• 제목/요약/키워드: dose model

검색결과 1,829건 처리시간 0.03초

3D Bioprinted GelMA/PEGDA Hybrid Scaffold for Establishing an In Vitro Model of Melanoma

  • Duan, Jiahui;Cao, Yanyan;Shen, Zhizhong;Cheng, Yongqiang;Ma, Zhuwei;Wang, Lijing;Zhang, Yating;An, Yuchuan;Sang, Shengbo
    • Journal of Microbiology and Biotechnology
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    • 제32권4호
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    • pp.531-540
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    • 2022
  • Due to the high incidence of malignant melanoma, the establishment of in vitro models that recapitulate the tumor microenvironment is of great biological and clinical importance for tumor treatment and drug research. In this study, 3D printing technology was used to prepare GelMA/PEGDA composite scaffolds that mimic the microenvironment of human malignant melanoma cell (A375) growth and construct in vitro melanoma micro-models. The GelMA/PEGDA hybrid scaffold was tested by the mechanical property, cell live/dead assay, cell proliferation assay, cytoskeleton staining and drug loading assay. The growth of tumor cells in two- and three-dimensional culture systems and the anti-cancer effect of luteolin were evaluated using the live/dead staining method and the Cell Counting Kit-8 (CCK-8) method. The results showed a high aggregation of tumor cells on the 3D scaffold, which was suitable for long-term culture. Cytoskeleton staining and immunofluorescent protein staining were used to evaluate the degree of differentiation of tumor cells under 2D and 3D culture systems. The results indicated that 3D bioprinted scaffolds were more suitable for tumor cell expansion and differentiation, and the tumor cells were more aggressive. In addition, luteolin was time- and dose-dependent on tumor cells, and tumor cells in the 3D culture system were more resistant to the drug.

Effects of G-Rh2 on mast cell-mediated anaphylaxis via AKT-Nrf2/NF-κB and MAPK-Nrf2/NF-κB pathways

  • Xu, Chang;Li, Liangchang;Wang, Chongyang;Jiang, Jingzhi;Li, Li;Zhu, Lianhua;Jin, Shan;Jin, Zhehu;Lee, Jung Joon;Li, Guanhao;Yan, Guanghai
    • Journal of Ginseng Research
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    • 제46권4호
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    • pp.550-560
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    • 2022
  • Background: The effect of ginsenoside Rh2 (G-Rh2) on mast cell-mediated anaphylaxis remains unclear. Herein, we investigated the effects of G-Rh2 on OVA-induced asthmatic mice and on mast cell-mediated anaphylaxis. Methods: Asthma model was established for evaluating airway changes and ear allergy. RPMCs and RBL-2H3 were used for in vitro experiments. Calcium uptake, histamine release and degranulation were detected. ELISA and Western blot measured cytokine and protein levels, respectively. Results: G-Rh2 inhibited OVA-induced airway remodeling, the production of TNF-α, IL-4, IL-8, IL-1β and the degranulation of mast cells of asthmatic mice. G-Rh2 inhibited the activation of Syk and Lyn in lung tissue of OVA-induced asthmatic mice. G-Rh2 inhibited serum IgE production in OVA induced asthmatic mice. Furthermore, G-Rh2 reduced the ear allergy in IgE-sensitized mice. G-Rh2 decreased the ear thickness. In vitro experiments G-Rh2 significantly reduced calcium uptake and inhibited histamine release and degranulation in RPMCs. In addition, G-Rh2 reduced the production of IL-1β, TNF-α, IL-8, and IL-4 in IgE-sensitized RBL-2H3 cells. Interestingly, G-Rh2 was involved in the FcεRI pathway activation of mast cells and the transduction of the Lyn/Syk signaling pathway. G-Rh2 inhibited PI3K activity in a dose-dependent manner. By blocking the antigen-induced phosphorylation of Lyn, Syk, LAT, PLCγ2, PI3K ERK1/2 and Raf-1 expression, G-Rh2 inhibited the NF-κB, AKT-Nrf2, and p38MAPK-Nrf2 pathways. However, G-Rh2 up-regulated Keap-1 expression. Meanwhile, G-Rh2 reduced the levels of p-AKT, p38MAPK and Nrf2 in RBL-2H3 sensitized IgE cells and inhibited NF-κB signaling pathway activation by activating the AKT-Nrf2 and p38MAPK-Nrf2 pathways. Conclusion: G-Rh2 inhibits mast cell-induced allergic inflammation, which might be mediated by the AKT-Nrf2/NF-kB and p38MAPK-Nrf2/NF-κB signaling pathways.

