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Unlocking the Therapeutic Potential of BCL-2 Associated Protein Family: Exploring BCL-2 Inhibitors in Cancer Therapy

  • Bisan El Dakkak;Jalal Taneera;Waseem El-Huneidi;Eman Abu-Gharbieh;Rifat Hamoudi;Mohammad H. Semreen;Nelson C. Soares;Eman Y. Abu-Rish;Mahmoud Y. Alkawareek;Alaaldin M. Alkilany;Yasser Bustanji
    • Biomolecules & Therapeutics
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    • v.32 no.3
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    • pp.267-280
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    • 2024
  • Apoptosis, programmed cell death pathway, is a vital physiological mechanism that ensures cellular homeostasis and overall cellular well-being. In the context of cancer, where evasion of apoptosis is a hallmark, the overexpression of anti-apoptotic proteins like Bcl2, Bcl-xL and Mcl-1 has been documented. Consequently, these proteins have emerged as promising targets for therapeutic interventions. The BCL-2 protein family is central to apoptosis and plays a significant importance in determining cellular fate serving as a critical determinant in this biological process. This review offers a comprehensive exploration of the BCL-2 protein family, emphasizing its dual nature. Specifically, certain members of this family promote cell survival (known as anti-apoptotic proteins), while others are involved in facilitating cell death (referred to as pro-apoptotic and BH3-only proteins). The potential of directly targeting these proteins is examined, particularly due to their involvement in conferring resistance to traditional cancer therapies. The effectiveness of such targeting strategies is also discussed, considering the tumor's propensity for anti-apoptotic pathways. Furthermore, the review highlights emerging research on combination therapies, where BCL-2 inhibitors are used synergistically with other treatments to enhance therapeutic outcomes. By understanding and manipulating the BCL-2 family and its associated pathways, we open doors to innovative and more effective cancer treatments, offering hope for resistant and aggressive cases.

Prostaglandin synthase activity of sigma- and mu-class glutathione transferases in a parasitic trematode, Clonorchis sinensis

  • Jiyoung Kim;Woon-Mok Sohn;Young-An Bae
    • Parasites, Hosts and Diseases
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    • v.62 no.2
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    • pp.205-216
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    • 2024
  • Sigma-class glutathione transferase (GST) proteins with dual GST and prostaglandin synthase (PGS) activities play a crucial role in the establishment of Clonorchis sinensis infection. Herein, we analyzed the structural and enzymatic properties of sigma-class GST (CsGST-σ) proteins to obtain insight into their antioxidant and immunomodulatory functions in comparison with mu-class GST (CsGST-µ) proteins. CsGST-σ proteins conserved characteristic structures, which had been described in mammalian hematopoietic prostaglandin D2 synthases. Recombinant forms of these CsGST-σ and CsGST-µ proteins expressed in Escherichia coli exhibited considerable degrees of GST and PGS activities with substantially different specific activities. All recombinant proteins displayed higher affinities toward prostaglandin H2 (PGS substrate; average Km of 30.7 and 3.0 ㎛ for prostaglandin D2 [PGDS] and E2 synthase [PGES], respectively) than those toward CDNB (GST substrate; average Km of 1,205.1 ㎛). Furthermore, the catalytic efficiency (Kcat/Km) of the PGDS/PGES activity was higher than that of GST activity (average Kcat/Km of 3.1, 0.7, and 7.0×10-3 s-1-1 for PGDS, PGES, and GST, respectively). Our data strongly suggest that the C. sinensis sigma- and mu-class GST proteins are deeply involved in regulating host immune responses by generating PGD2 and PGE2 in addition to their roles in general detoxification.

