• Title/Summary/Keyword: biological stability

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Caenorhabditis elegans: A Model System for Anti-Cancer Drug Discovery and Therapeutic Target Identification

  • Kobet, Robert A.;Pan, Xiaoping;Zhang, Baohong;Pak, Stephen C.;Asch, Adam S.;Lee, Myon-Hee
    • Biomolecules & Therapeutics
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    • v.22 no.5
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    • pp.371-383
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    • 2014
  • The nematode Caenorhabditis elegans (C. elegans) offers a unique opportunity for biological and basic medical researches due to its genetic tractability and well-defined developmental lineage. It also provides an exceptional model for genetic, molecular, and cellular analysis of human disease-related genes. Recently, C. elegans has been used as an ideal model for the identification and functional analysis of drugs (or small-molecules) in vivo. In this review, we describe conserved oncogenic signaling pathways (Wnt, Notch, and Ras) and their potential roles in the development of cancer stem cells. During C. elegans germline development, these signaling pathways regulate multiple cellular processes such as germline stem cell niche specification, germline stem cell maintenance, and germ cell fate specification. Therefore, the aberrant regulations of these signaling pathways can cause either loss of germline stem cells or overproliferation of a specific cell type, resulting in sterility. This sterility phenotype allows us to identify drugs that can modulate the oncogenic signaling pathways directly or indirectly through a high-throughput screening. Current in vivo or in vitro screening methods are largely focused on the specific core signaling components. However, this phenotype-based screening will identify drugs that possibly target upstream or downstream of core signaling pathways as well as exclude toxic effects. Although phenotype-based drug screening is ideal, the identification of drug targets is a major challenge. We here introduce a new technique, called Drug Affinity Responsive Target Stability (DARTS). This innovative method is able to identify the target of the identified drug. Importantly, signaling pathways and their regulators in C. elegans are highly conserved in most vertebrates, including humans. Therefore, C. elegans will provide a great opportunity to identify therapeutic drugs and their targets, as well as to understand mechanisms underlying the formation of cancer.

Local ridge augmentation using a composite of bone substitute and collagen membrane at peri-implant dehiscence defects: a clinical, radiographic and histological analyses. (성견에서 차단막/골이식재 복합체를 이용한 임플란트 주위 골유도재생 효과: 임상적, 방사선학적, 조직학적 평가)

  • Song, Young Woo;Yoon, So-Ra;Cha, Jae-Kook;Lee, Jung-Seok;Choi, Seong-Ho;Jung, Ui-Won
    • The Journal of the Korean dental association
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    • v.55 no.10
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    • pp.676-687
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    • 2017
  • Objectives : The aim of this study was to evaluate the effects of a composite of bone substitute and collagen barrier membrane (bone patch) for local ridge augmentation at peri-implant dehiscence defects on the clinical efficacy and positional stability in dogs. Materials and methods : Implant placement and ridge augmentation procedure were performed at surgically created peri-implant dehiscence defects in canine mandible (n=6). Four treatment modalities were randomly applied: i) bone patch group, ii) Guided bone regeneration (GBR) without pin fixation group (bone graft and collagen membrane), iii) GBR with pin fixation group, and iv) negative control group. After 12 weeks, clinical, micro-CT and histological analyses were performed. Results : Histologic analysis showed that bone patch group had similar results to GBR group and GBR with fixation group in terms of new bone formation. Micro-CT analysis revealed similar results to histologic analysis in terms of total volume maintenance. Operating time was shorter in bone patch group compared to GBR group and GBR with fixation groups. Conclusions : GBR using bone patch could simplify the ridge augmentation procedure with reduced operating time and equivalent biological performance compared to the conventional procedure.

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14-bp Insertion/Deletion Polymorphism of the HLA-G gene in Breast Cancer among Women from North Western Iran

  • Haghi, Mehdi;Feizi, Mohammad Ali Hosseinpour;Sadeghizadeh, Majid;Lotfi, Abbas Sahebghadam
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.6155-6158
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    • 2015
  • Background: The human leukocyte antigen-G (HLA-G) gene is highly expressed in cancer pathologies and is one strategy used by tumor cells to escape immune surveillance. A 14-bp insertion/deletion (InDel) polymorphism of the HLA-G gene has been suggested to be associated with HLA-G mRNA stability and the expression of HLA-G. The aim of present study was to assess any genetic association between this polymorphism and breast cancer among Iranian-Azeri women. Materials and Methods: In this study 227 women affected with breast cancer, in addition to 255 age-sex and ethnically matched healthy individuals as the control group, participated. Genotyping was performed using polymerase chain reaction and electrophoresis assays. The data were compiled according to the genotype and allele frequencies, compared using the Chi-square test. Statistical significance was set at P<0.05. Results: In this case-control study, no significant difference was found between the case and control groups at allelic and genotype levels, although there is a slightly higher allele frequency of HLA-G 14bp deletion in breast cancer affected group. However,when the stage I subgroup was compared with stage II plus stage III subgroup of affected breast cancer, a significant difference was seen with the 14 bp deletion allele frequency. The stage II-III subgroup patients had higher frequency of deletion allele (57.4% vs 45.8%) than stage I cases (${\chi}^2=4.16$, p-value=0.041). Conclusions: Our data support a possible action of HLA-G 14bp InDel polymorphism as a potential genetic risk factor for progression of breast cancer. This finding highlights the necessity of future studies of this gene to establish the exact role of HLA-G in progression steps of breast cancer.