뇌전증 동물 모델에 대한 백출 추출물의 보호 효과 (Protective effects of Atractylodis Rhizoma Alba Extract on seizures mice model)

  • 강소희;이수은;이아영;서윤수;문창종;김성호;이지혜;김중선
    • 대한본초학회지
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    • 제36권6호
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    • pp.1-8
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    • 2021
  • Objectives : Atractylodis rhizoma Alba has been traditionally used as a medicinal resource that is used for enhancing Qi (氣) in traditional medicine in Korea, China, and Japan. This study investigated the protective effects of Atractylodis rhizoma Alba extract (ARE) against trimethyltin (TMT), a neurotoxin that causes selective hippocampal injury, using both in vitro and in vivo models. Methods : We investigated the effects of ARE on TMT- (5mM) induced cytotoxicity in primary cultures of mouse hippocampal cells (7 days in vitro ) and on hippocampal injury in C57BL/6 mice injected with TMT (2.6 mg/kg). Results : We observed that ARE treatment (0 - 50 ㎍/mL) significantly reduced TMT-induced cytotoxicity in cultured hippocampal neurons in a dose-dependent manner, based on results of lactate dehydrogenase and 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assays. Additionally, this study showed that orally administered ARE (5 mg/kg; between -6 and 0 days before TMT injection) significantly attenuated seizures in adult mice. Furthermore, quantitative analysis of allograft inflammatory factor-1 (Iba-1)- and glial fibrillary acidic protein (GFAP)- positive cells showed significantly reduced levels of Iba-1- and GFAP-positive cell bodies in the dentate gyrus of mice treated with ARE prior to TMT injection. These findings indicate the significant protective effects of ARE against the TMT-induced massive activation of microglia and astrocytes in the hippocampus. Conclusions : We conclude that ARE minimizes the detrimental effects of TMT-induced hippocampal neurotoxicity, both in vitro and in vivo . Our findings may serve as useful guidelines to support ARE administration as a promising pharmacotherapeutic approach to hippocampal degeneration.

A Novel Therapeutic Effect of a New Variant of CTLA4-Ig with Four Antennas That Are Terminally Capped with Sialic Acid in the CTLA4 Region

  • Piao, Yongwei;Yun, So Yoon;Kim, Hee Soo;Park, Bo Kyung;Ha, Hae Chan;Fu, Zhicheng;Jang, Ji Min;Back, Moon Jung;Shin, In Chul;Won, Jong Hoon;Kim, Dae Kyong
    • Biomolecules & Therapeutics
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    • 제30권6호
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    • pp.529-539
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    • 2022
  • Rheumatoid arthritis (RA) is a multifactorial immune-mediated disease, the pathogenesis of which involves different cell types. T-cell activation plays an important role in RA. Therefore, inhibiting T-cell activation is one of the current therapeutic strategies. Cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig), also known as abatacept, reduces cytokine secretion by inhibiting T-cell activation. To achieve a homeostatic therapeutic effect, CTLA4-Ig has to be administered repeatedly over several weeks, which limits its applicability in RA treatment. To overcome this limitation, we increased the number of sialic acid-capped antennas by genetically engineering the CTLA4 region to increase the therapeutic effect of CTLA4-Ig. N-acetylglucosaminyltransferase (GnT) and α2,6-sialyltransferase (α2,6-ST) were co-overexpressed in Chinese hamster ovary (CHO) cells to generate a highly sialylated CTLA4-Ig fusion protein, named ST6. The therapeutic and immunogenic effects of ST6 and CTLA4-Ig were compared. ST6 dose-dependently decreased paw edema in a mouse model of collagen-induced arthritis and reduced cytokine levels in a co-culture cell assay in a similar manner to CTLA4-Ig. ST6- and CTLA4-Ig-induced T cell-derived cytokines were examined in CD4 T cells isolated from peripheral blood mononuclear cells after cell killing through irradiation followed by flow- and magnetic-bead-assisted separation. Interestingly, compared to CTLA4-Ig, ST6 was substantially less immunogenic and more stable and durable. Our data suggest that ST6 can serve as a novel, less immunogenic therapeutic strategy for patients with RA.