Influence of aluminum and vanadium oxides on copper borate glass: A physical/radiological study

  • Islam M. Nabil;Moamen G. El-Samrah;Mahmoud Y. Zorainy;H.Y. Zahran;Ahmed T. Mosleh;Ibrahim S. Yahia
    • Nuclear Engineering and Technology
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    • v.56 no.8
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    • pp.3335-3346
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    • 2024
  • Due to the radiation released by commonly used isotopes, many nuclear, medical, and industrial facilities require proper radiation shielding. In this work, distinct copper borate glasses intercalated with varied aluminum and vanadium oxide (Al2O3 and V2O5) content have been synthesized and used against radiation (gamma rays and fast/thermal neutrons). The different percents were as follows: [60% B2O3 + 35% CuO + (5-x)% Al2O3 + xV2O5], where x = 0, 1, and 2.5 wt.%, which was coded as BCu(5-x)Al:xV. The synthesized glass samples were characterized using Fourier transforms, infrared, and X-Raydiffraction analysis. Experimentally, the radiation shielding possessions of the samples were established using an HPGe detector at the gamma energy lines 0.356 MeV, 0.661 MeV, 1.173 MeV, and 1.332 MeV. Also, the prepared glasses were investigated theoretically using the Monte Carlo code (MCNP5) at photon energies of 0.015-15 MeV. Also, the fast and thermal neutron macroscopic effective removal cross-sections were calculated using MRCsC and JANIS-4.1 software, respectively. The prepared sample BCu2.5Al:2.5V, which has a vanadium and aluminum content of 2.5%, has the highest linear attenuation coefficient as well as the highest removal cross-section for fast, and thermal neutrons.

Comprehensive analysis of lncRNAs modified by m6A methylation in sheep skin

  • Jinzhu Meng;Jianping Li;Yuanyuan Zhao
    • Animal Bioscience
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    • v.37 no.11
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    • pp.1887-1900
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    • 2024
  • Objective: N6-methyladenosine (m6A) is the most prevalent methylation of mRNA and plays crucial roles in various physiological processes, including pigmentation. Yet, the regulatory mechanisms, including long noncoding RNAs (lncRNAs) m6A methylation contributing to pigmentation in sheep skin remains unclear. The purpose of this study was to identify potential lncRNAs and the m6A methylation of lncRNAs associated with pigmentation. Methods: RNA-seq and MeRIP-seq were performed to study the expression of lncRNAs and the m6A methylation of lncRNAs in black and white sheep skin. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency with the RNA-seq and MeRIP-seq data. Results: We identified 168 differentially expressed lncRNAs between the two sheep skin colors. The differentially expressed lncRNAs enriched in the pathway of ECM-receptor interaction, Rap1 signaling pathway, and Non-homologous end-joining may play essential roles in pigmentation. We identified 577 m6A peaks and 617 m6A peaks in black and white sheep skin, respectively, among which 20 m6A peaks showed significant differences. The enriched motif in sheep skin was "GGACU", which aligned with the consensus motif "RRACH" (R = A or G, H = A, C or U). Differently methylated lncRNAs enriched in PI3K-Akt signaling pathway and Wnt signaling pathway might participate in skin pigmentation. ENSOARG00020015168 was the unique lncRNA with high expression and methylation (Hyper-Up) in black sheep shin. A lncRNA-mRNA network was constructed, with pigmentation-related genes, such as PSEN2, CCND3, COL2A1, and ERCC3. Conclusion: The m6A modifications of lncRNAs in black and white colored sheep skin were analyzed comprehensively, providing new candidates for the regulation of pigmentation.

Control of Chlorinated Volatile Pollutants at Indoor Air Levels Using Polymer-based Photocatalyst, Composite

  • Kim, Byeong-Chan;Kim, Hye-Jin;Kim, Ji-Eun;Park, Eun-Ju;Noh, Ji-Sun;Kang, Hyun-Jung;Shin, Seung-Ho;Jo, Wan-Kuen
    • Clean Technology
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    • v.19 no.2
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    • pp.105-112
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    • 2013
  • In this study, polyaniline (PANI)-based $TiO_2$ (PANI-$TiO_2$) composites calcined at different temperatures were prepared and their applications for control of trichloroethylene (TCE) and tetrachloroethylene (TTCE) at indoor air levels were investigated. For these target compounds, the photocatalytic control efficiencies of PANI-$TiO_2$ composites did not exhibit any trend with varying calcination temperatures (CTs). Rather, the average control efficiencies of PANI-$TiO_2$ composites over 3-h photocatalytic process increased from 61 to 72% and from 21 to 39% for TCE and TTCE, respectively, as the CT increased from 350 to $450^{\circ}C$. However, for both the target compounds, the average control efficiencies of PANI-$TiO_2$ composites decreased gradually as the CT increased further to 550 and $650^{\circ}C$. These results were ascribed to contents of anatase crystal phase and specific surface area of different particle sizes in the PANI-$TiO_2$ composites, which were demonstrated by the X-ray diffraction and scanning electron microscopy images, respectively. At the lowest input concentration (IC, 0.1 ppm), average control efficiencies of TCE and TTCE were 72 and 39%, respectively, whereas at the highest IC (1.0 ppm) they were 52 and 18%, respectively. As stream flow rate increased from 0.1 to 1.0 L $min^{-1}$, the average control efficiencies of TCE and TTCE decreased from ca. 100 to 47% and ca. 100 to 18%, respectively. In addition, the average control efficiencies of TCE and TTCE decreased from ca. 100 to 23% and ca. 100 to 8%, respectively as the relative humidity increased from 20 to 95%. Overall, these findings indicated that as-prepared PANI-$TiO_2$ composites could be used efficiently for control of chlorinated compounds at indoor air levels;if operational conditions were optimized.

