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The Functional Role of Lysosomes as Drug Resistance in Cancer (항암제 내성에 대한 라이소좀의 역할)

  • Woo, Seon Min;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.31 no.5
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    • pp.527-535
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    • 2021
  • Lysosomes are organelles surrounded by membranes that contain acid hydrolases; they degrade proteins, macromolecules, and lipids. According to nutrient conditions, lysosomes act as signaling hubs that regulate intracellular signaling pathways and are involved in the homeostasis of cells. Therefore, the lysosomal dysfunction occurs in various diseases, such as lysosomal storage disease, neurodegenerative diseases, and cancers. Multiple forms of stress can increase lysosomal membrane permeabilization (LMP), resulting in the induction of lysosome-mediated cell death through the release of lysosomal enzymes, including cathepsin, into the cytosol. Here we review the molecular mechanisms of LMP-mediated cell death and the enhancement of sensitivity to anticancer drugs. Induction of partial LMP increases apoptosis by releasing some cathepsins, whereas massive LMP and rupture induce non-apoptotic cell death through release of many cathepsins and generation of ROS and iron. Cancer cells have many drug-accumulating lysosomes that are more resistant to lysosome-sequestered drugs, suggesting a model of drug-induced lysosome-mediated chemoresistance. Lysosomal sequestration of hydrophobic weak base anticancer drugs can have a significant impact on their subcellular distribution. Lysosome membrane damage by LMP can overcome resistance to anticancer drugs by freeing captured hydrophobic weak base drugs from lysosomes. Therefore, LMP inducers or lysosomotropic agents can regulate lysosomal integrity and are novel strategies for cancer therapy.

Preparation and Characterization of Reduced Graphene Oxide with Carboxyl Groups-Gold Nanorod Nanocomposite with Improved Photothermal Effect (향상된 광열 효과를 갖는 카르복실화된 환원 그래핀옥사이드-골드나노막대 나노복합체의 제조 및 특성 분석)

  • Lee, Seunghwa;Kim, So Yeon
    • Applied Chemistry for Engineering
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    • v.32 no.3
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    • pp.312-319
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    • 2021
  • Photothermal therapy is a treatment that necrotizes selectively the abnormal cells, in particular cancer cells, which are more vulnerable to heat than normal cells, using the heat generated when irradiating light. In this study, we synthesized a reduced graphene oxide with carboxyl groups (CRGO)-gold nanorod (AuNR) nanocomposite for photothermal treatment. Graphene oxide (GO) was selectively reduced and exfoliated at high temperature to synthesize CRGO, and the length of AuNR was adjusted according to the amount of AgNO3, to synthesize AuNR with a strong absorption peak at 880 nm, as an ideal photothermal agent. It was determined through FT-IR, thermogravimetric and fluorescence analyses that more carboxyl groups were conjugated with CRGO over RGO. In addition, CRGO exhibited excellent stability in aqueous solutions compared to RGO due to the presence of carboxylic acid. The CRGO-AuNR nanocomposites fabricated by electrostatic interaction have an average size of ~317 nm with a narrow size distribution. It was confirmed that under radiation with a near-infrared 880 nm laser which has an excellent tissue transmittance, the photothermal effect of CRGO-AuNR nanocomposites was greater than that of AuNR due to the synergistic effect of the two photothermal agents, CRGO and AuNR. Furthermore, the results of cancer cell toxicity by photothermal effect revealed that CRGO-AuNR nanocomposites showed superb cytotoxic properties. Therefore, the CRGO-AuNR nanocomposites are expected to be applied to the field of anticancer photothermal therapy based on their stable dispersibility and improved photothermal effect.

Effect of Addition of β-TCP on Bioactivity and Mechanical Properties of Biodegradable PLA/β-TCP Composites (β-TCP 첨가량에 따른 생분해성 PLA/β-TCP 복합체의 생체활성과 기계적 특성 평가)

  • Moon, Hee-Jung;Kim, Seol-Ak;Kim, Dong-Ae
    • The Journal of the Korea Contents Association
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    • v.21 no.3
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    • pp.609-615
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    • 2021
  • The aim of the present study was to investigate the mechanical properties of melt-injected poly lactic acid (PLA) composites with β-tricalcium phosphate (β-TCP). The PLA mixed with calcined PLA/β-TCP powder to be contents of 0, 10, 30, 50 wt%, respectively, was dissolved in chloroform solvent under stirring for 24 h. Then the liquid mixtures were dropped into ethanol to extract solvent. After drying, the well-dispersed PLA/β-TCP composites were granulated and melt-injected to prepare specimens for various mechanical testing. PLA/β-TCP induced the precipitation of an apatite bone-mineral phase on the surface after immersion in a human simulated body fluid (SBF) for 90 days, showing in bioactivity. Mean various mechanical properties PLA/β-TCP composite were increased up to 10-30 wt% with significantly in part and composite were decreased 50 wt% of showing in mechanical properties. In conclusion, Over 30 wt% addition of β-TCP to PLA may be not advisable to improve the mechanical properties of melt-injected polymeric composites. Results indicated that β-TCP can be used considered as potential reinforcing agent for increasing mechanical properties for PLA. Therefore, it was suggest that the additional effects of β-TCP and research on a wide range of substances.

