• Title/Summary/Keyword: HIT-T15

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Identification of Anti-Cancer Targets of Eco-Friendly Waste Punica granatum Peel by Dual Reverse Virtual Screening and Binding Analysis

  • Usha, Talambedu;Goyal, Arvind Kumar;Lubna, Syed;Prashanth, H.P.;Mohan, T. Madhan;Pande, Veena;Middha, Sushil Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10345-10350
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    • 2015
  • Background: Punica granatum (family: Lythraceae) is mainly found in Iran, which is considered to be its primary centre of origin. Studies on pomegranate peel have revealed antioxidant, anti-inflammatory, anti-angiogenesis activities, with prevention of premature aging and reducing inflammation. In addition to this it is also useful in treating various diseases like diabetes, maintaining blood pressure and treatment of neoplasms such as prostate and breast cancer. Objectives: In this study we identified anti-cancer targets of active compounds like corilagin (tannins), quercetin (flavonoids) and pseudopelletierine (alkaloids) present in pomegranate peel by employing dual reverse screening and binding analysis. Materials and Methods: The potent targets of the pomegranate peel were annotated by the PharmMapper and ReverseScreen 3D, then compared with targets identified from different Bioassay databases (NPACT and HIT's). Docking was then further employed using AutoDock pyrx and validated through discovery studio for studying molecular interactions. Results: A number of potent anti-cancerous targets were attained from the PharmMapper server according to their fit score and from ReverseScreen 3D server according to decreasing 3D scores. Conclusion: The identified targets now need to be further validated through in vitro and in vivo studies.

Allomyrina Dichotoma Larva Extracts Protect Streptozotocin-induced Oxidative Cytotoxicity (Allomyrina Dichotoma Larva 추출물이 췌장 ${\beta}$-세포에서 streptozotocin에 의해 유도된 산화적 손상에 대한 보호효과)

  • Kim, Deok-Song;Huh, Jin;You, Guen-Chang;Chae, Soo-Chul;Lee, Oh-Sun;Lee, Hwang-Hee Blaise;Lee, Jong-Bin;Kim, Jong-Sun
    • Environmental Analysis Health and Toxicology
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    • v.22 no.4
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    • pp.349-355
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    • 2007
  • 장수풍뎅이 유충(Allomyrina dichotoma larva, ADL)은 중국의 전통 약재로서, 특히 항산화 효과가 우수하여 항당료 제재로 사용되고 있다. 본 연구에서는 이러한 ADL의 추출물을 이용하여 헴스터 췌장의 ${\beta}$-세포(HIT-T15)에서 Streptozotocin에 의해 유발된 산화적 손상에 대한 보호효과 및 그 작용기전을 조사하였다. ADL추출물은 처리농도 의존적으로 Streptozotocin에 의해 유발된 지질과산화 및 세포 내 자유산 소종의 양을 억제함으로서 ${\beta}$-세포의 산화적 스트레스에 의한 손상을 보호하였다. 또한 DNA laddering 방법을 사용하여 Streptozotocin에 의해 유발된 DNA 손상을 조사한 결과, ADL추출물 처리농도에 비례하여 Streptozotocin에 의해 유발된 DNA 손상이 감소하였다. 이러한 산화적 손상의 억제능 관련 작용 기전을 조사하기 위해 DPPH free radical 소거능을 실시하였다. 그 결과 ADL추출물 자체가 DPPH 자유 레디컬 소거능이 있음을 확인하였으며, 또한 플라스미드를 이용한 Single-strand break 방법을 통한 DNA 손상 보호능을 측정한 결과도 $Fe^{3+}$$H_2O_2$에 의해 유발된 DNA 손상이 ADL추출물 처리농도에 비례하여 감소하였다. 이러한 결과들을 종합하여 볼 때, 장수풍뎅이 유충의 추출물들이 자체의 레디컬 소거능 및 산화적 손상에 의한 DNA손상을 억제함으로써, Streptozotocin에 의해 유발된 산화적 손상을 억제할 수 있을 것이라 사료된다.

YH18968, a Novel 1,2,4-Triazolone G-Protein Coupled Receptor 119 Agonist for the Treatment of Type 2 Diabetes Mellitus

