• Title/Summary/Keyword: Analogs

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The Metabolic Effects of FGF21: From Physiology to Pharmacology (생리, 약학적 관점에서 fibroblast growth factor 21 (FGF21)의 대사 효과 고찰)

  • Song, Parkyong
    • Journal of Life Science
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    • v.30 no.7
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    • pp.640-650
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    • 2020
  • Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF protein family which is highly synthesized in the liver, pancreas, and adipose tissue. Depending on the expression tissue, FGF21 uses endo- or paracrine features to regulate several metabolic pathways including glucose metabolism and energy homeostasis. Different physiologically stressful conditions such as starvation, a ketogenic diet, extreme cold, and mitochondrial dysfunction are known to induce FGF21 synthesis in various tissues to exert either adaptive or defensive mechanisms. More specifically, peroxisome proliferator-activated receptor gamma and peroxisome proliferator-activated receptor alpha control FGF21 expression in adipose tissue and liver, respectively. In addition, the pharmacologic administration of FGF21 has been reported to decrease the body weight and improve the insulin sensitivity and lipoprotein profiles of obese mice and type 2 diabetes patients meaning that FGF21 has attracted huge interest as a therapeutic agent for type 2 diabetes, obesity, and non-alcoholic fatty liver disease. However, understanding FGF21 remains complicated due to the paradoxical condition of its tissue-dependent expression. For example, nutrient deprivation largely increases hepatic FGF21 levels whereas adipose tissue-derived FGF21 is increased under feeding condition. This review discusses the issues of interest that have arisen from existing publications, including the tissue-specific function of FGF21 and its action mechanism. We also summarize the current stage of a clinical trial using several FGF21 analogs.

The Characteristics of Lessons Using Analogies Planned by Pre-service Science Teachers (예비과학교사가 계획한 비유 사용 수업의 특징)

  • Kim, Minhwan;Kim, Hyeree;Noh, Taehee
    • Journal of the Korean Chemical Society
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    • v.62 no.2
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    • pp.148-158
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    • 2018
  • In this study, we investigated the characteristics of planning lessons using analogies by pre-service science teachers. Eight pre-service teachers at a college of education in Seoul participated in this study. After the workshop of instructional analogies in science education, they planned lessons using analogies. We also conducted semi-structured interviews. For the analyses, we used a revised framework from a previous work which characterized the dimensions of teaching through analogies. The analyses of the results revealed that most pre-service teachers planned to use analogies in beginning or developing lesson and to present analogs before target concepts. The degree of activity allowed for students was not high. Many did not recognize the necessity of assessment and did not include assessment in planning lessons. They planned clarified mapping strategies which are teacher-centered and also not to cover unshared attributes and multiple analogies, because they thought that students could misunderstand mapping and unshared attributes could make students confused. Most planned to use figures, pictures, and videos to help students understand analogies that they presented. Educational implications of these findings are discussed.

PRIP, a Novel Ins(1,4,5)P3 Binding Protein, Functional Significance in Ca2+ Signaling and Extension to Neuroscience and Beyond

  • Kanematsu, Takashi;Takeuchi, Hiroshi;Terunuma, Miho;Hirata, Masato
    • Molecules and Cells
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    • v.20 no.3
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    • pp.305-314
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    • 2005
  • Investigation of chemically synthesized inositol 1,4,5-trisphosphate [$Ins(1,4,5)P_3$] analogs has led to the isolation of a novel binding protein with a molecular size of 130 kDa, characterized as a molecule with similar domain organization to phospholipase C-${\delta}1$ (PLC-${\delta}1$) but lacking the enzymatic activity. An isoform of the molecule was subsequently identified, and these molecules have been named PRIP (PLC-related, but catalytically inactive protein), with the two isoforms named PRIP-1 and -2. Regarding its ability to bind $Ins(1,4,5)P_3$ via the pleckstrin homology domain, the involvement of PRIP-1 in $Ins(1,4,5)P_3$-mediated $Ca^{2+}$ signaling was examined using COS-1 cells overexpressing PRIP-1 and cultured neurons prepared from PRIP-1 knock-out mice. Yeast two hybrid screening of a brain cDNA library using a unique N-terminus as bait identified GABARAP ($GABA_A$ receptor associated protein) and PP1 (protein phosphatase 1), which led us to examine the possible involvement of PRIP in $GABA_A$ receptor signaling. For this purpose PRIP knock-out mice were analyzed for $GABA_A$ receptor function in relation to the action of benzodiazepines from the electrophysiological and behavioral aspects. During the course of these experiments we found that PRIP also binds to the b-subunit of $GABA_A$ receptors and PP2A (protein phosphtase 2A). Here, we summarize how PRIP is involved in $Ins(1,4,5)P_3$-mediated $Ca^{2+}$ signaling and $GABA_A$ receptor signaling based on the characteristics of binding molecules.

