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Lee, Emerson B.,Jeon, Hyung-Min,Kim, Chang-Ung,Park, Sang M.,Cho, Geunyoung,Kim, Hyun-Jin,Kim, Youngjin,Kim, Doo-Jin,Kim, Young S.,Lee, Hayyoung,Lee, Jie-Oh Elsevier 2019 Nanomedicine Vol.17 No.-
<P><B>Abstract</B></P> <P>Hemagglutinin (HA) displayed on a ferritin nano-cage has been shown to be effective in generating a potent immune response against a broad range of influenza infections. Here, we showed that conjugation of flagellin together with HA to the exterior surface of the ferritin cage greatly enhanced not only the humoral immune response in mice but also antigen-specific T cell responses that include Th1 cytokine secretion. The effect of flagellin remained essentially unchanged when the molar ratio of flagellin to HA was reduced from 1:1 to 1:3. Injection of the ferritin-HA-flagellin cage provided protection against lethal virus challenge in mice. We used a small immunoglobulin fragment V<SUB>L</SUB>12.3 as a convenient method for attaching HA and flagellin to the ferritin cage. This attachment method can be used for rapid screening of a variety of protein cages and nano-assemblies to identify the most suitable carrier and adjuvant proteins for the target antigen.</P> <P><B>Graphical Abstract</B></P> <P>We have shown that a small immunoglobulin fragment, V<SUB>L</SUB>12.3, as a convenient linker can be used for conjugating protein cages, antigens and adjuvants in this study. We showed that influenza hemagglutinin (HA) could be attached to ferritin and an artificial cage protein, I3-01, by this method. We also showed that Protective Antigen (PA) of <I>Bacillus anthracis</I> could be attached to the ferritin cage with high efficiency. We propose that this approach can be used to quickly screen a variety of protein cages and nano-assemblies to identify the best carrier and adjuvant proteins for desired antigens. To demonstrate the usefulness of our V<SUB>L</SUB>12.3 method in the vaccine development, we generated a ferritin-HA-flagellin nano-cage. We discovered that attachment of flagellin together with HA greatly enhanced not only total IgG level but also Th1 cytokine secretion and class switching to IgG2a in mice.</P> <P>[DISPLAY OMISSION]</P>
Evaluation of the Oral Acute Toxicity of Black Ginseng in Rats
Lee, Mi-Ra,Oh, Chang-Jin,Li, Zheng,Li, Jing-Jie,Wang, Chun-Yan,Wang, Zhen,Gu, Li-Juan,Lee, Sang-Hwa,Lee, Jae-Il,Lim, Beong-Ou,Sung, Chang-Keun The Korean Society of Ginseng 2011 Journal of Ginseng Research Vol.35 No.1
We studied the acute oral toxicity of black ginseng (BG) produced by heat process in rats. Single acute BG extract doses of 0, 5, 10, and 15 g/kg dissolved in saline were administered by oral gavage and the animals were kept under observation for 14 days. The single administration of BG extract up to 15 g/kg did not produce mortality, behavioral change or abnormal clinical signs in the rats. These results indicated that the oral $LD_{50}$ of the BG extract in the rats is higher than 15 g/kg. Compared to the control group, no treatment-related biologically significant effects of BG extract were noted in the measurements of the body weight or food intake. At the end of the period, the biochemical parameters and hematological parameters were analyzed in the plasma and blood. A histopathological examination of the liver and kidney was also conducted. Only the blood nitrogen urea and potassium levels in the biochemical indices showed significant differences at 10 and 15 g/kg doses of BG extract compared to the control group. These changes were not considered to be due to the toxicity. None of the other clinical chemistry parameters were affected. Therefore, these results indicate that the BG by heat processing is virtually nontoxic.
Role of the Tumor Suppressor RASSF1A in Mst1-Mediated Apoptosis
Oh, Hyun Jung,Lee, Kyung-Kwon,Song, Su Jung,Jin, Mi Sun,Song, Min Sup,Lee, Joo Hyun,Im, Chang Rak,Lee, Jie-Oh,Yonehara, Shin,Lim, Dae-Sik American Association for Cancer Research 2006 Cancer research Vol.66 No.5
<P>Mammalian sterile 20-like kinase 1 (Mst1) is activated by both caspase-mediated cleavage and phosphorylation in response to apoptotic stimuli, including Fas ligation. Here, we examined the possible role of the tumor suppressor RASSF1A in Mst1 activation and Mst1-mediated apoptosis induced by death receptor signaling. Immunoprecipitation and immunofluorescence analyses revealed that Mst1 was associated with RASSF1A in cultured mammalian cells, with both proteins colocalizing to microtubules throughout the cell cycle. Whereas purified recombinant RASSF1A inhibited the kinase activity of purified recombinant Mst1 in vitro, overexpression of RASSF1A increased the kinase activity of Mst1 in intact cells, suggesting that regulation of Mst1 by RASSF1A in vivo involves more than the simple association of the two proteins. Both the activation of Mst1 and the incidence of apoptosis induced by Fas ligation were markedly reduced in cells depleted of RASSF1A by RNA interference and were increased by restoration of RASSF1A expression in RASSF1A-deficient cells. Moreover, the stimulatory effect of RASSF1A overexpression on Fas-induced apoptosis was inhibited by depletion of Mst1. These findings indicate that RASSF1A facilitates Mst1 activation and thereby promotes apoptosis induced by death receptor signaling.</P>
Lee, Jie-Eun,Kim, Kyoung Min,Kim, Lee-Kyung,Kim, Kyong Young,Oh, Tae Jung,Moon, Jae Hoon,Choi, Sung Hee,Lim, Soo,Kim, Sang Wan,Shin, Chan Soo,Jang, Hak Chul Elsevier 2017 Bone Vol.105 No.-
