• Title/Summary/Keyword: release treatment

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Development of PLGA Nanoparticles for Astrocyte-specific Delivery of Gene Therapy: A Review (별아교세포 선택적 유전자 치료전달을 위한 PLGA 나노입자 개발)

  • Shin, Hyo Jung;Lee, Ka Young;Kwon, Kisang;Kwon, O-Yu;Kim, Dong Woon
    • Journal of Life Science
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    • v.31 no.9
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    • pp.849-855
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    • 2021
  • Recently, as nanotechnology has been introduced and used in various fields, the development of new drugs has been accelerating. Nanoparticles have maintained blood drug concentration for extended periods of time with a single administration of the drug. The drug can then be selectively released only at the pathological site, thereby reducing side effects to other non-pathological sites. In addition, nanoparticles can be modified for selective target sites delivery for other specific diseases, with polymers being widely used in the manufacture of these nanoparticles. Poly (D,L-lactic-co-glycolic acid ) (PLGA) is one of the most extensively developed biodegradable polymers. PLGA is widely used in drug delivery for a variety of applications. It has also been approved by the FDA as a drug delivery system and is widely applied in controlled release formulations, such as in gene therapy treatments. PLGA nanoparticles have been developed as delivery systems with high efficiency to specific cell types by using passive and active targeting methods. After the development of a drug delivery system using PLGA nanoparticles, the drug is selectively delivered to the target site, and the effective blood concentration for extended periods of time is optimized according to the disease. In this review paper, we focus on ways to improve cell-specific treatment outcomes by examining the development of astrocyte selective nanoparticles based on PLGA nanomaterials for gene therapy.

A Study on Knowledge, Attitude, Infection Management Intention & Educational needs of New Respiratory Infectious Disease among Nurses who unexperienced NRID(SARS & MERS) (신종호흡기감염병(SARS와 MERS) 간호경험이 없는 간호사의 신종호흡기감염병에 대한 지식, 태도, 감염관리활동 의도와 교육요구도)

  • Choi, Young-Eun;Lee, Eun-Sook
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.20 no.2
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    • pp.721-731
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    • 2019
  • The purpose of this study was to investigate the knowledge, attitude, infection management intention and educational needs among nurses with no experience of new respiratory infectious diseases (NRID: SARS and MERS). Data were collected from 162 nurses working at the general hospitals in B city using structured questionnaires from October 10 to 31, 2017. The infection management intention of NRID was high in those who were over 30 years old, married, highly educated, and had a total working experience of more than 5 years. Nurses' infection management intention for NRID showed a positive correlation between knowledge of NRID (r=.27, p<.001) and attitude toward NRID (r=.65, p<.001). In other words, the higher the knowledge score for NRID, the more positive the attitude and the higher the infection management intention. In addition, the knowledge score related to incubation period, treatment, isolation, and release criteria was low while the educational needs were high. Therefore, in preparation for the possibility of NRID relapse and other NRID in the future, a systematic program addressing these educational needs for nurses should be periodically implemented to enhance infection management.

Baicalein induces cell death in Human Lung Carcinoma A549 Cells: Role of Apoptosis and Autophagy pathway (인체폐암 A549 세포에서 Baicalein에 의한 세포사멸 유도: Apoptosis와 Autophagy 경로의 역할)

  • Kim, Chul Hwan;Hwang, Buyng Su;Jeong, Yong Tae;Kim, Min-Jin;Shin, Su Young;Oh, Young Taek;Eom, Jung Hye;Lee, Seung Young;Choi, Kyung Min;Cho, Pyo Yun;Jeong, Jin-Woo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.04a
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    • pp.112-112
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    • 2019
  • Baicalein is one of the main flavonoids derived from roots of Scutellaria baicalensis Georgi, a traditional Oriental medicine. Although baicalein has high antitumor effect on several human carcinomas, the mechanism responsible for this property is not unclear. In this study, the data revealed that baicale-ininduced growth inhibition was associated with the induction of apoptosis connecting with cytochrome c release, down-regulation of anti-apoptotic Bcl-xl and increased the percentage of cells with a loss of mitochondria membrane permeabilization. Baicalein also induced the proteolytic activation of caspases and cleavage of PARP; however, blockage of caspases activation by z-VAD-fmk inhibited baicalein-induced apoptosis. In addition, baicalein enhanced the formation of autophagosomes and up-regulated LC3-II/LC3-I ratio. Interestingly, the pretreatment of bafilomycin A1 recovered baicalein-induced cell death suggesting that autophagy by baicalein roles as protective autophagy. Taken together, our results indicated that this flavonoid induces apoptosis and cell protective autophagy. These data means combination treatment with baicalein and autophagy inhibitor might be a promising anticancer drug.