Reaction Mechanism and Curing Characteristics of Chicken Feather-Based Adhesives and Adhesive Properties of Medium-Density Fiberboard Bonded with the Adhesive Resins (닭털로 제조한 접착제의 반응기작 및 경화 특성과 이를 이용하여 제조한 중밀도섬유판의 접착 특성)

  • Yang, In;Park, Dae-Hak;Choi, Won-Sil;Oh, Sei Chang;Ahn, Dong-uk;Han, Gyu-Seong
    • Korean Chemical Engineering Research
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    • v.55 no.3
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    • pp.385-394
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    • 2017
  • In this study, reaction mechanism and curing characteristics of adhesives formulated with NaOH- and $H_2SO_4$-hydrolyzed chicken feather (CF) and formaldehyde-based crosslinkers were investigated by FT-IR and DSC. In addition, adhesive properties and formaldehyde emission of medium-density fiberboards (MDF) applied with the adhesives were measured. CF-based adhesives having a solid content of 40% and over were very viscous at $25^{\circ}C$, but the viscosity reduced to $300{\sim}660m{\cdot}Pa{\cdot}s$ at $50^{\circ}C$. Consequently, the adhesives could be used as a sprayable resin. Through the FT-IR spectra of liquid and cured CF-based adhesives, addition reaction of methylol group and condensation reaction between the functional groups with the use of formaldehyde-based crosslinkers were identified. From the analysis of DSC, it was elucidated for CF-based adhesives to require a higher pressing temperature or longer pressing time comparing to commercial urea-formaldehyde (C-UF) resin. MDF bonded with CF-based adhesives, which was formulated with 5% NaOH-hydrolyzed CF (CF-AK-5%) and PF of formaldehyde to phenol mole ratio of 2.5 (PF-2.5), and pressed for 8 min had higher MOR and IB than those with other CF-based adhesives. MOR and IB of MDF bonded with the CF-based adhesives regardless of formulation type and pressing time were higher than those with C-UF resin. When the values compared with the minimum requirements of KS standard, IB exceeded the KS standard in all formulations and pressing time, but MOR of only MDF bonded with CF-AK-5% and PF-2.5 and pressed for 8 min satisfied the KS standard. What was worse, 24-TS of MDF bonded with all CF-based adhesives did not satisfied the KS standard. However, MOR and 24-TS can be improved by increasing the target density of MDF or the amount of wax emulsion, which is added to improve the water resistance of MDF. Importantly, the use of CF-based adhesives decreased greatly the formaldehyde emission. Based on the results, we reached the conclusion that CF-based adhesives formulated under proper conditions had a potential as a sprayable resin for the production of wood panels.