An Enzyme-Linked Immunosorbent Assay for $Aflatoxin\;M_1$ in Cow's Milk without a Cleanup Procedure (희석에 의한 우유 중 $Aflatoxin\;M_1$의 효소면역측정법)

  • Shon, Dong-Hwa;Lim, Sun-Hee;Lee, Yin-Won
    • Korean Journal of Food Science and Technology
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    • v.28 no.6
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    • pp.1184-1187
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    • 1996
  • A simple and rapid detection system for $aflatoxin\;M_1\;(AFM_1)$ in cow's milk by an enzyme-linked immunosorbent assay (ELISA) was developed. Specific antibodies against $AFM_1$, conjugated to bovine serum albumin $(AFM_1-BSA)$ were raised in rabbits and purified. The cross-reactivities of the antibodies against aflatoxin analogs were less than 29.9%. When a competitive direct ELISA (cdELISA) for $AFM_1$, established by use of the antibodies was applied to the spike test of $AFM_1$ onto uncontaminated cow's milk, the assay recovery was unstable unless cow's milk was diluted to 40% (2:3) with phosphate buffered saline (PBS). In that condition of sample dilution, the mean ELISA recovery of $AFM_1$, from the cow's milk was 113% (coefficient of variation (CV) of each recovery percentage, 8.2%) in the range of $0.3{\sim}3.0\;ppb$. These results showed that the ELISA system could be a convenient tool to monitor the contamination of AFM1 more than 0.5 ppb in cow's milk (FDA allowance limit) easily.

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Apoptotic Activity of Curcumin and EF-24 in HTB-41 Human Salivary Gland Epidermoid Carcinoma Cells

  • Kim, Ji-Won;Lee, Seul Ah;Go, Dae-San;Park, Byung-Sun;Kim, Su-Gwan;Yu, Sun-Kyoung;Oh, Ji-Su;Kim, Chun Sung;Kim, Jeongsun;Park, Jong-Tae;Kim, Do Kyung
    • International Journal of Oral Biology
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    • v.40 no.2
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    • pp.63-69
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    • 2015
  • Curcumin (diferuloylmethane), a constituent of turmeric powder derived from the rhizome of Curcuma longa, has been shown to inhibit the growth of various types of cancer cells by regulating cell proliferation and apoptosis. However, a need exists to design more effective analogs because of curcumin's poor intestinal absorption. EF-24 (diphenyl difluoroketone), the monoketone analog of curcumin, has shown good efficacy in anticancer screens. However, the effects of curcumin and EF-24 on salivary gland epidermoid carcinoma cells are not clearly established. The main goal of this study was to investigate the effects of curcumin and EF-24 on cell growth and induction of apoptosis in human salivary gland epidermoid carcinoma cells. Our studies showed that curcumin and EF-24 inhibited the growth of HTB-41 cells in a dose- and time-dependent manner, and the potency of EF-24 was > 34-fold that of curcumin. Treatment with curcumin or EF-24 resulted in nuclear condensation and fragmentation in HTB-41 cells, whereas the control HTB-41 cell nuclei retained their normal regular and oval shape. Curcumin and EF-24 promoted proteolytic cleavages of procaspase-3/-7/-9, resulting in an increase in the amount of cleaved caspase-3/-7/-9 in the HTB-41 cells. Caspase-3 and -7 activities were detected in viable HTB-41 cells treated with curcumin or EF-24. These results suggest that the curcumin and EF-24 inhibit cell proliferation and induce apoptosis in HTB-41 human salivary gland epidermoid carcinoma cells, and that they may have potential properties as an anti-cancer drug therapy.