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Application of Molecular Diagnostics Technology in the Development of a Companion Diagnostics for Malignant Solid Tumors (악성 고형암의 항암제 동반진단 기술에서 분자진단기술의 적용)

  • Kim, Jin-Hee
    • The Journal of the Korea Contents Association
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    • v.19 no.3
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    • pp.365-374
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    • 2019
  • Unlike benign tumors, malignant tumors are capable of metastasis, easy to relapse, poor survival, and low quality of life. In Korea, here is a tendency to treat the tumors collectively according to the General Principles of Cancer Chemotherapy(GPCC) of the Health Insurance Review & Assessment Service (HIRA). But recently, companion diagnostics(CDx) is recommended rather than unilateral medication because biomarker-based molecular diagnostics is possible to predict the drug response of patients before drug treatment. Not only domestic but also overseas Food and Drug Administratio (FDA) recommends the development of the CDx system at the stage of drug development to ensure the responsiveness and safety of medicines. In this study, I focused on the necessity of CDx development direction as well as CDx development status through literature review. Furthermore I also discussed CDx types according to the molecular diagnostic technology such as immunohistochemistry (IHC), polymerase chain reaction (PCR), in situ hybridization (ISH), and next-generation sequencing (NGS) not only in the approved CDx but also in the developing one by US FDA. And I suggested the technology issue of CDx development process such as a selection of molecular diagnostics at the time of release, a clear understanding of the CDx mechanism, and a convergence of drug with CDx development. The necessity of social insurance system also was proposed for CDx development.

Maintenance of Platelet Counts with Low Level QC Materials and the Change in P-LCR according to Hemolysis with XN-9000 (XN-9000장비에서 Low Level QC물질에서의 혈소판 수 관리와 용혈에 따른 P-LCR의 변화)

  • Shim, Moon-Jung;Lee, Hyun-A
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.4
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    • pp.399-405
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    • 2018
  • The platelet count in clinical laboratories is essential for the diagnosis and treatment of hemostasis abnormalities, and accurate platelet counting in the low count range is of prime importance for deciding if a platelet transfusion is needed and for monitoring after chemotherapy. Quality control is designed to reduce and correct any deficiencies in the internal analytical process of a clinical laboratory prior to the release of patient results. Fragmented erythrocytes are the major confusing factors for platelet counting because of their similar size to platelets. The authors found that the low range QC values were out of 2SD with a Sysmex automatic analyzer in internal quality control process. Thus far, there has been little discussion on the relationship between hemolysis and the platelet parameters. Therefore, this study focused on the performance of automated platelet counts, including the PLT-F, the PLT-I, and PLT-O methods at the low platelet range using the low level QC materials and compared the 5 platelet parameters with the hemolyzed samples. The results showed that the CV was the smallest with PLT-F and P-LCR increased from 18.4 to 31.9% in the hemolysis samples. These results indicate that a more accurate estimation of the platelet counts can be achieved using the PLT-F method than the PLT-I method at the low platelet range. The use of the PLT-F system improves the confidence of results in low platelets samples in a routine hematology laboratory. The results suggest that P-LCR is a new parameter in assessing samples when the specimen is suspected of hemolysis and deterioration. Nevertheless, further studies will be needed to establish the relationship with P-LCR and hemolysis using human blood specimens.