Protective Effect of Curcumin on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Obese Mice (비만마우스에서 Dextran Sulfate Sodium 유도 궤양성 대장염에 대한 커큐민의 보호효과)

  • Park, Ho
    • Korean Journal of Clinical Laboratory Science
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    • v.54 no.1
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    • pp.9-14
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    • 2022
  • Ulcerative colitis is a disease that causes inflammation in the mucosal or submucosal layer of the colon. Previous studies have reported that obesity increases the prevalence of ulcerative colitis and aggravates the progression. This study was therefore undertaken to investigate whether curcumin inhibits the progression of ulcerative colitis caused by obesity. Mice were bred on a high-fat diet to induce obesity, and curcumin was administered with the high-fat diet to confirm the anti-inflammatory effect. To induce ulcerative colitis, dextran sulfate sodium (DSS) was administered orally, and clinical symptoms of colitis were subsequently observed. For histological evaluation of curcumin, the colon, liver and abdominal fat tissue samples were prepared and analyzed by hematoxylin and eosin (H&E) and Alcian blue-periodic acid-Schiff (PAS) staining. Our results confirm that consumption of curcumin resulted in decreasing the score of the disease activity index, and inhibited shortening of the colon length. In addition, inflammatory cell infiltration and mucosal damage were inhibited in the colon tissue of ulcerative colitis exacerbated by obesity. We further confirmed that exposure to curcumin significantly reduced the steatosis area of the liver and adipocytes of abdominal fat. In conclusion, we believe that curcumin can be applied as a therapeutic agent to treat ulcerative colitis, by inhibiting the progression of colitis caused by obesity.

Isolation and molecular characterizations of canine distemper virus from a naturally infected Korean dog using Vero cells expressing dog signaling lymphocyte activation molecule

  • Yang, Dong-Kun;Kim, Ha-Hyun;Lee, Siu;Yoon, Yoon-Seek;Park, Jungwon;Oh, Dongryul;Yoo, Jae Young;Ji, Miryeon;Han, Bokhee;Oh, Subin;Hyun, Bang-Hun
    • Journal of Veterinary Science
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    • v.21 no.5
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    • pp.64.1-64.14
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    • 2020
  • Background: Canine distemper virus (CDV) infection results in high morbidity and mortality in dogs. There has been no report about Isolation of Korean CDV since 1980 in Korea. Objectives: To investigate the biological properties and the genetic characterization of Korean CDV. Methods: Vero cells expressing dog signaling lymphocyte activation molecule (dSLAM) gene named as Vero/dSLAM were used to isolate CDV using 17 samples. Diagnostic methods such as cytopathic effects, immunofluorescence assay, peroxidase linked assay, electron microscopy, rapid immunodiagnostic assay, and reverse transcription polymerase chain reaction were used to confirm the Korean CDV isolate as a CDV. The genetic analysis was performed through cloning and sequencing of hemagglutinin gene of CDV isolate. Results: A virus propagated in Vero/dSLAM cell was confirmed as CDV (CD1901 strain) based on the above methods. The CD1901 strain showed the highest viral titer (105.5 50% tissue culture infectious dose [TCID50]/mL) in the Vero/dSLAM cells at 4 days post inoculation, but did not form a fork on chorioallantoic membrane of 7-day-old egg. Ribavirin, a nucleotide analogue anti-viral agent, inhibits moderately the Korean CDV propagation in the Vero/dSLAM cells. The nucleotide and amino acid sequences of the H gene of CD1901 strain were compared with those of other CDV strains. The CD1901 strain belonged to Asia 1 group and had the highest similarity (99.9%) with the BA134 strain, which was isolated in China in 2008. Conclusions: We constructed successfully Vero/dSLAM and isolated one Korean CDV isolate (CD1901 strain) from a naturally infected dog. The CD1901 strain belonged to Asia 1 genotype.

