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Docking Study of Biflavonoids, Allosteric Inhibitors of Protein Tyrosine Phosphatase 1B

  • Lee, Jee-Young;Jung, Ki-Woong;Woo, Eun-Rhan;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • 제29권8호
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    • pp.1479-1484
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    • 2008
  • Protein tyrosine phosphatase (PTP) 1B is the superfamily of PTPs and a negative regulator of multiple receptor tyrosine kinases (RTKs). Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a strategy for the treatment of type 2 diabetes and obesity. Recently, it has been reported that amentoflavone, a biflavonoid extracted from Selaginella tamariscina, inhibited PTP1B. In the present study, docking model between amentoflavone and PTP1B was determined using automated docking study. Based on this docking model and the interactions between the known inhibitors and PTP1B, we determined multiple pharmacophore maps which consisted of five features, two hydrogen bonding acceptors, two hydrogen bonding donors, and one lipophilic. Using receptor-oriented pharmacophore-based in silico screening, we searched the biflavonoid database including 40 naturally occurring biflavonoids. From these results, it can be proposed that two biflavonoids, sumaflavone and tetrahydroamentoflavone can be potent allosteric inhibitors, and the linkage at 5',8''-position of two flavones and a hydroxyl group at 4'-position are the critical factors for their allosteric inhibition. This study will be helpful to understand the mechanism of allosteric inhibition of PTP1B by biflavonoids and give insights to develop potent inhibitors of PTP1B.

소아 서혜부탈장 진단에 초음파검사 실시 후 임상 양상의 변화 (A Clinical Study of Pediatric Inguinal Hernia Before and After Using Ultrasonography for Diagnosis)

  • 이정은;최금자
    • Advances in pediatric surgery
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    • 제10권2호
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    • pp.131-135
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    • 2004
  • The purpose of this retrospective study was to evaluate the effects of diagnostic sonography in pediatric patients with inguinal hernias. The patients were classified into two groups. Group A included the patients who had been operated upon for inguinal hernia in 1980's, when diagnostic sonography was not available. Group B included the patients, operated upon for inguinal hernia from 2001 to 2002, when inguinal sonography was employed to detect potential bilateral hernias. The age distribution, sex ratio, laterality, bilaterality, and concomitant symptoms were compared between group A and group B. There were 296 cases in group A and 377 cases in group B. The prevalent age group was from 1 to 5 years. There was no difference in age group distribution between both groups. The male to female ratio was 5.3:1 in group A and 3.5:1 in group B. The ratio of unilateral to bilateral hernia was 5:1 in group A and 3:1 in group B. In cases with a unilateral hernia, the ratio of right to left was 1.5:1 in group A and 1.8:1 in group B. In cases with bilateral hernia, the simultaneous bilateral hernia was 33 cases (67.4 %) in group A and 75 cases (80.6 %) in group B. The sequential bilateral hernia was 16 cases (32.7 %) in group A and 18 cases (19.4 %) in group B. Although the ratio of bilateral hernia was increased in group B, the portion of the sequential bilateral hernia was significantly decreased in group B. In conclusion, there were no differences in the age distribution and the laterality between group A and B. The ratio of female patients and the incidence of bilateral hernia were increased in group B even though the portion of the sequential bilateral hernia was decreased. This result shows that the preoperative inguinal sonography in unilateral hernia with potential bilateral hernia is useful in early detection of the sequential contralateral hernia.

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인삼(人蔘)의 잎(葉) 또는 줄기(莖) 첨가급식(添加給食)에 의(依)한 식이(食餌)의 영양효과(營養效果) 연구(硏究) (A Study on Nutritional effects of Rat diet by Supplementing with Leaf or Trunk of Panax Ginseng)

