• Title/Summary/Keyword: Side resistance

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Characteristics of Cancer Stem Cells and Immune Checkpoint Inhibition (암줄기세포의 특성 및 면역관문억제)

  • Choi, Sang-Hun;Kim, Hyunggee
    • Journal of Life Science
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    • v.29 no.4
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    • pp.499-508
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    • 2019
  • Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

Generation of a transgenic pig expressing human dipeptidylpeptidase-4 (DPP-4) (Human dipeptidylpeptidase-4(DPP-4) 발현 형질전환 돼지의 생산)

  • Chung, Hak Jae;Sa, Soo Jin;Baek, Sun Young;Cho, Eun Suek;Kim, Young Shin;Hong, Jun Ki;Cho, Kyu Ho;Kim, Ji Youn;Park, Mi Ryung;Kim, Kyung Woon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.20 no.9
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    • pp.306-314
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    • 2019
  • As dipeptidyl peptidase-4(DPP-4) inhibitors are used widely as a secondary treatment for type 2 diabetes because they tend to be well tolerated with minimal side effects, the human DPP-4(hDPP-4) gene was injected into a pig zygote through micro-injection, and 1-cell stage fertilized embryos were then transplanted surgically into the oviduct. Three pigs were fertilized with hDPP-4 genes and produced sixteen piglets, in which one male piglet was identified to be transgenic. Finally, transgenic pigs showing hDPP-4 gene expression in the tail were produced. Western blot and RT-PCR analysis confirmed that the hDPP-4 is expressed strongly in the membrane cells of the transgenic pig, and that the hDPP-4 gene appears in various tissues and tails. This suggests that the expression vector is normally expressed in transgenic pigs. These results are anticipated to be a model animal to check the endocrine function for insulin resistance that occurs in a hDPP-4 transgenic pig and to increase its value for use as a material in newly developed medicines.

α-Mangostin and Apigenin Induced Cell Cycle Arrest and Programmed Cell Death in SKOV-3 Ovarian Cancer Cells

  • Ittiudomrak, Teeranai;Puthong, Songchan;Roytrakul, Sittiruk;Chanchao, Chanpen
    • Toxicological Research
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    • v.35 no.2
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    • pp.167-179
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    • 2019
  • Ovarian cancer is the fifth main cause of pre-senescent death in women. Although chemotherapy is generally an efficient treatment, its side effects and the occurrence of chemotherapeutic resistance have prompted the need for alternative treatments. In this study, ${\alpha}$-mangostin and apigenin were evaluated as possible anticancer alternatives to the chemotherapeutic drug doxorubicin, used herein as a positive control. The ovarian adenocarcinoma cell line SKOV-3 (ATCC No. HTB77) was used as model ovarian cancer cells, whereas the skin fibroblast line CCD-986Sk (ATCC No. CRL-1947) and lung fibroblast line WI-38 (ATCC No. CCL-75) were used as model untransformed cells. Apigenin and doxorubicin inhibited the growth of SKOV-3 cells in a dose- and time-dependent manner. After 72 hr exposure, doxorubicin was mostly toxic to SKOV-3 cells, whereas apigenin was toxic to SKOV-3 cells but not CCD-986Sk and WI-38 cells. ${\alpha}$-Mangostin was more toxic to SKOV-3 cells than to CCD-986Sk cells. A lower cell density, cell shrinkage, and more unattached (floating round) cells were observed in all treated SKOV-3 cells, but the greatest effects were observed with ${\alpha}$-mangostin. With regard to programmed cell death, apigenin caused early apoptosis within 24 hr, whereas ${\alpha}$-mangostin and doxorubicin caused late apoptosis and necrosis after 72 hr of exposure. Caspase-3 activity was significantly increased in ${\alpha}$-mangostin-treated SKOV-3 cells after 12 hr of exposure, whereas only caspase-9 activity was significantly increased in apigenin-treated SKOV-3 cells at 24 hr. Both ${\alpha}$-mangostin and apigenin arrested the cell cycle at the $G_2/M$ phase, but after 24 and 48 hr, respectively. Significant upregulation of BCL2 (apoptosis-associated gene) and COX2 (inflammation-associated gene) transcripts was observed in apigenin- and ${\alpha}$-mangostin-treated SKOV-3 cells, respectively. ${\alpha}$-Mangostin and apigenin are therefore alternative options for SKOV-3 cell inhibition, with apigenin causing rapid early apoptosis related to the intrinsic apoptotic pathway, and ${\alpha}$-mangostin likely being involved with inflammation.