Effect of Semisulcospira libertina Extract on Hepatic Injury Induced by D-galactosamine (다슬기 추출물이 D-galactosamine에 의해 손상된 간에 미치는 효과)

  • Park, Young Mi;Lee, Jong Eun;Seo, Eul Won
    • Korean Journal of Environmental Biology
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    • v.36 no.4
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    • pp.498-506
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    • 2018
  • The purpose of this study is to examine the restorative effect of Semisulcospira libertina extract, on damaged liver cells induced by D-galactosamine in rats. Treatment of damaged liver cells with S. libertina extract significantly reduced local fatty degeneration, and inflammatory cell necrosis, to levels similar with the undamaged control group. In addition, S. libertina extracts were found to reduce plasma levels of liver damage indicator enzymes, such as AST, ALT, LDH and ALP, to control levels. It also reduced lipid peroxides, and lipid contents within damaged liver tissues. This suggests that S. libertina extract has a restorative effect on liver cells, thus reducing release of damage-associated liver enzymes, and oxidative degradation of lipids. Also, S. libertina extracts were found to be involved in recovery of damaged cells from inflammatory response by suppressing expression of $TNF-{\alpha}$, which leads to tissue injury and necrosis, whereas inducing expression of HO-1 that protects cells during inflammation. Thus, S. libertina extract restores liver tissue from necrosis and fibrosis, as well modulates expression of inflammation-related genes against liver damage. Our findings suggest that S. libertina extract is an effective medicinal resource, for improving and recovering liver cells from hepatic injury.

Detrimental effects of lipopolysaccharides on maturation of bovine oocytes

  • Zhao, Shanjiang;Pang, Yunwei;Zhao, Xueming;Du, Weihua;Hao, Haisheng;Zhu, Huabin
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.8
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    • pp.1112-1121
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    • 2019
  • Objective: Gram-negative bacteria lipopolysaccharide (LPS) has been reported to be associated with uterine impairment, embryonic resorption, ovarian dysfunction, and follicle retardation. Here, we aimed to investigate the toxic effects of LPS on the maturation ability and parthenogenetic developmental competence of bovine oocytes. Methods: First, we developed an in vitro model to study the response of bovine cumulusoocyte complexes (COCs) to LPS stress. After incubating germinal vesicle COCs in $10{\mu}g/mL$ of LPS, we analyzed the following three aspects: the expression levels of the LPS receptor toll-like receptor 4 (TLR4) in COCs, activities of intracellular signaling protein p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-${\kappa}B$); and the concentrations of interleukin (IL)-$1{\beta}$, tumor necrosis factor (TNF)-${\alpha}$, and IL-6. Furthermore, we determined the effects of LPS on the maturation ability and parthenogenetic developmental competence of bovine oocytes. Results: The results revealed that LPS treatment significantly elevated TLR4 mRNA and protein expression levels in COCs. Exposure of COCs to LPS also resulted in a marked increase in activity of the intracellular signaling protein p-p38 MAPK and NF-${\kappa}B$. Furthermore, oocytes cultured in maturation medium containing LPS had significantly higher concentrations of the proinflammatory cytokines IL-$1{\beta}$, TNF-${\alpha}$, and IL-6. LPS exposure significantly decreased the first polar body extrusion rate. The cytoplasmic maturation, characterized by polar body extrusion and distribution of peripheral cortical granules, was significantly impaired in LPS-treated oocytes. Moreover, LPS exposure significantly increased intracellular reactive oxygen species levels and the relative mRNA abundance of the antioxidants thioredoxin (Trx), Trx2, and peroxiredoxin 1 in oocytes. Moreover, the early apoptotic rate and the release of cytochrome C were significantly increased in response to LPS. The cleavage, morula, and blastocyst formation rates were significantly lower in parthenogenetically activated oocytes exposed to LPS, while the incidence of apoptotic nuclei in blastocysts was significantly increased. Conclusion: Together, these results provide an underlying mechanism by which LPS impairs maturation potential in bovine oocytes.

Suppression of Lipopolysaccharide-Induced Inflammatory and Oxidative Response by 5-Aminolevulinic Acid in RAW 264.7 Macrophages and Zebrafish Larvae

  • Ji, Seon Yeong;Cha, Hee-Jae;Molagoda, Ilandarage Menu Neelaka;Kim, Min Yeong;Kim, So Young;Hwangbo, Hyun;Lee, Hyesook;Kim, Gi-Young;Kim, Do-Hyung;Hyun, Jin Won;Kim, Heui-Soo;Kim, Suhkmann;Jin, Cheng-Yun;Choi, Yung Hyun
    • Biomolecules & Therapeutics
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    • v.29 no.6
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    • pp.685-696
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    • 2021
  • In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.