Skin Moisturizing Activity of Unripe Apple(Immature Fruit of Malus pumila) in Mice (풋사과 추출물의 피부 보습 효과)

  • Park, Hye Rim;Kim, Jae Kwang;Lee, Jae Kyoung;Choi, Beom Rak;Kim, Jong Dae;Ku, Sae Kwang;Jegal, Kyung Hwan
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.35 no.4
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    • pp.63-74
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    • 2022
  • Objectives : Skin aging is generally characterized by wrinkles, sagging, loss of elasticity roughness, pigmentation and dryness. This changes is caused by reducing the elements constituting the extracellular matrix contributing to the physiological properties of the skin, such as collagen fiber, elastic fiber, and hyaluronic acid. Adequate skin hydration is important to maintain normal skin function and reduce skin aging. The present study is objective to observe skin moisturizing effects of Unripe apple(UA, Immature fruit of Malus pumila Mill) in vivo and its underlying molecular mechanisms. Methods : ICR mice were orally administerd UA(100, 200 and 400mg/kg/day) for 8 weeks, and skin water contents and the expression of transforming growth factor (TGF)-𝛽1, ceramide, hyaluronan and collagen type I(COL1) were measured in dorsal back skin of the mice. Gene expression of hyaluronan synthase(HAS1, HAS2, HAS3), collagen synthase(COL1A1, COL1A2) and TGF-𝛽1 were also determined by realtime RT-PCR. Results : Skin water contents and the expression of TGF-𝛽1, ceramide, COL1 and hyaluronan were significantly increased in UA group(100, 200 and 400mg/kg/day) compared to vehicle control. The mRNA expression of HAS isoform(HAS1, HAS2, HAS3), COL1A1, COL1A2, and TGF-𝛽1 were also significantly increased by UA. Conclusions : UA has skin moisturizing effects and enhancement activities in skin function related components(COL1, hyaluronan, ceramide and TGF-𝛽1). These results suggested that UA can be a developing candidate for developing alternative skin protective agent or functional food ingredient.

Mutation of rpsL Gene in Streptomycin-Resistant Pseudomonas syringae pv. actinidiae Biovar 3 Strains Isolated from Korea (국내에서 분리된 Streptomycin 저항성 Pseudomonas syringae pv. actinidiae Biovar 3 균주에서 rpsL 유전자의 돌연변이)

  • Lee, Young Sun;Kim, Gyoung Hee;Koh, Young Jin;Jung, Jae Sung
    • Research in Plant Disease
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    • v.28 no.1
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    • pp.26-31
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    • 2022
  • Pseudomonas syringae pv. actinidiae (Psa) is the causal agent responsible for the bacterial canker disease of kiwifruit plants. Psa strains are divided into five different biovars based on genetic and biochemical characteristics. Among them, biovar 2 and 3 strains of Psa were isolated and have been causing widespread damages in Korea. One of the most effective ways to control Psa is to use an antibiotic such as streptomycin. However, Psa strains resistant to this antibiotic were isolated in Korea, and an earlier study revealed that the resistance in the biovar 2 is associated with strA-strB genes. This study aimed to determine the molecular resistance mechanism of Psa biovar 3 strains to streptomycin. Sequencing the rpsL gene encoding ribosomal protein S12 from three streptomycin-resistant strains screened in the laboratory revealed that a spontaneous mutation occurred either at codon 43 or 88. Meanwhile, in four streptomycin-resistant strains of Psa biovar 3 isolated from two kiwifruit orchards, a single nucleotide in codon 43 of the rpsL, which is AAA in streptomycin-sensitive strain, was substituted for AGA causing an amino acid change from lysine to arginine. The resistant mechanism in all biovar 3 strains obtained in Korea was identified as a mutation of the rpsL gene.

Antioxidant and anti-inflammatory activities of Lathyrus japonicus ethanol extracts (갯완두(Lathyrus japonicus) 에탄올 추출물의 항산화 및 항염증 효능)