  • Han, Taedong;Lee, Byoung Moon;Park, Yoo Hoi;Lee, Dong Hoon;Choi, Hyun Ho;Lee, Taehoon;Kim, Hakwon
    • Biomolecules & Therapeutics
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    • v.26 no.2
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    • pp.201-209
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    • 2018
  • G protein-coupled receptor 119 (GPR119) is expressed in the pancreas and gastrointestinal tract, and its activation promotes insulin secretion in the beta cells of the pancreatic islets as well as the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells, consequently improving glucose-stimulated insulin secretion. Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes. We newly synthesized 1,2,4-triazolone derivatives of GPR119 agonists, which demonstrated excellent outcomes in a cyclic adenosine monophosphate (cAMP) assay. Among the synthesized derivatives, YH18968 showed cAMP=2.8 nM; in GLUTag cell, GLP-1secretion=2.3 fold; in the HIT-T15 cell, and insulin secretion=1.9 fold. Single oral administration of YH18968 improved glucose tolerance and combined treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor augmented the glucose lowering effect as well as the plasma level of active GLP-1 in normal mice. Single oral administration of YH18968 improved glucose tolerance in a diet induced obese mice model. This effect was maintained after repeated dosing for 4 weeks. The results indicate that YH18968 combined with a DPP-4 inhibitor may be an effective therapeutic candidate for the treatment of type 2 diabetes.

A LONGITUDINAL ROENTGENO-CEPHALOMETRIC STUDY ON THE INTERMAXILLARY SPACE OF NORMAL KOREAN CHILDREN AGED FROM 6 TO 11 YEARS (두부방사선 계측사진에 의한 6세에서 11세 사이의 악간 공간에 관한 누년적 연구)

  • Ryu, Young-Kyu
    • The korean journal of orthodontics
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    • v.15 no.1
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    • pp.141-148
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    • 1985
  • It has been a long time since the cephalometrics was introduced to orthodontic field for diagnosis and treatment planning, but it's main concern was limited to hard, skeletodental tissue. It is well known that perioral and facial soft tissue determine the position of individual teeth and that the abnormality in size and shape of the soft tissue are able to cause malformed occlusion. Because of our lack of knowledge about resultant morphologic changes in the relationship between skeletal pattern and specific pattern of lingual and facial muscles, we can't help setting greater value on only abnormalities of teeth in the skeletal interrelationship. In a point of view that the orthodontist is dealing primarily with muscular structures around the dentition, the tongue, lips, and cheeks, therefore it may be desirable to estimate these structure and their potential influence on the dentition on developmental and time base. The author hit upon on idea of the aspect above, so studied on the intermaxillary space and tongue space and this study used the data from cephalometric films of 33 male and 40 female subject aged from 6 to 11 years of normal Korean children following results were obtained: 1. Means and standard deviation of Korean children were obtained. 2. Yearly increment of each variables were obtained. 3. There is the correlationship more than average among the variables except posterior intermaxillary height item. 4. There are differences between male children and female children in all variables except posterior intermaxillary space item. 5. All variables increased as the age increased except posterior intermaxillary height item of male children.

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Inhibitor Design for Human Heat Shock Protein 70 ATPase Domain by Pharmacophore-based in silico Screening

  • Lee, Jee-Young;Jung, Ki-Woong;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • v.29 no.9
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    • pp.1717-1722
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    • 2008
  • The 70 kDa heat-shock protein (Hsp70) involved in various cellular functions, such as protein folding, translocation and degradation, regulates apoptosis in cancer cells. Recently, it has been reported that the green tea flavonoid (−)-epigallocatechin 3-gallate (EGCG) induces apoptosis in numerous cancer cell lines and could inhibit the anti-apoptotic effect of human Hsp70 ATPase domain (hATPase). In the present study, docking model between EGCG and hATPase was determined using automated docking study. Epi-gallo moiety in EGCG participated in hydrogen bonds with side chain of K71 and T204, and has metal chelating interaction with hATPase. Hydroxyl group of catechin moiety also participated in metal chelating hydrogen bond. Gallate moiety had two hydrogen bondings with side chains of E268 and K271, and hydrophobic interaction with Y15. Based on this docking model, we determined two pharmacophore maps consisted of six or seven features, including three or four hydrogen bonding acceptors, two hydrogen bonding donors, and one lipophilic. We searched a flavonoid database including 23 naturally occurring flavonoids and 10 polyphenolic flavonoids with two maps, and myricetin and GC were hit by map I. Three hydroxyl groups of B-ring in myricetin and gallo moiety of GC formed important hydrogen bonds with hATPase. 7-OH of A-ring in myricetin and OH group of catechin moiety in GC are hydrogen bond donors similar to gallate moiety in EGCG. From these results, it can be proposed that myricetin and GC can be potent inhibitors of hATPase. This study will be helpful to understand the mechanism of inhibition of hATPase by EGCG and give insights to develop potent inhibitors of hATPase.