  • 이서형;황우익
    • Journal of Nutrition and Health
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    • 제12권2호
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    • pp.37-44
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    • 1979
  • Korea has produced large quantities of Panax Ginseng roots which have a stimulating effect on the metabolisma of protein, lipid and nucleic acids in the body. Authors believe that the lear and trunk of Panax Ginseng might have some components possessing a similar activity to Panax Ginseng root although the quantity and quality of the functional components may be somewhat different. Therefore, this study was designed to observe the nutritional effects of diet supplemented with the leaves or trunks of Panax Ginseng. Weanling(body weight; $82{\pm}3g$) male albino rats were subjected to six different dietary groups as followings; A groups; dietary groups which were treated with steam for 30 min at $115^{\circ}C}$. B Groups; dietary groups which were not treated with steam. A-C (or B-C) dietary group; Control for A groups(or B groups) containing 99% wheat flour. A-1 (or B-1) dietary group; dietary group supplemented with 2% leaf of Panax Ginseng, which replaced 2% wheat flour of control diet. A-2 (or B-2) dietary group; dietary group supplemented with 2% trunk of Panax Ginseng, which replaced 2% wheat flour or control diet. Each group of rats was maintained with the corresponding diet for 40 days. And then they were sacrificed. The growth rate, protein efficiency ratio, and the contents of lipid and cholesterol in organs were determined. The results obtained are summarized as follows;1) The gained body weights of dietary group supplemented with 2% leaf(A-1 and B-1) or 2% trunk(A-2 and B-2) of panax Ginseng were more increased in comparison to the corresponding control group(A-C and B-C). 2) The gained body weight of each group in A-group(A-C, A-I and A-2) was higher than that or each corresponding dietary group in B-group(B-C, B-1 and B-2). 3) The protein efficiency ratios of A-1 and A-2 dietary group, and B-1 and B-2 dietary group were more improved in comparison to the corresponding control group(A-C and B­C). 4) The lipid contents in the liver of A-1 and B-1 dietary groups were lower than in that of A-C and. B-C dietary group, respectively. According to the above results, it could be suggested that the nutritional value of the wheat flour can be improved by supplement of 2% leaf or 2% trunk of Panax Ginseng.

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Constituents of the Herb of Isodon excisus var. coreanus

  • Kim, Ho-Kyoung;Whang, Wan-Kyunn;Kim, Il-Hyuk
    • Archives of Pharmacal Research
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    • 제20권3호
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    • pp.291-296
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    • 1997
  • The studies were carried out to evaluate the constituents in the aerial part of Isodon excisus var. coreanus (Labiatae). From the aqueous fraction of methanol extract, compound I (${\alpha}$-[[3-(3, 4-dihydroxyphenyl)-1-oxo-2-propenyl]oxy]-3,4-dihydroxy-benzenepropanoic acid), compound II (9-methyl-dihydroferulic acid-4-O-.betha.-D-glucopyranosyl $(1{\rightarrow}2)$-${\alpha}$-L- rhamnopyranosyl (1.rarw.4)-.betha.-D-glucopyranoside), compound III (ent-7.alpha., 11${\alpha}$,15.betha.-trihydroxy-kaur-16-en-1-O-.betha.-D-glucopyranoside) and compound IV ($2{\alpha}$,3${\beta}$,$7{\alpha}$,23-tetrahydroxy-olean-12 -en-28-oic acid 28-O-${\beta}$-D-glucopyranoside) were isolated and identified on the basis of their physicochemical and spectroscopic evidences[IR, FAB(-)MS,$^{1}H-NMR,$$^{13}C-NMR,$$ HMQC$$^{1}H-^{1}H $COSY and HMBC (Heteronuclear Multiple Bond Connectivity)]. Especially, New compounds II and III were named Isodonin A and Isodonin B respectively.

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Root Colonization and ISR-mediated Anthracnose Disease Control in Cucumber by Strain Enterobacter asburiae B1