Immunostimulatory Activity of Agarwood through Activation of MAPK Signaling Pathway in RAW 264.7 Murine Macrophages (RAW 264.7 대식세포에서 MAPKs 신호 전달 경로의 활성화를 통한 침향의 면역 자극 활성)

  • Ji, Seon Yeong;Hwangbo, Hyun;Lee, Hyesook;Koo, Young Tae;Kim, Jin Soo;Lee, Ki Won;Noh, Dong Jin;Choi, Yung Hyun
    • Journal of Life Science
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    • v.31 no.8
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    • pp.745-754
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    • 2021
  • Deterioration of the immune function weakens the body's resistance to various infections, leading to a series of diseases. Immunomodulatory biomaterials have been used to reduce the side effects of immunosuppressants or to enhance immunity. Agarwood is the aromatic resinous portion of Aquilaria trees that has been traditionally used as a medicinal herb for the treatment of various diseases. Although previous studies have shown that agarwood can improve the body's immunity, evidence for this claim is still lacking. In this study, the immune-enhancing effects of the agarwood methanol extracts of Aquilaria malaccensis Lamk were evaluated in a RAW 264.7 macrophage model. Based on the results, the agarwood extracts markedly enhanced phagocytosis in the absence of cytotoxicity. The agarwood extract-treated RAW 264.7 cells exhibited the typical morphology of activated macrophages, which are spindle-shaped with elongated filopodia. Agarwood extract also significantly increased the production of nitric oxide (NO), which is associated with the increased expression of inducible NO synthase. Moreover, the secretion and expression levels of cytokines, such as tumor necrosis factor-α and interleukin (IL)-1β and IL-6, were increased by agarwood treatment. Notably, these are also associated with a mitogen-activated protein kinase signaling pathway. Taken together, our findings provide scientific evidence that agarwood has potential immune-enhancing effects in vitro.

Synthesis of SiO2/Ag Core-shell Nanoparticles for Conductive Paste Application (SiO2/Ag 코어-쉘 나노입자의 합성 및 전도성 페이스트 적용)

  • Sim, Sang-Bo;Han, Jong-Dae
    • Applied Chemistry for Engineering
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    • v.32 no.1
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    • pp.28-34
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    • 2021
  • SiO2/Ag core-shell nanoparticles were synthesized by combining modified Stöber process and reverse micelle method using acetoxime as a reducing agent in water/dodecylbenzenesulfonic acid (DDBA)/cyclohexane reverse micells. The SiO2/Ag core-shells were studied for structure, morphology and size using UV-visible spectroscopy, XRD, SEM and TEM. The size of a SiO2/Ag core-shell could be controlled by changing the [water]/[DDBA] molar ratio (WR) values. The size and the polydispersity of SiO2/Ag core-shells increased with increase of the WR value. The resultant Ag nanoparticles exhibit a strong surface plasmon resonance (SPR) peak at 430 nm over the amorphous SiO2 nanoparticles. The SPR peak shifted to the red side with increase in nanoparticle size. Conductive pastes with 70 wt% SiO2/Ag core-shell were prepared, and the pastes were coated on the PET films using a screen-printing method. The printed paste film of the SiO2/Ag core-shell showed higher surface resistance than the commercial Ag paste in the range of 460~750 µΩ/sq.

Evaluation of the Soil-Structure Interaction of a MDOF Column Type Structure on Group Piles Based on the Large Scale 1g Shaking Table Test and the Numerical Analysis (대형 진동대 실험 및 수치해석을 이용한 다자유도 기둥 구조물과 군말뚝 기초의 지반-구조물 상호작용 평가)

  • Chae, Jonghoon;Yoon, Hyungchul;Ahn, Jaehun;Jung, Jongwon
    • Journal of the Korean Geotechnical Society
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    • v.38 no.4
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    • pp.47-58
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    • 2022
  • Many 1g shaking table tests with an SDOF structure supported by a single pile were performed to evaluate the soil-structure interaction (SSI) effect. Since most structures supported by group piles are MDOF structures with columns, the SSI effect is simulated using a large 1g shaking table test and numerical analysis. According to the results, the movement in the piles tends to increase with input acceleration and when the input frequency is similar to the natural frequency. Furthermore, the slope of the dynamic p-y curve remains constant regardless of the variation of acceleration and input frequency. According to the results of the dynamic p-y backbone curve and the moment of group piles, a center pile with a leading pile has more soil resistance than side piles with a trailing pile, and the effect of group piles is observed above the 7D center to center pile distance.

Core-shell TiO2/Ag Nanoparticle Synthesis and Characterization for Conductive Paste (전도성 페이스트용 코어-쉘 TiO2/Ag 나노입자의 합성 및 특성 연구)

  • Sang-Bo, Sim;Jong-Dae, Han
    • Applied Chemistry for Engineering
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    • v.34 no.1
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    • pp.36-44
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    • 2023
  • Core-shell TiO2/Ag nanoparticles were synthesized by a modified sol-gel process and the reverse micelle method using acetoxime as a reducing agent in water/dodecylbenzenesulfonic acid (DDBA)/cyclohexane. The structure, shape, and size of the TiO2/Ag nanoparticles were investigated using X-ray diffraction (XRD), UV-visible spectroscopy, scanning electron microscope (SEM), transmission electron microscope (TEM), and thermogravimetric analysis (TGA). The size of TiO2/Ag nanoparticles could be controlled by changing the [water]/[DDBA] molar ratio values. The size and the polydispersity of TiO2/Ag nanoparticles increased when the [water]/[DDBA] molar ratio rose. The resultant Ag nanoparticles over the anatase crystal TiO2 nanoparticles exhibited a strong surface plasmon resonance (SPR) peak at about 430 nm. The SPR peak shifted to the red side with the increase in nanoparticle size. Conductive pastes with 70 wt% TiO2/Ag nanoparticles were prepared, and the pastes were coated on the PET films using a screen-printing method. The printed paste films of the TiO2/Ag nanoparticles demonstrated greater surface resistance than conventional Ag paste in the range of 405~630 μΩ/sq.