Career Choice and Employment Preparation Condition for EMT Students (응급구조(학)과 학생의 취업진로선택 및 취업준비 현황)

  • Park, So-Mi;Choi, Eun-Sook;Kim, Mi-Sook;Lee, Kyoung-Youl
    • The Korean Journal of Emergency Medical Services
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    • v.15 no.1
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    • pp.65-78
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    • 2011
  • Purpose : We investigated the career choice and the employment preparation of emergency medical technology (EMT) students. The results of study will provide the base information about the consciousness for career choice and employment of the EMT students. Method : We conducted 1,586 surveys from 665 students at six four-year colleges and 921 students at seven three-year colleges, from Aug. 27th to Oct. 31st in 2010. The result was analyzed by SPSS 18.0 using description statistics, t-test, ANOVA, Scheffe and Pearson correlation coefficient. Result : The general characteristics showed male 50.2% and female 49.8%, and first grade 34.6%, second grade 27.4%, third grade 28.2%, and fourth grade 9.8%. The 53.9% of students had experienced the hospital training and the 44.8% did the fire station training. For the choice of job, there were the 61.8% student who hope to enter the employ in fire station or public service, while 25.7% students hope to be employed in hospitals. The reason for a wish job were 'majors-related job' in 18.2% students, 'employment stability' in 17.2% and 'hit on the aptitude and talent' in 16.7%, 'appropriate salaries' in 15.9%. In the questionnaire of the University what to assist you for job preparation, they chose the 'support for get major related license', 'support for officer exam preparation' and 'support of foreign language study' in 34.6%, 16.8% and 16.6%, respectively. For achieved licence, they had a driver's license in 53.9%, BLS (basic life support) provider in 20.3%, life guard in 16.2% and scuba in 8.8%. The statistically significant correlation was identified between the awareness of University that provides job information and one's career awareness (r= .203, p<.000), the awareness that University provide job information and one's confidence in employment (r= .236, p<.000), and one's career awareness and one's confidence in employment (r = .356, p = .000). Conclusion : The most of EMT Students are well conscious of the their future employment and has prepared career to be employed their preference job.

Study of perception of the visual depth caused by the color correction (입체영상 제작에서 색 보정 결과가 입체감 인지에 미치는 영향 연구)

  • Han, Myung-Hee;Kim, Chee-Yong
    • Journal of Digital Contents Society
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    • v.11 no.2
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    • pp.177-184
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    • 2010
  • These days, as digital producing technique has been developed, 3D imaging technique is used in high-tech computer and T.V. Also study for 3D producing technique is actively in progress. Moreover, as James Cameron's movie, 'Avatar' released in 2009 was a box office hit, the issue about 3D image came to the fore again. At this point, I decided to study the effect of the visual depth caused by the color correction during the post-production stage. The purpose of this study is to offer information about processing effective images through data about the effect of the visual depth that applies the color correction during the post-production stage. Basically, I supposed that color and contract would have effects on depth of 3D image. As a result, I could find out the changes of visual depth, space perception and sense of depth throughout the experiment. Applying this result,, I produced the 15 minutes of 3D advertisement movie and I found out that the color correction during the post-production stage was very effective for 3D depth. The left image and the right image by beam splitter based rig and parallel rig were used for this study. Also I adjusted the strong contrast by the color correction during the post-production stage after correcting convergence and visual depth during editing. As a result, I could produce images which had strong sense of space and sense of depth.

Anti-diabetic Effects of Banaba Leaf Extracts (Lagerstroemia speciosa Pers.) through Solvents (추출용매 변화에 따른 바나바(Lagerstroemia speciosa Pers.) 잎 추출물의 항당뇨 효과)

  • Kim, Kyun-Ha;Roh, Sang-Geun;Li, Chun-Ri;Jin, Chun-Feng;Kim, Andre;Choi, Won-Chul
    • Journal of Life Science
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    • v.18 no.9
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    • pp.1305-1311
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    • 2008
  • This study investigated that the antidiabetic effects of banaba extracts with variety solvents selectivity in vitro and in vivo. Banaba extracts were prepared with water, 70% ethanol, 90% ethanol, 100% ethanol and water-ethanol that of extract twice times sequentially water and ethanol. Cell toxicity and insulin secretion of banaba extracts was tested by MTT (3-[4,5-dimetylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay on hamster insulinoma cell line, HIT-T15. Also we tested that insulin, body weight, blood glucose, total cholesterol, HDL-cholesterol, triglyceride and free fatty acid in streptozotocin diabetic rats. Water-ethanol extract has remarkable antidiabetic effect compare with the other banaba extracts. For water-ethanol extract has both of hydrophilic and hydrophobic antidiabetic materials from banaba. Expecially, corosolic acid, as known as unique polyphenol, has antidiabetic effect studied by many researchers till nowadays. But corosolic acid does not solve in water. Otherwise, we suggest that banaba extract of hydrophilic and hydrophobic materials (polyphenol and antioxidants) mixture more increased antidiabetic effects.