Anti-oxidative Activities of Commercial Edible Plant Extracts Distributed in Korea (국내 유통 중인 식용식물 추출물의 항산화효과)

  • Kim, Kyung-Bum;Yoo, Ki-Hwan;Park, Ha-Yan;Jeong, Jong-Moon
    • Applied Biological Chemistry
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    • v.49 no.4
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    • pp.328-333
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    • 2006
  • Many plant extracts are known to have antioxidative effects. However, their activities can be reduced or disappeared during mass production process. The purpose of this study is to compare antioxidative effects of edible plant extracts distributed in Korea. forty three kinds of edible plant extracts commercially available in Korea were selected and investigated for their total phenolics contents and antioxidative potentials(DPPH radical and superoxide anion radical scavenging activities). In contents of total phenolics, the commercial plant extracts from Artemisia annua(whole plant), Ilex paraguariensis(leaf, Silybum marianum(fruit and leaf, Ulmus pumila(bark), Coliolus versicolor(fruit), and Curcuma longa(root and stem) contained over 70 mg/g of powder, DPPH radical scavenging activities($SC_{50}$, 50% scavenging concentration) of A. annua, I. paraguariensis, Pinus densiflora(leaf),S. marianum, U. pumila, and C. longa were $53.96{\pm}0.81\;ppm,\;24.61{\pm}2.12\;ppm,\;35.96{\pm}1.11\;ppm,\;57.46{\pm}2.13\;ppm,\;55.25{\pm}1.65\;ppm\;and\;12.99{\pm}1.67ppm$, respectively, while that of positive control(vitamin C) was $3.86{\pm}0.81\;ppm$. $SC_{50}$ values against superoxide anion radical of A. annua, Cinnamomum zeylanicum(bark), I. paraguariensis, Rubus coreanus(fruit and leaf), Morus alba(leaf), P. densiflora, S. marianum, U. pumila, C. versicolor, C. longa, Perilla frutescens var. acuta(leaf), and H. sabdariffa(leaf and newer) were $53.21{\pm}1.83ppm,\;50.12{\pm}2.12ppm,\;5.59{\pm}0.84ppm,\;41.60{\pm}8.93ppm,\;20.19{\pm}0.97ppm,\;15.19{\pm}1.66ppm,\;21.20{\pm}1.88ppm,\;15.71{\pm}0.91ppm,\;55.48{\pm}2.42ppm,\;52.12{\pm}2.44ppm,\;23.80{\pm}1.98ppm\;and\;11.14{\pm}0.51ppm$, respectively($SC_{50}$ value of vitamin C: $9.61{\pm}0.93ppm$). In particular, both 1 paraguariensis and P. densiflora had high content of phenolics as well as high scavenging activities of DPPH radical and superoxide anion radical. Consequently, above two commercial extracts may be useful as a source of antioxidative nutraceutics.

Studies on the Simplified Hemagglutination Reaction to Pasteurella multocida and the Stabilization of Erythrocytes (Pasteurella multocida에 대(對)한 간이적혈구(簡易赤血球) 응집반응(凝集反應)과 적혈구(赤血球)의 안정화(安定化)에 관(關)한 연구(硏究))