Comparison of Inodilator Effect of Higenamine, YS49, YS51, Tetrahydroisoquinoline Analogs, and Dobutamine in the Rat

  • Chong, Won-Seog;Lee, Young-Soo;Kang, Young-Jin;Lee, Duck-Hyung;Ryu, Jae-Chun;Yun-Choi, Hye-Sook;Chang, Ki-Churl
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.3
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    • pp.323-330
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    • 1998
  • Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethylamines. Many of them, especially with 6,7-disubstitution, demonstrate a relatively high affinity for catecholamines. Present study examines the pharmacological action of limited series of THI, using rats' isolated atria and aorta. In addition, a $[^3H]$ prazosin displacement binding study with THI compounds was performed, using rat brain homogenates to investigate whether these probes have ?${\alpha}$-adrenoceptor affinity. We also compared the vascular relaxation potency of these probes with dobutamine. YS 49, YS 51, higenamine and dobutamine, concentration-dependently, relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ${\mu}M$) in which $pEC_{50}$ were $5.56{\pm}0.32$ and $5.55{\pm}0.21$, $5.99{\pm}1.16$ and $5.57{\pm}0.34$, respectively. These probes except higenamine also relaxed KCl (65.4 mM)-contracted aorta. In isolated rat atria, all THIs and dobutamine increased heart rate and contractile force. In the presence of propranolol, the concentration response curves of YS 49 and YS 51 shifted to the right and resulted in $pA_2$ values of $8.07{\pm}0.84$ and $7.93{\pm}0.11$, respectively. The slope of each compound was not deviated from unity, indicating that these chemicals are highly competitive at the cardiac ?${\beta}-adrenoceptors$. YS 49, YS 51, and higenamine showed ?${\alpha)-adrenoceptor$ affinity in rat brain, in which the dissociation constant $(K_i)$ was 2.75, 2.81, and 1.02 ${\mu}M$, respectively. It is concluded, therefore, that THI alkaloids have weak affinity to ${\alpha)_1-adrenoceptor$ in rat aorta and brain, respectively, while these probes show relatively high affinity for cardiac ${\beta}-adrenoceptors$. Thus, these chemicals may be useful in the treatment of congestive heart failure.

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Screening of anti-obesity drugs, their analogues and prohibited ingredients in slimming foods (식품 중 부정 혼입된 비만치료제 및 사용금지 성분 실태조사)

  • Yun, Jisuk;Choi, Jangduck;Kwon, Kisung;Jo, Cheon-Ho
    • Korean Journal of Food Science and Technology
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    • v.48 no.5
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    • pp.424-429
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    • 2016
  • Globally, obesity has been recognized as a serious health problem. Recently, slimming foods for weight loss and maintenance were found to contain anti-obesity drugs, their analogues, and prohibited ingredients. To avoid inspections by the Government, structurally modified analogs have been continuously synthesized. For rapid determination of adulterated slimming products, we simultaneously analyzed 21 illegal compounds using liquid chromatography (LC) equipped with photo diode array, and LC coupled with tandem mass spectrometry. The validation of the method was performed with regard to selectivity, linearity, limit of detection, limit of quantification, precision, and accuracy. We purchased 128 samples from the Korean market and online sources in the year 2015. In 31 samples, 3 illegal compounds were detected as follows: 9.9-135.3 mg/g of sibutramine, 0.2-17.5 mg/g of yohimbine, and 1.8 mg/g of icariin. This simultaneous detection method might prove to be a simple and rapid analysis for monitoring illegal compounds in slimming foods.