Evolutionary Explanation for Beauveria bassiana Being a Potent Biological Control Agent Against Agricultural Pests

  • Han, Jae-Gu
    • 한국균학회소식:학술대회논문집
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    • 2014.05a
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    • pp.27-28
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    • 2014
  • Beauveria bassiana (Cordycipitaceae, Hypocreales, Ascomycota) is an anamorphic fungus having a potential to be used as a biological control agent because it parasitizes a wide range of arthropod hosts including termites, aphids, beetles and many other insects. A number of bioactive secondary metabolites (SMs) have been isolated from B. bassiana and functionally verified. Among them, beauvericin and bassianolide are cyclic depsipeptides with antibiotic and insecticidal effects belonging to the enniatin family. Non-ribosomal peptide synthetases (NRPSs) play a crucial role in the synthesis of these secondary metabolites. NRPSs are modularly organized multienzyme complexes in which each module is responsible for the elongation of proteinogenic and non-protein amino acids, as well as carboxyl and hydroxyacids. A minimum of three domains are necessary for one NRPS elongation module: an adenylation (A) domain for substrate recognition and activation; a tholation (T) domain that tethers the growing peptide chain and the incoming aminoacyl unit; and a condensation (C) domain to catalyze peptide bond formation. Some of the optional domains include epimerization (E), heterocyclization (Cy) and oxidation (Ox) domains, which may modify the enzyme-bound precursors or intermediates. In the present study, we analyzed genomes of B. bassiana and its allied species in Hypocreales to verify the distribution of NRPS-encoding genes involving biosynthesis of beauvericin and bassianolide, and to unveil the evolutionary processes of the gene clusters. Initially, we retrieved completely or partially assembled genomic sequences of fungal species belonging to Hypocreales from public databases. SM biosynthesizing genes were predicted from the selected genomes using antiSMASH program. Adenylation (A) domains were extracted from the predicted NRPS, NRPS-like and NRPS-PKS hybrid genes, and used them to construct a phylogenetic tree. Based on the preliminary results of SM biosynthetic gene prediction in B. bassiana, we analyzed the conserved gene orders of beauvericin and bassianolide biosynthetic gene clusters among the hypocrealean fungi. Reciprocal best blast hit (RBH) approach was performed to identify the regions orthologous to the biosynthetic gene cluster in the selected fungal genomes. A clear recombination pattern was recognized in the inferred A-domain tree in which A-domains in the 1st and 2nd modules of beauvericin and bassianolide synthetases were grouped in CYCLO and EAS clades, respectively, suggesting that two modules of each synthetase have evolved independently. In addition, inferred topologies were congruent with the species phylogeny of Cordycipitaceae, indicating that the gene fusion event have occurred before the species divergence. Beauvericin and bassianolide synthetases turned out to possess identical domain organization as C-A-T-C-A-NM-T-T-C. We also predicted precursors of beauvericin and bassianolide synthetases based on the extracted signature residues in A-domain core motifs. The result showed that the A-domains in the 1st module of both synthetases select D-2-hydroxyisovalerate (D-Hiv), while A-domains in the 2nd modules specifically activate L-phenylalanine (Phe) in beauvericin synthetase and leucine (Leu) in bassianolide synthetase. antiSMASH ver. 2.0 predicted 15 genes in the beauvericin biosynthetic gene cluster of the B. bassiana genome dispersed across a total length of approximately 50kb. The beauvericin biosynthetic gene cluster contains beauvericin synthetase as well as kivr gene encoding NADPH-dependent ketoisovalerate reductase which is necessary to convert 2-ketoisovalarate to D-Hiv and a gene encoding a putative Gal4-like transcriptional regulator. Our syntenic comparison showed that species in Cordycipitaceae have almost conserved beauvericin biosynthetic gene cluster although the gene order and direction were sometimes variable. It is intriguing that there is no region orthologous to beauvericin synthetase gene in Cordyceps militaris genome. It is likely that beauvericin synthetase was present in common ancestor of Cordycipitaceae but selective gene loss has occurred in several species including C. militaris. Putative bassianolide biosynthetic gene cluster consisted of 16 genes including bassianolide synthetase, cytochrome P450 monooxygenase, and putative Gal4-like transcriptional regulator genes. Our synteny analysis found that only B. bassiana possessed a bassianolide synthetase gene among the studied fungi. This result is consistent with the groupings in A-domain tree in which bassianolide synthetase gene found in B. bassiana was not grouped with NRPS genes predicted in other species. We hypothesized that bassianolide biosynthesizing cluster genes in B. bassiana are possibly acquired by horizontal gene transfer (HGT) from distantly related fungi. The present study showed that B. bassiana is the only species capable of producing both beauvericin and bassianolide. This property led to B. bassiana infect multiple hosts and to be a potential biological control agent against agricultural pests.

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