  • Lee, Hak Cheul;Chung, Yung Gun;Kim, Kyo-Joon
    • Korean Journal of Veterinary Research
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    • v.10 no.1
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    • pp.11-23
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    • 1970
  • Recently Carter(1952) reported the capsule antigens of Pasteurella multocida could be divided into four serological types A,B,C and D by means of precipitation tests. Subsequently he showed that the most sensitive for identification of these types involved the use of capsule substance adsorbed by erythrocytes in hemagglutination test. It may be somewhat difficult to conduct the hemagglutination test in small laboratory, because relatively large amounts of antisera and erythrocytes of the human O type are required for the test. A simple method for serological typing of P. multocida was the slide agglutination test employed by Little et al. (1943) and Namioka et al. (1962), but this method is still in controversy. The author tried adapting Carter's hemagglutination method to the slide method so called "micromethod technique", and studied on the stabilization of erythrocytes for use of slide hemagglutination to P. multocida although many invesigators reported the stabilization of erythrocytes. The results obtained are summarized as follows: 1. A simplified method (slide method) for capsule typing of the organism was developed by adapting Carter's hemagglutination reaction(tube method). Antibody-containing serum can be diluted serially on Boerner's microtest slide with capillary or serological pipetts with a considerable accuracy. The slide reaction can be carried out with case on the slide by adding $0.05m{\ell}$ of antigen-sensitized erythrocytes suspension diluted to one percent on $0.05m{\ell}$ of serially diluted antibody-containing sera, and the final result can be read after 60 minutes at the room temperature ($15^{\circ}C$). 2. It is difficult to determine superiority of inferiority between the slide method and the tube method on the pattern of the reaction of hemagglutination. 3. The pH range of 6.6 to 8.3 is optimal for the slide hemagglutination reaction. 4. The antigen-sensitization against erythrocytes at $37^{\circ}C$ is optimal for the slide hemagglutination. 5. Both the doses and concentration of antigen do not influence the antigen-adsorbing capacity of erythrocytes. 6. The reduction of antigen-sensitizing hours does not influence the antigen-adsorbing capacity of erythrocytes even 30 minutes. 7. The tannic acid treatment against formalinized and non-formalinized erythrocytes showed no effect on the reaction of hemagglutination. 8. The erythrocytes preserved at $4^{\circ}C$ in the ACD solution do not decrease the reactivity on the reaction of hemagglutination for 60 days, while they begin slight hemolysis 30 days after preserving. 9. The stable preparation of erythrocytes can be obtained by treating the cells at $37^{\circ}C$ for 20 hours with from 4 to 8 percent of formalin in saline or buffer. These cells can be preserved at $4^{\circ}C$ for more than 8 months experimented without hemolysis. With low concentration of formalin, the cells were not sufficiently stabilized resulting in the hemolysis after short period of preservation at $4^{\circ}C$. 10. The erythrocytes treated with 16 percent of formalin remain constantly or increase the reactivity for the reaction of hemagglutination. On the contrary, the cells treated with I to 8 percent of formalin decrease the reactivity. 11. There is no difference between nontreated fresh erythrocytes and the erythrocytes preserved in the ACD solution on the reactivity against the hemagglutination, and the erythrocytes treated with 16 percent of formalin showed the reactivity of higher level than that of the above two kinds of erythrocytes. 12. There is no difference between the saline and the isotonic buffer solution on the reaction of hemagglutination.

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Studies on the Morphological, Physical and Chemical Properties of the Korean Forest soil in Relation to the Growth of Korean White Pine and Japanese Larch (한국산림토양의 형태학적 및 이화학적성질과 낙엽송, 잣나무의 성장(成長)에 관한 연구(硏究))

