$9$^{\circ}C$ for 10 days. The pH of TMFF were 4.0 to 4.2 and the content of $NH_3$-N was shown to be 7.79 to 8.23mg/$d{\ell}$. In the VFA contents, any tendency was not shown at all treatments depending on harvest time. Even though rye-TMFF showed the lowest VFA value. At all treatments except rye-TMFF, propionate production was increased and stable after 25 days of storage. Digestibility of rice straw from TMFF on DM basis was 15${\sim}$20% higher compared with non-treated rice straw.

Quality Characteristics of Fermented Alcoholic Beverage with Astragali Radix Added (황기를 첨가한 발효주의 품질 특성)

  • Choi, Ji-Ho;Park, Ji-Hye;Kim, So-Ra;Lee, Choong-Hwan;Park, Shin-Young;Kim, Tack-Joong;Jeong, Seok-Tae;Choi, Han-Seok;Yeo, Soo-Hwan
    • Journal of the East Asian Society of Dietary Life
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    • v.22 no.1
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    • pp.41-51
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    • 2012
  • We produced Hwanggiju (added 0.5~2.0% of ground Astragali Radix compared to starch contents) and investigated the physicochemical characteristics, DPPH free radical scavenging activities, polyphenol contents, and sensory evaluation. For all treatments, the initial pH was 3.9~4.1 and gradually decreased for 6 days from the 1st mashing day, and then rapidly increased to 4.67. As the fermentation proceeded, total acid contents increased in most of the treatments, reduced temporarily after the 2nd mashing time because of the addition of starch material and water, and then slightly rose again. There were little changes in pH and total acid contents followed by adding ground Astragali Radix (AR) to the fermentation periods. Amino acidities of all treatments showed patterns of which consistently rose as the fermentation proceeded and slightly reduced followed by increasing the addition rate of ground AR to the mashes. Soluble solid and alcohol contents also increased continuously and there were few differences among the treatments followed by adding to the ground AR rate. In color, there was no differences in L value, but a and b value showed significant differences by adding ground AR rate. In DPPH free radical scavenging activities, the control (no AR added) showed 53.6% and when grinded AR added, there were improving effects of the activities (0.52~6.9%). In polyphenol contents, the control was 1.05 mg/mL and the ground AR added treatments increased slightly. In the sensory evaluation, the control received a relatively high score ($5.0{\pm}1.0$), and the treatments which added 0.5% ground AR during the 2nd mashing time were also well received ($4.5{\pm}1.3$).

Nitrogen Partitioning at Low Temperature in Fall-Sowing Species II. Distribution to roots, xylem and phloem transport of newly absorbed nitrate (추파 청예작물의 저온 조건하에서 질소의 분배에 관한 연구 II. 흡수된 질산태 질소의 목부, 체관부 및 뿌리로의 전이)

  • Kim, T.H.;Kim, B.H.
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.19 no.1
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    • pp.49-56
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    • 1999
  • With ${15}^N$ labeling under split roots system of winter rye (Secale cereale L.) and forage rape (Brassica napus L.) grown at $5^{\circ}C$ and $25^{\circ}C$, the N flows were respectively quantified to investigate the transport of newly absorbed nitrate-N in whole plant level at low temperature. Comparing with $25^{\circ}C$ culture condition, the total absorbed nitrate-N content at $5^{\circ}C$ decreased to 59.3% and 27.1% in winter rye and forage rape during 9 days. About 2.5% and 7.6 % of nitrate-N were transported into roots, respectively, in winter rye and in forage rape at $25^{\circ}C$. These proportions increased at $5^{\circ}C$ to 3.8% and 10.9%, respectively. Total N contents transferred by xylem in winter rye grown and forage rape grown at $25^{\circ}C$ during were 55.9 and 54.4 mg N/plant, respectively. xylem flows at $5^{\circ}C$ were 60.4% and 28.8% lower than at $25^{\circ}C$ for winter rye and forage rape. These valves represented that averagely 96.8 % and 90.8% of total absorbed nitrate-N were transferred to leaves in winter rye and forage rape during 9 days. Phloem flows were the smallest among other N flows and were much less influenced by temperature treatment for two species examined. About 2.5% and 0.5% of absorbed N were recycled into roots by phloem transport at $25^{\circ}C$, respectively, for winter rye and forage rape. These proportions increased to 5.2% and 0.9% at $5^{\circ}C$.