Development of a Smart Lamp Control Emotion Service using a Biological Algorithm (바이오리듬 분석을 통한 스마트조명 감성제어 서비스 개발)

  • Park, Hyebin;Park, Shinwoo;Cho, Hana;Yoon, Yongik
    • KIISE Transactions on Computing Practices
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    • v.22 no.12
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    • pp.687-692
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    • 2016
  • The advent of Internet of Things(IoT) has increased the need for development of smart life based on Information and Communication Technology(ICT). By using IoT technology, we are able to control connected appliances using smart devices, such as smart phone. To support the smart life, there is a need to utilize emotion information for human behavior, based on both biorhythm and environment information. Research towards this goal suggests a smart lamp control system that has an effect on the human emotion. According to the PSI theory, the control system calculates the biorhythm with an algorithm that uses the human biorhythm, weather factors and walking amounts. The smart lamp works with the recommended color lights that can control the feelings and emotions of the user. Here, we will show the effect of physical and mental stability, health care, and accident prevention.

Suppression of Akt-HIF-1α signaling axis by diacetyl atractylodiol inhibits hypoxia-induced angiogenesis

  • Choi, Sik-Won;Lee, Kwang-Sik;Lee, Jin Hwan;Kang, Hyeon Jung;Lee, Mi Ja;Kim, Hyun Young;Park, Kie-In;Kim, Sun-Lim;Shin, Hye Kyoung;Seo, Woo Duck
    • BMB Reports
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    • v.49 no.9
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    • pp.508-513
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    • 2016
  • Hypoxia-inducible factor (HIF)-1α is a key regulator associated with tumorigenesis, angiogenesis, and metastasis. HIF-1α regulation under hypoxia has been highlighted as a promising therapeutic target in angiogenesis-related diseases. Here, we demonstrate that diacetyl atractylodiol (DAA) from Atractylodes japonica (A. japonica) is a potent HIF-1α inhibitor that inhibits the Akt signaling pathway. DAA dose-dependently inhibited hypoxia-induced HIF-1α and downregulated Akt signaling without affecting the stability of HIF-1α protein. Furthermore, DAA prevented hypoxia-mediated angiogenesis based on in vitro tube formation and in vivo chorioallantoic membrane (CAM) assays. Therefore, DAA might be useful for treatment of hypoxia-related tumorigenesis, including angiogenesis.

Transdermal Permeation Behavior of 5-FU using Microneedle (마이크로니들을 이용한 5-FU의 경피투과 거동)

  • Kim, Myoung-Jin;Park, Jung-Soo;Kim, Yun-Tae;Lee, Jun-Hee;Ahn, Sik-Il;Park, Jong-Hak;Mo, Jong-Hyun;Lee, Tae-Wan;Lee, Han-Koo;Khang, Gil-Son;Lee, Hai-Bang
    • Journal of Pharmaceutical Investigation
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    • v.38 no.1
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    • pp.45-50
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    • 2008
  • 5-Fluorouracil (5-FU) is an antimetabolic of the pyrimidine derivatives that is used in chemotherapy for the treatment of several types of cancer. 5-FU have poor oral absorption and short biological half-time and strong side effects. Microneedle introduced to find a solution of problems. Microneedle device with roll was manufactured for transdermal delivery of various drugs. 5-FU was mixed in non-ionic surfactant such as tween 20 and tween 80. Camscope was used to analysis the permeation magnitude of treated skin by microneedle and trypan blue staining. The 5-FU solution with surfactant measured by ZETA-potential analysis system for stability of solution. The skin permeation rate of 5-FU determined by HPLC. We confirmed that cross treated skin was dyed more deeply than parallel treated skin through trypan blue staining. The results indicate that skin permeation rate of 5-FU was increased with the treatment types and treatment times.