  • Yun Gyeong Park;Myeong Seok Lee;Seok-Chun Ko;Jeong Min Lee;Mi-Jin Yim;Kyung Woo Kim;Hyun-Soo Kim;Ji-Yul Kim;Chul Hwan Kim;Jung Hye Won;Dae-Sung Lee;Gun-Woo Oh
    • Journal of Marine Bioscience and Biotechnology
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    • v.15 no.1
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    • pp.1-11
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    • 2023
  • In the present study, the antioxidant and anti-inflammatory activities of ethanolic extracts from Lathyrus japonicus at concentrations of 50, 100, and 200 ㎍/mL were investigated in LPS-stimulated, RAW264.7 cells. Antioxidant properties were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays and ferric reducing antioxidant power assay. In addition, the production of reactive oxygen species (ROS) was measured using the 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe by flow cytometry. To examine the anti-inflammatory activity of the extracts of L. japonicus, their effects on the levels of nitric oxide (NO); production of cytokines such as interleukin (IL)-1β, IL-10, and tumor necrosis factor-α (TNF-α); and the activities of enzymes such as inducible NOS (iNOS) and cyclooxygenase-2 (COX-2) were assessed. The IC50 values of the DPPH and ABTS radical scavenging assays were 476.09 ± 1.50 and 34.91 ± 0.37 ㎍/mL, respectively. In addition, L. japonicus extracts not only inhibited ROS production, but also the production of NO, IL-1β, and IL-10, and the activity of iNOS in a dose-dependent manner. In summary, the ethanolic extracts of L. japonicus could be used as a functional food additive and an anti-inflammatory agent owing to their antioxidant and anti-inflammatory activities

A Study on the Flame Retardant Properties of EPDM Rubber Mixed with Phosphorus and Halogen Compound (인 및 할로겐 함유 EPDM 고무 혼합물의 난연 특성에 관한 연구)

  • Choi, Seong Su;Im, Wan-Bin;Kim, Jin Hong;Park, Young-ae W.;Woo, Je-Wan
    • Elastomers and Composites
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    • v.37 no.4
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    • pp.224-233
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    • 2002
  • This study has investigated the flame retardant properties of EPDM rubber with the addition of various flame retardants. Carbon black, stearic acid, zinc oxide cross-linking agent were mixed with EPDM rubber to produce the base rubber E0 without the addition of flame retardants. Phosphorus flame retardant Tricrecyl phosphate(TCP) was added to E0 in 0.5, 1, 1.5, 2 phr to make E1~E4 samples and red phosphorus was added in 3, 6, 9, 12 phr to make E5~E8 samples. A flame retardant of the bromine family Decabromodiphenyloxide(DBDPO), and a chlorinated paraffin retardant of the chlorine family was added to E0 in 3, 6, 9, 12 phr to make E9~E12 and E13~E16 samples, repectively. Basic physical properties such as tensile strength, tear strength and hardness were measured for all the rubber samples with various flame retardant additions. There was no substantial differences. On the other hand, Oxygen index and UL94 were measured to study flame retardant properties. From oxygen index measurements E0 sample showed a value of 23.5%, indicating the improvement of flame retardant properties. Also from UL94 measurements, it was found that addition of red phosphorus resulted in maximum flame retardant effect. It was found that increasing the amount of addition resulted in decreasing combustion rate and improving flame retardant effect regardless of the kind of flame retardant.

Evaluation of Soil Streptomyces spp. for the Biological Control of Fusarium Wilt Disease and Growth Promotion in Tomato and Banana

  • Praphat, Kawicha;Jariya, Nitayaros;Prakob, Saman;Sirikanya, Thaporn;Thanwanit, Thanyasiriwat;Khanitta, Somtrakoon;Kusavadee, Sangdee;Aphidech, Sangdee
    • The Plant Pathology Journal
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    • v.39 no.1
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    • pp.108-122
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    • 2023
  • Fusarium oxysporum f. sp. lycopersici (Fol) and Fusarium oxysporum f. sp. cubense (Foc), are the causal agent of Fusarium wilt disease of tomato and banana, respectively, and cause significant yield losses worldwide. A cost-effective measure, such as biological control agents, was used as an alternative method to control these pathogens. Therefore, in this study, six isolates of the Streptomyces-like colony were isolated from soils and their antagonistic activity against phytopathogenic fungi and plant growth-promoting (PGP) activity were assessed. The results showed that these isolates could inhibit the mycelial growth of Fol and Foc. Among them, isolate STRM304 showed the highest percentage of mycelial growth reduction and broad-spectrum antagonistic activity against all tested fungi. In the pot experiment study, the culture filtrate of isolates STRM103 and STRM104 significantly decreased disease severity and symptoms in Fol inoculated plants. Similarly, the culture filtrate of the STRM304 isolate significantly reduced the severity of the disease and symptoms of the disease in Foc inoculated plants. The PGP activity test presents PGP activities, such as indole acetic acid production, phosphate solubilization, starch hydrolysis, lignin hydrolysis, and cellulase activity. Interestingly, the application of the culture filtrate from all isolates increased the percentage of tomato seed germination and stimulated the growth of tomato plants and banana seedlings, increasing the elongation of the shoot and the root and shoot and root weight compared to the control treatment. Therefore, the isolate STRM103 and STRM104, and STRM304 could be used as biocontrol and PGP agents for tomato and banana, respectively, in sustainable agriculture.