Habitual Fallacy or Intentional Propaganda: Understanding the Mechanism of Re-constructing North Korean Myth (관습적 오류 혹은 의도적 프로파간다: 북한관련 '의혹'의 실체적 진실과 담론 왜곡의 구조)

  • Kim, Sunghae;Lu, Liu;Kim, Tongkyu
    • Korean Journal of Legislative Studies
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    • v.23 no.1
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    • pp.187-226
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    • 2017
  • North Korea discourse is doubtful. A considerable portion is distorted under political objectives, group identity, and interests. Surely, there are facts based on North Korea's conducts. Apparent deceptions commonly exist as well though. Korean media does not endeavor to set the records straight and there are no revision towards mislead information. This is substantially dangerous as it can misjudge North Korean policies, beget national antipathy, and interferes with rational and constructive policy making. This study stems from such concerns and takes such cases as HEU(Highly Enriched Uranium) suspicion of 2002, dispute covering BDA(Banco Delta Asia)'s counterfeiting, and the abandonment of the Geneva Agreed Framework into consideration. The first part concentrates on fathoming the truth of the three cases. References from US government, academia, think tanks, media were inquired with an addition of secondary material from Korea and China. Secondly it examines whether domestic news properly reflects the precedent facts along the process of discovery. The cause and solution suggested by domestic media were organized and inductively reconstituted to frames. The last study questions the structural factors that reproduces suspicion analogs. Today's dangers facing Korean society are essentially not natural but artificial. This research hopes to foster peace by analyzing related discourses that are infamous to reinterpret reality.

Short Bowel Syndrome as the Leading Cause of Intestinal Failure in Early Life: Some Insights into the Management

  • Goulet, Olivier;Nader, Elie Abi;Pigneur, Benedicte;Lambe, Cecile
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.22 no.4
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    • pp.303-329
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    • 2019
  • Intestinal failure (IF) is the critical reduction of the gut mass or its function below the minimum needed to absorb nutrients and fluids required for adequate growth in children. Severe IF requires parenteral nutrition (PN). Pediatric IF is most commonly due to congenital or neonatal intestinal diseases or malformations divided into 3 groups: 1) reduced intestinal length and consequently reduced absorptive surface, such as in short bowel syndrome (SBS) or extensive aganglionosis; 2) abnormal development of the intestinal mucosa such as congenital diseases of enterocyte development; 3) extensive motility dysfunction such as chronic intestinal pseudo-obstruction syndromes. The leading cause of IF in childhood is the SBS. In clinical practice the degree of IF may be indirectly measured by the level of PN required for normal or catch up growth. Other indicators such as serum citrulline have not proven to be highly reliable prognostic factors in children. The last decades have allowed the development of highly sophisticated nutrient solutions consisting of optimal combinations of macronutrients and micronutrients as well as guidelines, promoting PN as a safe and efficient feeding technique. However, IF that requires long-term PN may be associated with various complications including infections, growth failure, metabolic disorders, and bone disease. IF Associated Liver Disease may be a limiting factor. However, changes in the global management of IF pediatric patients, especially since the setup of intestinal rehabilitation centres did change the prognosis thus limiting "nutritional failure" which is considered as a major indication for intestinal transplantation (ITx) or combined liver-ITx.

A Study for Generation of Artificial Lunar Topography Image Dataset Using a Deep Learning Based Style Transfer Technique (딥러닝 기반 스타일 변환 기법을 활용한 인공 달 지형 영상 데이터 생성 방안에 관한 연구)

  • Na, Jong-Ho;Lee, Su-Deuk;Shin, Hyu-Soung
    • Tunnel and Underground Space
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    • v.32 no.2
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    • pp.131-143
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    • 2022
  • The lunar exploration autonomous vehicle operates based on the lunar topography information obtained from real-time image characterization. For highly accurate topography characterization, a large number of training images with various background conditions are required. Since the real lunar topography images are difficult to obtain, it should be helpful to be able to generate mimic lunar image data artificially on the basis of the planetary analogs site images and real lunar images available. In this study, we aim to artificially create lunar topography images by using the location information-based style transfer algorithm known as Wavelet Correct Transform (WCT2). We conducted comparative experiments using lunar analog site images and real lunar topography images taken during China's and America's lunar-exploring projects (i.e., Chang'e and Apollo) to assess the efficacy of our suggested approach. The results show that the proposed techniques can create realistic images, which preserve the topography information of the analog site image while still showing the same condition as an image taken on lunar surface. The proposed algorithm also outperforms a conventional algorithm, Deep Photo Style Transfer (DPST) in terms of temporal and visual aspects. For future work, we intend to use the generated styled image data in combination with real image data for training lunar topography objects to be applied for topographic detection and segmentation. It is expected that this approach can significantly improve the performance of detection and segmentation models on real lunar topography images.