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Bioequivalence of SCD Zaltoprofen Tablet to Soleton® Tablet (Zaltoprofen 80 mg) (솔레톤 정(잘토프로펜 80 mg)에 대한 삼천당잘토프로펜 정의 생물학적동등성)

  • Kang, Hyun-Ah;Park, Sun-Ae;Kim, Dong-Ho;Kim, Hwan-Ho;Yun, Hwa;Kim, Kyng-Ran;Yoo, Hee-Doo;Park, Eun-Ja;Cho, Hye-Young;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.36 no.3
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    • pp.209-215
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    • 2006
  • Zaltoprofen, (2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid) is an NSAID with powerful anti-inflammatory effects as well as an analgesic action on inflammatory pain. The purpose of the present study was to evaluate the bioequivalence of two zaltoprofen tablets, $Soleton^{\circledR}$ (CJ Corp.) and SCD Zaltoprofen (Samchundang Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of zaltoprofen from the two zatoprofen formulations in vitro was tested using KP Vlll Apparatus ll method with various dissolution media. Twenty six healthy male subjects, $23.2{\pm}2.26$ years in age and$64.7{\pm}8.08$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 80 mg as zaltoprofen was orally administered, blood samples were taken at predetermined time intervals and the concentrations of zaltoprofen in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Soleton^{\circledR}$ were 6.33, 5.91 and 17.7% for $AUC_t$, $C_{max}$ and untransformed $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g.,log $1.01{\sim}1og\;1.11$ and log $0.928{\sim}1og\;1.18$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating SCD Zaltoprofen tablet was bioequivalent to $Soleton^{\circledR}$ tablet.

Quality and Antioxidant Properties of Tofu Coagulated with 'Tsugaru' Apple (Malus domestica Borkh) Juice (쓰가루 사과즙을 이용한 두부의 품질 및 항산화 특성)

  • Kim, Dong-Ho;Hong, Kyeong-Nam;Lim, Yeo-Kyeong;Cha, Seung-Hyeon;Ryu, Ji-Eun;Cho, Jin-Ho;Kim, Dae-Il;Yoo, Do-Il;Jang, Keum-Il
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.8
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    • pp.1130-1137
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    • 2016
  • In this study, we investigated the quality, antioxidant properties, and sensory characteristics of tofu coagulated with 'Tsugaru' apple (Malus domestica Borkh) juice. Yield, $^{\circ}Brix$, pH, total acidity, total polyphenol content, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of 'Tsugaru' apple juice were 60%, 10.3, 3.89, 0.51%, 2.26 mg gallic acid equivalent (GAE)/g, $20{\mu}g$ L-ascorbic acid equivalent (AE)/g, and $75{\mu}g$ AE/g, respectively. In case of Tofu coagulated with 20% (w/v) 'Tsugaru' apple juice, yield, $^{\circ}Brix$, pH, total acidity, hardness, chewiness, cohesiveness, total polyphenol content, ABTS radical scavenging activity, and DPPH radical scavenging activity were 165%, 6.23, 0.27%, 513 g, 315, 0.61, 12.04 mg GAE/g, $80.67{\mu}g$ AE/g, and $92.32{\mu}g$ AE/g, respectively. Both the manufacture yield and pH of tofu decreased with increasing amount of 'Tsugaru' apple juice, whereas total acidity increased. Regarding the texture and chromaticity of tofu coagulated with increasing amounts of 'Tsugaru' apple juice, hardness, chewiness, and a- and b-values increased, whereas cohesiveness and L-value both decreased. In terms of antioxidant activities, total polyphenol content and DPPH radical scavenging activity increased, whereas ABTS radical scavenging activity was maintained within a certain range. Finally, concerning the sensory evaluation (taste, color, flavor, and overall preference) of tofu coagulated with 30% (w/w) 'Tsugaru' apple juice showed the highest scores. Taken together, these results support the possible use of 'Tsugaru' apple juice in producing various foods, as addition of juice enhanced quality, antioxidant properties, and sensory characteristics of tofu.

Combined Therapy of Alfa-Interferon and Thymodulin on Children with Chronic Active Hepatitis B (소아의 B형 만성 활동성 간염에서 저용량 ${\alpha}$-Interferon과 Thymodulin의 병용 치료 효과)

  • Choe, Byung-Ho;Ko, Cheol-Woo
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.1 no.1
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    • pp.79-89
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    • 1998
  • Purpose: Though many antiviral or immunomodulatory agents have been used in patients with chronic HBV hepatitis, interferon is considered to be the only effective therapeutic agent so far. Among immunomodulatory agents, thymodulin, the oral form of thymosin, is currently in clinical trial. We compared the efficacy of alfa-interferon therapy alone with a combined therapy of alfa-interferon and thymodulin in children with chronic active hepatitis B. Method: Twenty three children aged 4.4~13.7 years who were known to be positive for HBsAg and HBeAg in serum for at least 6 months and who had biopsy-proven chronic active hepatitis were given either combined therapy of alfa-interferon and thymodulin or alfa-interferon alone, and all children were HBV DNA positive in their serum at the beginning. Follow-ups have been done for at least 1 year after a 6 month course of therapy and clearance of viral replication markers has been evaluated. Results: 1) During follow up period, 11 (48%) children were seroconverted to anti-HBe and were cleared of HBV DNA from their serum. However, 2 of them relapsed after discontinuance of interferon therapy. 2) Seroconversion occurred more frequently among those who had not been vertically transmitted, had elevated serum ALT levels and low HBV DNA levels before interferon therapy. 3) There was no significant advantage of the combined therapy with thymodulin compared to interferon therapy alone. Conclusion: Combined therapy of alfa-interferon and thymodulin failed to demonstrate synergistic effect. We think that combination therapies of alfa-interferon with other antiviral or immunomodulatory agents need to be studied in order to achieve better therapeutic responses.

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