  • Chung, In-Koo
    • Korean Journal of Soil Science and Fertilizer
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    • v.12 no.4
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    • pp.189-213
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    • 1980
  • 1. Aiming at supply of basic informations on tree species siting and forest fertilization by understanding of soil properties that are demanded by each tree species through studies of forest soil's morphological, physical and chemical properties in relation to tree growth in our country, the necessary data have been collected in the last 10 years, are quantified according to quantification theory and are analyzed in accordance with multi-variate analysis. 2. Test species, larch and the Korean white pine, are plantable in extensive areas from mid to north in the temperate zone and are the two most recommended reforestation tree species in Korea. However, their respective site demands are not known and they have been in confusion or considered demanding the same site during reforestation. When the Korean white pine is planted in larch sites, it has shown relatively good growth. But, when larch is planted in the Korean white pine site it can be hardly said that the larch growth is good. To understand on such a difference soil factors have been studied so as to see how the soil's morphological, physical and chemical factors affect tree growth helped with the electronic computer. 3. All the stands examined are man-made mature forests. From 294 larch plots and 259 white pine plots dominant trees are cut as samples and through stem analysis site index is determined. For each site index soil profiles are made in the related forest-land for analysis. Soil samples are taken from each profile horizon and forest-land productivity classification tables are worked out through physical and chemical analysis of the soil samples for each tree species for the study of relationships between physical, chemical and the combined physical/chemical properties of soil and tree growth. 4. In the study of relationships between physical properties of soil and tree growth it is found out that larch growth is influenced by the following factors in the order of deposit form, soil depth, soil moisture, altitude, relief, soil type, depth of A-horizon, soil consistency content of organic matter soil texture bed rock gravel content aspect and slope. For the Korean white pine the influencing factors' order is soil type, soil consistency bed rock aspect depth of A-horizon soil moisture altitude relief deposit form soil depth soil texture gravel content and slope. 5. In the study of relationships between chemical properties of soil and tree growth it is found out that larch growth is influenced by the following factors in the order of base saturation organic matter CaO C/N ratio, effective $P_2O_5$ PH.exchangeable $K_2O$ T-N MgO C E C Total Base and Na. For the Korean white pine the influencing factors' order is effective $P_2O_5$ Total Base T-N Na C/N ratio PH CaO base saturation organic matter exchangeable $K_2O$ C E C and MgO. 6. In the study of relationships between the combined physical and chemical properties of soil and tree growth it is found out that larch growth is influenced by the following factors in the order of soil depth deposit form soil moisture PH relief soil type altitude T-N soil consistency effective $P_2O_5$ soil texture depth of A-horizon Total Base exchangeable $K_2O$ and base saturation. For the Korean white pine the influencing factors' order is soil type soil consistency aspect effective $P_2O_5$ depth of A-horizon exchangeable $K_2O$ soil moisture Total Base altitude soil depth base saturation relief T-N C/N ratio and deposit from. 7. In the multiple regression of forest soil's physical properties larch's correlation coefficient is 0.9272 and for the Korean white pine it is 0.8996. With chemical properties larch has 0.7474 and the Korean white pine has 0.7365. So, the soil's physical properties are found out more closely related with tree growth than chemical properties. However, this seems due to inadequate expression of soil's chemical factors and it is proved that the chemical properties are not less important than the physical properties. In the multiple regression of the combined physical and chemical properties consisting of important morphological and physical factors as well as chemical factors of forest soils larch's multiple correlation coefficient is found out to be 0.9434 and for the Korean white pine it is 0.9103 leading to the highest correlation. 8. As shown in the partial correlation coefficients larch needs deeper soil depth than the Korean white pine and in the deposit form colluvial and creeping soils are demanded by the larch. Adequately moist to too moist should be soil moisture and PH should be from 5.5 to 6.1 for the larch. Demands of T-N soil texture and soil nutrients are higher for the larch than the Korean white pine. Thus, soil depth, deposit form, relief soil moisture PH N altitude and soil texture are good indicators for species sitings with larch and the Korean white pine while soil type and soil consistency are indicative only limitedly of species sitings due to their wide variation as plantation environments. For larch siting soil depth deposit form relief soil moisture PH soil type N and soil texture are indicators of good growth and for Korean white pine they are soil type soil consistency effective $P_2O_5$ and exchangeable $K_2O$, which is demanded more by the Korean white pine than larch generally. 9. Physical properties of soil has been known as affecting tree growth to greatest extent so far. However, as a result of this study it is proved through computer analysis that chemical properties of soil are not less important factors for tree growth than chemical properties and site demands for larch and the Korean white pine that have been uncertain So far could be clarified.

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Effect of Ginseng Saponins on the Biosynthesis of Prostaglandins (인삼 사포닌 성분이 프로스타글란딘류 생성에 미치는 영향)

  • 이선희;박찬웅
    • Journal of Ginseng Research
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    • v.13 no.2
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    • pp.202-210
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    • 1989
  • The effects of Ginseng saponins on the in vitro biosynthesis of prostaglandins were examined in order to identify the role of some Ginseng components on the regulation of arachidonic arid metabolism. The productions of prostaglandin $E_2$ (PG$E_2$), $F_2$ (PGF2), thromboxane $B_2$(TX$B_2$) and 6-ketoprostaglandin Fl (6-Keto-PGF1) from [3Hl-arachidonic acid were evaluatpf by radiochromatographic analysis with rabbit kidney microtome, human platelet homogenate and bovine aortic microsome. The amounts of the total prostaglandins produced by cyclooxygenase activity and malondialdehyde from arachidonic acid didn't show significant changes in the presence of Ginseng saponins. Both of panaxadiol and panaxatriol didn't affect the production of PG$E_2$ while the formations of PG$F_2$( and TX$B_2$( were nearkedly reduced and the production of prostacyclin was increased. The formation of TXBE was reduced by ginsenoside $Rb_2$, Rc, and Re, however the production of 6-Keto-PGF1 was increased dose dependently up to 1 mg/ml. Moreover, platelet aggregations induced by arachidonic acid and U46619 (9.11-methanepoxy PG$H_2$), TX$A_2$ mimetics, were also inhibited by three ginsenosides. The effect of G-Re on prostacyclin synthetase was inhibited by tranylcypromine, prostacyclin synthetase inhibitor. These results suggest that Ginseng saponins may not directly act on cyclooxygenase but affect on the divergent pathway from endoperoxide.

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