  • Bharathkumar, S.;Park, Jin-Woo;Han, Ji-Hee;Park, Kyung-Seok
    • The Plant Pathology Journal
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    • 제25권4호
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    • pp.333-343
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    • 2009
  • Here, we show that an endophytic bacterial strain, Enterobacter asburiae B1 exhibits the ability to elicit ISR in cucumber, tobacco and Arabidopsis thaliana. This indicates that strain B1 has a widespread ability to elicit ISR on various host plants. In this study, E. asburiae strain B1 did not show antifungal activity against tested major fungal pathogens, Colletotrichum orbiculare, Botrytis cinerea, Phytophthora capsici, Rhizoctonia solani, and Fusarium oxysporum. Moreover, the siderophore production by E. asburiae strain B1 was observed under in vitro condition. In greenhouse experiments, the root treatment of strain B1 significantly reduced disease severity of cucumber anthracnose caused by fungal pathogen C. orbiculare compared to nontreated control plants. By root treatment of strain B1 more than 50% disease control against anthracnose on cucumber was observed in all greenhouse experiments. Simultaneously, under the greenhouse condition, the soil drench of strain B1 and a chemical inducer benzothiadiazole (BTH) to tobacco plants induced GUS activity which is linked with activation of PR promoter gene. Furthermore, in Arabidopsis thaliana plants the soil drench of strain B1 induced the defense gene expression of PR1 and PDF1.2 related to salicylic acid and jasmonic acid/ethylene signaling pathways, respectively. In this study, for the main focus on root colonization by strain B1 associated with defense responses, bacterial cells of strain B1 was tagged with the gfp gene encoding the green fluorescent protein in order to determine the colonization pattern of strain B1 in cucumber. The gfp-tagged B1 cells were found on root surface and internal colonization in root, stem, and leaf. In addition to this, the scanning electron microscopy observation showed that E. asburiae strain B1 was able to colonized cucumber root surface.

MiR-133b Acts as a Tumor Suppressor and Negatively Regulates TBPL1 in Colorectal Cancer Cells

  • Xiang, Kai-Min;Li, Xiao-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권8호
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    • pp.3767-3772
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    • 2014
  • Introduction: MicroRNAs have emerged as post-transcriptional regulators that are critically involved in tumorigenesis. This study was designed to explore the effect of miRNA 133b on the proliferation and expression of TBPL1 in colon cancer cells. Methods: Human colon cancer SW-620 cells and human colon adenocarcinoma HT-29 cells were cultured. MiRNA 133b mimcs, miRNA 133b inhibitors, siRNA for TBPL1 and scrambled control were synthesized and transfected into cells. MiR-133b levels in cells and CRC tumor tissue was measured by real-time PCR. TBPL1 mRNA was detected by RT-PCR. Cell proliferation was studied with MTT assay. Western blotting was applied to detect TBPL1 protein levels. Luciferase assays were conducted using a pGL3-promoter vector cloned with full length of 3'UTR of human TBPL1 or 3'UTR with mutant sequence of miR-133b target site in order to confirm if the putative binding site is responsible for the negative regulation of TBPL1 by miR-133b. Results: Real time PCR results showed that miRNA 133b was lower in CRC tissue than that in adjacent tissue. After miR-133b transfection, its level was elevated till 48h, accompanied by lower proliferation in both SW-620 and HT-29 cells. According to that listed in http://www.targetscan.org, the 3'-UTR of TBPL1 mRNA (NM_004865) contains one putative binding site of miR-133b. This site was confirmed to be responsible for the negative regulation by miR-133b with luciferase assay. Further, Western blotting and immunohistochemistry both indicated a higher TBPL1 protein expression level in CRC tissue. Finally, a siRNA for TBPL1 transfection obviously slowed down the cell proliferation in both SW-620 and HT-29 cells. Conclusion: MiR-133b might act as a tumor suppressor and negatively regulate TBPL1 in CRC.

TABLES OF D-CLASSES IN THE SEMIGROUP $B_n1$ OF THE BINARY RELATIONS ON A SET X WITH n-ELEMENTS

  • Kim, Jin-Bai
    • 대한수학회보
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    • 제20권1호
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    • pp.9-13
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    • 1983
  • M$_{n}$(F) denotes the set of all n*n matrices over F={0, 1}. For a, b.mem.F, define a+b=max{a, b} and ab=min{a, b}. Under these operations a+b and ab, M$_{n}$(F) forms a multiplicative semigroup (see [1], [4]) and we call it the semigroup of the n*n boolean matrices over F={0, 1}. Since the semigroup M$_{n}$(F) is the matrix representation of the semigroup B$_{n}$ of the binary relations on the set X with n elements, we may identify M$_{n}$(F) with B$_{n}$ for finding all D-classes.l D-classes.