<P><B>Abstract</B></P> <P>Trabecular bone score (TBS) is a parameter of bone quality that has been shown to be related to vertebral fractures. This study aimed to analyze the difference in discriminatory power of TBS for vertebral fractures according to the bone mineral density (BMD) T-score. Areal BMD at the lumbar spine (LS, L1–L4), femur neck (FN) and total hip were assessed using dual x-ray absorptiometry (Discovery W, Hologic, Bedford, MA) in 929 women aged 50years or older. TBS was analyzed using iNsight software (Med-Imaps, Pessac, France). Vertebral fractures were identified on lateral X-ray films of the thoracic and lumbar spine using a semi-quantitative method. The study subjects consisted of 158 subjects (17.0%) with normal BMD, 461 (49.6%) with osteopenia and 310 (33.4%) with osteoporosis. The incident vertebral fractures were observed in 92 (9.9%) subjects, including 59 fractures in osteoporosis, 29 fractures in osteopenia, and only 4 fractures in normal BMD. We stratified study subjects into two groups according to their BMD T-scores, osteoporosis or osteopenia/normal BMD. The logistic regression model showed that LS BMD values per each 1 standard deviation (SD) decrease were significantly associated with increased risk of vertebral fracture in both osteoporosis and osteopenia/normal BMD group with stronger association in osteoporosis group. However, a TBS value that was lower by 1SD was significantly associated with vertebral fracture risk only in the osteopenia/normal BMD group. The TBS use in addition to FN BMD and age also showed significantly better discriminatory power for vertebral fracture only in the osteopenia/normal BMD group, but not osteoporosis group. In conclusion, TBS is significantly associated with vertebral fractures in subjects with osteopenia/normal BMD levels. Additional assessment of bone microarchitecture using TBS is better able to identify women at risk of fracture, in particular, those with relatively higher BMD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TBS and BMD showed a significant positive correlation and the association becomes stronger as BMD increases. </LI> <LI> TBS could identify women at risk of fracture, in particular, those having relatively higher BMD-osteopenia or normal BMD. </LI> <LI> TBS did not show a significant association with risk of vertebral fractures in subjects having osteoporotic BMD levels. </LI> </UL> </P>
Evaluation of the Oral Acute Toxicity of Black Ginseng in Rats
Mi-Ra Lee,Chang-Jin Oh,Zheng Li,Jing-Jie Li,Chun-Yan Wang,Zhen Wang,Li-Juan Gu,Sang-Hwa Lee,Jae-Il Lee,Beong-Ou Lim,Chang-Keun Sung 고려인삼학회 2011 Journal of Ginseng Research Vol.35 No.1
We studied the acute oral toxicity of black ginseng (BG) produced by heat process in rats. Single acute BG extract doses of 0, 5, 10, and 15 g/㎏ dissolved in saline were administered by oral gavage and the animals were kept under observation for 14 days. The single administration of BG extract up to 15 g/㎏ did not produce mortality, behavioral change or abnormal clinical signs in the rats. These results indicated that the oral LD?? of the BG extract in the rats is higher than 15 g/㎏. Compared to the control group, no treatment-related biologically signifi cant effects of BG extract were noted in the measurements of the body weight or food intake. At the end of the period, the biochemical parameters and hematological parameters were analyzed in the plasma and blood. A histopathological examination of the liver and kidney was also conducted. Only the blood nitrogen urea and potassium levels in the biochemical indices showed signifi cant differences at 10 and 15 g/㎏ doses of BG extract compared to the control group. These changes were not considered to be due to the toxicity. None of the other clinical chemistry parameters were affected. Therefore, these results indicate that the BG by heat processing is virtually nontoxic.
Park Su Hyun,Lee Kang Nyeong,Lee Oh Young,Choi Myung Gyu,Kim Jie-Hyun,Sung In-Kyung,Jang Jae Young,Park Kyung Sik,Chun Hoon Jai,Kim Eun Young,Lee Jun Kyu,Jang Jin Seok,Kim Gwang Ha,Hong Su Jin,Lee Yon 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.2
Background/Aims: Efficacy of proton pump inhibitors is limited in patients with nonerosive reflux disease (NERD). The aim of this study was to comparatively evaluate the efficacy and safety of esomeprazole with sodium bicarbonate and esomeprazole alone. Methods: This was a multicenter, randomized, double-blind, active-controlled, noninferiority comparative study. A total of 379 patients with NERD were randomly allocated to receive either EsoduoⓇ (esomeprazole 20 mg with sodium bicarbonate 800 mg) or NexiumⓇ (esomeprazole 20 mg) once daily for 4 weeks from January 2019 to December 2019. The patients had a history of heartburn for at least 2 days in the week before randomization as well as in the last 3 months and no esophageal mucosal breaks on endoscopy. The primary endpoint was a complete cure of heartburn at week 4. The secondary and exploratory endpoints as well as the safety profiles were compared in the groups at weeks 2 and 4. Results: A total of 355 patients completed the study (180 in the EsoduoⓇ group and 175 in the NexiumⓇ group). The proportions of patients without heartburn in the entire 4th week of treatment were not different between the two groups (33.33% in the EsoduoⓇ group and 35% in the NexiumⓇ group, p=0.737). There were no significant differences in most of the secondary and exploratory endpoints as well as the safety profiles. Conclusions: EsoduoⓇ is as effective and safe as NexiumⓇ for managing typical symptoms in patients with NERD (ClinicalTrial.gov identifier: NCT03928470).