Analysis of Dynamics Mechanism to Regulation and Punishment of Fishing Boats using System Dynamics (시스템다이내믹스를 이용한 낚시어선의 단속과 처벌에 따른 동태적 매커니즘 분석)

  • Moon, JungHwan
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.28 no.2
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    • pp.270-279
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    • 2022
  • In this paper, system dynamics considering dynamics and time was examined to study the changes in system structure according to reinforcement (policy intervention) of regulation and punishment for fishing boats, and the strategizing directions were analyzed. Until now, regulations and punishments on fishing boats have been conducted temporarily and short-term as a precautionary measure to prevent accidents and imposed penalties. However, due to various anomalous side effects, the expected results were not achieved, negligent accidents occurred constantly, and follow-up measures were repeated. Resultantly, the regulation and punishment of fishing boats is a reinforced safety standard, and there is a necessity to improve facilities, equipment, and industry, and develop technology (including time delay) to prevent accidents. However, as the negative (illegal) activities continue without immediate and significant resistance, the safety blind spot for accident prevention cannot be minimized. Thus, policy intervention based on linear thinking without sufficiently considering variables of the dynamic mechanism and time can distort the basic values pursued by the policy. For the regulation and punishment of fishing boats, a strategy to supplement the mechanism should be prepared prior to the preparation of reinforced safety standards. Improvement and development of related technologies, mandatory training hours for anglers, fishing industry, and related organizations, proposal of specific action plan for Fishing Management and Promotion Act for growing fishing-related industries.

An Experimental Study on Relationship Between Half-Cell Potential and Corrosion Current Density of Chloride-Induced Corroded Steel in Concrete (염해에 따라 콘크리트 속에서 부식된 철근의 반전지전위와 부식전류밀도의 상관관계에 관한 실험적 연구)

  • Jo, Sang-Hyeon;Kim, Dong-Won;Kee, Seong-Hoon
    • Journal of the Korea institute for structural maintenance and inspection
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    • v.26 no.6
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    • pp.1-13
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    • 2022
  • This study aims to investigate the feasibility of the half-cell potential (HCP) measurements on the concrete surface for evaluation of corrosion rate (or corrosion levels) of reinforcing steel in concrete. A series of experimental study is performed to measure HCP (or corrosion potential, Ecorr) and corrosion current density (icorr) of reinforcing steel in concrete cube specimens, with a side length of 200 mm. Various corrosion levels in a range of 0% to 20% of the test specimens are accelerated by impressing current to the reinforcing steel in concrete immersed in 3.0 % NaCl solution. HCP is measured in accordance with ASTM C876-15, and corrosion current density is determined by using the Stern-Geary equation and measured polarization resistance measured by electrochemical impedance spectroscopy (EIS). As a result, a numerical formula that relates HCP and icorr in the test specimen is established by a regression analysis of the measured data in this study. It is observed that HCP is linearly correlated with log(icorr) with a R2 greater than 0.87, which is less affected by the experimental variables such as concrete mixture proportion, diameter of reinforcing steel and the amount of applied current in this study. These results exhibit that HCP measurements could be effective for evaluation of corrosion rate (or corrosion levels) of reinforcing steel in concrete in the case of exposed to a certain consistent environment.

Plant-derived Anti-HIV Natural Products: A Review of Recent Research (천연물의 항 HIV 효능에 대한 최신 연구동향)

  • Karadeniz, Fatih;Oh, Jung Hwan
    • Journal of Life Science
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    • v.32 no.9
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    • pp.734-741
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    • 2022
  • Currently, around 40 million people worldwide are living with human immunodeficiency virus (HIV) infection making HIV a critical global health risk. Present therapies for HIV infection consist of drug cocktails that target different steps of the HIV life cycle to prevent infection, replication, and release of the virus. Due to its mutating nature, drug resistance coupled with side-effects of long-term drug use, novel strategies, and pharmaceuticals to treat and manage HIV infection are constant needs and continuously being studied. Plants allocate a major repertoire of chemical diversity and are therefore regarded as an important source of new bioactive agents that can be utilized against HIV. Since the early 1990s, upon recommendations of the World Health Organization, numerous studies reported phytochemicals from different structural classes such as flavonoids, coumarins, tannins and terpenes with strong inhibitory effects against HIV infection. The present review gathered and presented recent research (2021-present) on plant extracts and phytochemicals that exhibit anti-HIV properties with the aim of providing insights into future studies where ethnomedical and underutilized plant sources may yield important natural products against HIV. Considering the relation and importance of HIV treatment with current viral infection risks such as SARS-CoV-2, screening plants for anti-HIV agents is an important step towards the discovery of novel antivirals.