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Defective Anks1a disrupts the export of receptor tyrosine kinases from the endoplasmic reticulum

  • Park, Soochul
    • BMB Reports
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    • 제49권12호
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    • pp.651-652
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    • 2016
  • EphA2 has been implicated in amplifying ErbB2 tumorigenic signaling. One protein that interacts with EphA2 is the Anks1a PTB adaptor. However, the precise role of Anks1a in EphA2-mediated tumorigenesis is unclear. We demonstrated that Anks1a localizes to the ER upon phosphorylation and that the Ankyrin repeats and PTB of Anks1a bind to EphA2 and Sec23, respectively. Thus, Anks1a facilitates the selective packaging of EphA2 into COPII vesicles. Additionally, Anks1a knockout mice, a phenocopy of EphA2 knockout mice, exhibited markedly reduced ErbB2-induced breast tumorigenesis. Strikingly, ErbB2 did not localize to the cell surface following Anks1a knockdown in primary mammary tumor cells over-expressing ErbB2. Importantly, EphA2 was critical for stabilizing ErbB2 through complex formation, but its interaction with Anks1a also facilitated ErbB2 loading into COPII carriers. These findings suggest a novel role for Anks1a in the molecular pathogenesis of breast tumors and possibly other human diseases.

Geometric Means of Positive Operators

  • Nakamura, Noboru
    • Kyungpook Mathematical Journal
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    • 제49권1호
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    • pp.167-181
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    • 2009
  • Based on Ricatti equation $XA^{-1}X=B$ for two (positive invertible) operators A and B which has the geometric mean $A{\sharp}B$ as its solution, we consider a cubic equation $X(A{\sharp}B)^{-1}X(A{\sharp}B)^{-1}X=C$ for A, B and C. The solution X = $(A{\sharp}B){\sharp}_{\frac{1}{3}}C$ is a candidate of the geometric mean of the three operators. However, this solution is not invariant under permutation unlike the geometric mean of two operators. To supply the lack of the property, we adopt a limiting process due to Ando-Li-Mathias. We define reasonable geometric means of k operators for all integers $k{\geq}2$ by induction. For three positive operators, in particular, we define the weighted geometric mean as an extension of that of two operators.

Bacillus subtilis와 Bacillus megaterium에서의 $\beta$-1,3-glucanase 유전자의 발현 (Expression of a $\beta$-1,3-Glucanase Gene from Bacillus circulans in B. subtilis and B. megaterium)

  • 김기훈;김지연;김한복;이동석
    • 미생물학회지
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    • 제37권4호
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    • pp.253-258
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    • 2001
  • Bacillus circulans KCT3004 기원의 $\beta$-1,3-glucanase 유전자를 함유한 재조합 플라스미드 pLM460과 pUB110을 이용하여 shuttle 플라스미드 pMLS1180을 제작하고 Bacillus 세포에 이동.발현시켰다. pLMS1180으로 형질전환된 B. subtilis와 B. megaterium은 효율적으로 $\beta$-1,3-glucanase를 생산하였고, 이 효소들은 세포의 증식과 비례하여 생산되었다. 형질전환체가 생산하는 $\beta$-1,3-glucanase의 최대 활성을 유전자 공여 균주인 B. circulans와 비교하여 보니, B. subtilis는 14배, B. megaterium은 5배 정도의 높은 활성을 나타내었다. 그리고 대장균 형질전환체는 분비율이 7% 정도인데 반하여 B. subtilis 형질전환체는 생산된 효소를 전부, B. megaterium 형질전환체는 약 97%를 세포 외로 분비하는 것을 알 수 있었다. SDS-PAGE를 통해 대장균과 B. subtilis, B. megaterium에서 발현된 효소의 분자량을 분석해 보니 약 38,000으로 추정되었다. 또한, 이들 형질전환체가 생산하는 $\beta$-1,3-glucanase는 laminarin에 작용하여 주된 산물로서 laminaribiose (G2), laminaritriose (G3) 이상의 다양한 laminarioligosaccharide들을 생산함이 확인되었다. pLMS1180의 각 숙주 내에서이 안정성을 살펴본 결과 B.megaterium에서는 88%, 대장균에서는 75%, B. subtilis에서는 48%로 나타났다.

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