Effect of Ion Pair on Thermostability of F1 Protease: Integration of Computational and Experimental Approaches

  • Rahman, Raja Noor Zaliha Raja Abd;Noor, Noor Dina Muhd;Ibrahim, Noor Azlina;Salleh, Abu Bakar;Basri, Mahiran
    • Journal of Microbiology and Biotechnology
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    • v.22 no.1
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    • pp.34-45
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    • 2012
  • A thermophilic Bacillus stearothermophilus F1 produces an extremely thermostable serine protease. The F1 protease sequence was used to predict its three-dimensional (3D) structure to provide better insights into the relationship between the protein structure and biological function and to identify opportunities for protein engineering. The final model was evaluated to ensure its accuracy using three independent methods: Procheck, Verify3D, and Errat. The predicted 3D structure of F1 protease was compared with the crystal structure of serine proteases from mesophilic bacteria and archaea, and led to the identification of features that were related to protein stabilization. Higher thermostability correlated with an increased number of residues that were involved in ion pairs or networks of ion pairs. Therefore, the mutants W200R and D58S were designed using site-directed mutagenesis to investigate F1 protease stability. The effects of addition and disruption of ion pair networks on the activity and various stabilities of mutant F1 proteases were compared with those of the wild-type F1 protease.

Behavior Analysis of the Treated Femur and Design of Composite Hip Prosthesis (대퇴부 거동 해석 및 복합재료 보철물 설계)

  • 임종완;하성규
    • Journal of Biomedical Engineering Research
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    • v.23 no.2
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    • pp.119-130
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    • 2002
  • The nonlinear finite element program has been developed to analyze the design performance of an artificial hip prosthesis and long term behavior of a treated femur with stems made of composite material after cementless total hip arthroplasty(THA). The authors developed the three dimentional FEM models of femoral bone with designed composite stem which was taken with elliptic cross section of 816 brick elements under hip contact load and muscle farce in simulating single leg stand. Using the program, density changes, stress distributions and micromotions of the material femoral bone were evaluated by changing fiber orientation of stems for selected manufacturing method such as plate cut and bend mold. The results showed that the composite materials such as AS4/PEEK and T300/976 gave less bone resorption than the metallic material such as cobalt chrome alloy, titanium alloy and stainless steal. It was found that increasing the long term stability of the prosthesis in the femur could be obtained by selecting the appropriate ply orientation and stacking sequence of composite.

The Development of Blood Bank Management Program (혈액 은행 전산 처리 프로그램의 개발)

  • Kim, Jong-Won;Lee, Seung-Kuk;Han, Kyou-Sup;Kim, Jin-Q;Cho, Han-Ik;Kim, Sang-In
    • Proceedings of the KOSOMBE Conference
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    • v.1989 no.05
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    • pp.75-76
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    • 1989
  • The blood bank is a field of clinical pathology which requires the most accuratemaintenanceofrecording. Because the mistake in it is directly related to a patient's life. So, the computerization of the blood bank is urgent to maintain a log blook arid to compare the patient's current data with past result. We developed the blood bank management program using 32 bit minicomputer. This is composed of 4 parts; a management of routine test result, special test result, the blood issue and statistics. The management of routine test result handles the patient's information and blood typing and compares above results with the past one of same patient. The management of special test result are for special immunohematologic tests like an irregular antibody, Coombs' test, and etc. Blood issue part records the type of the blood bag, component, and the name of issuer. Statistic part are made to get statistics of each day and each month by the blood type, and the type the blood component. The program is secured by the maintenance of operator's operation history and thu provision of the security code to each operator, without which no one can enter the system and after the content. So the stability and reliability of the data is obtained. This program will be upgraded for bar-code using system in the near future.

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A Study on Changes in Biomechanical Characteristics of the Foot with Respect to Wedge-type Insole Thickness (키높이 인솔두께에 따른 족부의 생체역학적 특성변화에 대한 연구)

  • Park, T.H.;Jung, T.G.;Han, D.W.;Lee, Sung-Jae
    • Journal of Biomedical Engineering Research
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    • v.34 no.2
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    • pp.80-90
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    • 2013
  • Recently, functional insoles of wedge-type it is for the young to raise their height inserted between insole and heel cause foot pain and disease. Additionally, these have a problem with stability and excessively load-bearing during gait like high-heel shoes. In this study, we compared the changes in biomechanical characteristics of foot with different insole thickness then we will utilize for the development of the insole with the purpose of relieving the pain and disease. Subjects(male, n = 6) measured COP(center of pressure) and PCP(peak contact pressure) on the treadmill(140cm/s) using F-scan system and different insole thickness(0~50 mm) between sole and plantar surface during gait. Also, we computed changes of stresses at the foot using finite element model with various insole thickness during toe-off phase. COP moved anterior and medial direction and, PCP was increased at medial forefoot surface, $1^{st}$ and $2^{nd}$ metatarsophalangeal, ($9%{\uparrow}$) with thicker insoles and it was show sensitive increment as the insole thickness was increased from 40 mm to 50 mm. Change of the stress at the soft-tissue of plantar surface, $1^{st}$ metatarsal head represents rapid growth($36%{\uparrow}$). Also, lateral moments were increased over the 100% near the $1^{st}$ metatarsal as the insole thickness was increased from 0 mm to 30 mm. And it is show sensitive increment as the insole thickness changed 10 mm to 20 mm. As a result, it was expected that use of excessively thick insoles might cause unwanted foot pain at the forefoot region. Therefore, insole thickness under 30 mm was selected.