Benzo[a]pyrene Cytotoxicity Tolerance in Testicular Sertoli Cells Involves Aryl-hydrocarbon Receptor and Cytochrome P450 1A1 Expression Deficiencies

  • Kim, Jin-Tac;Park, Ji-Eun;Lee, Seung-Jin;Yu, Wook-Joon;Lee, Hye-Jeong;Kim, Jong-Min
    • Development and Reproduction
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    • v.25 no.1
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    • pp.15-24
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    • 2021
  • Benzo[a]pyrene (B[a]P) is a potent carcinogen and is classified as an endocrine-disrupting chemical. In mammalian testes, Sertoli cells support spermatogenesis. Therefore, if these cells are negatively affected by exposure to xenotoxic chemicals, spermatogenesis can be seriously disrupted. In this context, we evaluated whether mouse testicular TM4 Sertoli cells are susceptible to the induction of cytotoxicity-mediated cell death after exposure to B[a] P in vitro. In the present study, while B[a]P and B[a]P-7,8-diol were not able to induce cell death, exposure to BPDE resulted in cell death. BPDE-induced cell death is accompanied by the activation of caspase-3 and caspase-7. Depolarization of the mitochondrial membrane and cytochrome c release from mitochondria were observed in benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-treated cells. These results indicate that TM4 cells are susceptible to apoptosis in a caspase-dependent manner. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that aryl hydrocarbon receptor (AhR) expression was almost undetectable in TM4 cells and that its expression was not altered after B[a]P treatment. This indicates that TM4 cells are nearly AhR-deficient. In TM4 cells, the CYP1A1 protein and its activity were not present. From these results, it is clear that AhR may be a prerequisite for CYP1A1 expression in TM4 cells. Therefore, TM4 cells can be referred to as CYP1A1-deficient cells. Thus, TM4 Sertoli cells are believed to have a rigid and protective cellular machinery against genotoxic agents. In conclusion, it is suggested that tolerance to B[a]P cytotoxicity is associated with insufficient AhR and CYP1A1 expression in testicular Sertoli cells.

In vitro Anti-oxidant and Anti-inflammatory Effects of Moringa Folium and Eucommiae Cortex 2:1 (g/g) Mixed Formula (모링가:두충 2:1 (g:g) 복합 조성물의 in vitro 항산화 및 항염 효능 연구)

  • Heo, Seok-Mo;Yang, Jin-Won;Kim, Jong-Lae;Park, Mi-Ryeong;Kim, Tae Gi;Ku, Sae-Kwang;Park, Soo-Jin
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.36 no.4
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    • pp.125-129
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    • 2022
  • The purpose of study is to evaluate in vitro anti-oxidant and anti-inflammatory effects of Moringa Folium and Eucommiae Cortex 2:1 (g/g) mixtures (MEMix). HaCaT and human normal dermal fibroblast were treated with 0.01-1 mg/mL of MEMix to monitor cytotoxicity. Radical scavenging activities of MEMix were examined by DPPH assay. To explore anti-inflammatory effect, Raw 264.7 cells were pretreated with MEMix for 1h and subsequently exposed to LPS for 18h. NO release and cytotoxicity of Raw 264.7 cells were measured by adding Griess and MTT reagents, respectively. TNF-α, IL-1β, IL-6, and PGE2 productions were examined by ELISA. Immunoblot analysis was conducted to examine COX-2 expression in MEMix pretreated Raw 264.7 cells. Up to 1 mg/mL concentration, treatment of MEMix for 24 h did not affect normal dermal fibroblast viability and significantly reduced cell viability of HaCaT cells with no concentration dependency. MEMix increased DPPH radical scavenging activity with concentration dependency. Radical scavenging activities by 1 mg/mL of MEMix was comparable with 30 µM of trolox. Pretreatment of MEMix did not change the reduction of Raw 264.7 cell viability. Exposure of LPS in Raw 264.7 cells significantly increased NO, TNF-α, IL-1β, IL-6, and PGE2 productions, and MEMix pretreatment attenuated these productions by LPS concentration dependently. However, pretreatment with MEMix did not change COX-2 expression by LPS in Raw 264.7 cells. MEMix showed in vitro anti-oxidant and anti-inflammatory activities. MEMix would be useful candidate agent against inflammation.