스코폴라민으로 유도한 기억력 손상 모델에서 소엽 추출물의 보호 효과 (Perilla Frutescens Extract Protects against Scopolamine-Induced Memory Deficits in Mice)

  • 이지혜;이은홍;정은미;김동현;김성규;박미희;정지욱
    • 동의생리병리학회지
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    • 제35권3호
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    • pp.97-103
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    • 2021
  • Perilla frutescens (P. frutescens) is an important herb used for many purposes such as medicinal, aromatic, and functional food in Asian countries and has beneficial effects such as antioxidant activity, anti-inflammation activity, anti-depression activity, and anxiolytic activity. However, there have been no studies on the protective effect of P. frutescens extract (PFE) on amnesia in vivo. The present study aimed to investigate whether PFE protects memory deficit using a scopolamine-induced mice model and elucidate the underlying mechanisms involved. The protective effect of PFE against scopolamine-induced memory deficits was investigated using Y-maze, passive avoidance, and Morris water maze tests. Furthermore, the potential mechanisms of PFE in improving memory capabilities related to the cholinergic system and antioxidant activity were examined. PFE significantly increased spontaneous alternation in the Y-maze test, step-through latency in the passive avoidance test, and swimming time in the target quadrant in the probe test when compared to the scopolamine-treated group. Likewise, PFE significantly decreased escapes latency in the Morris water maze test. PFE could not regulate cholinergic function in acetylcholine level and acetylcholine esterase activity. However, PFE increased DPPH radical scavenging activity dose-dependently and total polyphenol content was 127.7±1.2 ㎍ GAE/mg. The results showed that the PFE could be a preventive and/or therapeutic candidate for memory and cognitive dysfunction in Alzheimer's disease.

C57BL/6N db/db 생쥐에서 복분자 미숙과 에탄올 추출물의 항당뇨 효과 (Antidiabetic effects of unripe black raspberry ethanol extracts in C57BL/6N db/db mice)

  • 최혜란;이수정;류태호
    • 한국식품과학회지
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    • 제54권4호
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    • pp.391-397
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    • 2022
  • 본 연구는 복분자 미숙과의 항당뇨 활성을 알아보기 위해 유전적 당뇨 질환 동물모델인 db/db 마우스에서 복분자 미숙과 50% 에탄올 추출물을 11주간 경구 투여한 후 당뇨병 개선 효과를 조사하였다. 체중 측정 결과, 정상대조군에 비하여 당뇨대조군의 체중이 45.9% 증가하였으나 복분자 미숙과 50% 에탄올 추출물을 투여한 실험군들의 체중 변화는 보이지 않았다. 시료 투여 11주 후 공복혈당을 측정했을 때 복분자 미숙과 50% 에탄올 추출물 투여군에서는 농도 의존적으로 혈당 상승이 억제되었으며, 복강내당능 시험을 통해 복분자 미숙과 50% 에탄올 추출물이 양성대조군과 유사한 경향으로 혈당을 감소시키는 것을 확인하였다. 혈중 중성지방 수치 역시 복분자 미숙과 50% 에탄올 추출물 투여군은 농도 의존적으로 중성지방의 농도가 감소되었고, 혈중 인슐린의 농도는 복분자 미숙과 50% 에탄올 추출물 투여군이 당뇨대조군보다 약간 높은 수준으로 나타났으나 군간 유의성은 없었다. 췌장의 병리조직학적 검사 결과, 당뇨대조군에서 인슐린을 분비하는 췌장의 베타세포로 이루어진 랑게르한스섬의 형태학적 손상이 나타났으며 복분자 미숙과 50% 에탄올 추출물 투여에 의해 손상이 억제됨으로써 랑게르한스섬의 면적 및 세포 수가 당뇨대조군에 비해 증가했음을 확인하였다. 또한 인슐린 항체를 이용하여 면역 염색을 통해 췌장 내 베타세포의 형태학적 구조를 확인해 보면 복분자 미숙과 50% 에탄올 추출물 투여군들에서 인슐린을 분비하는 랑게르한스섬 세포 수가 유의하게 증가되었음을 알 수 있었다. 따라서 위 결과를 종합해 볼 때 복분자 미숙과 50% 에탄올 추출물이 혈당 강하에 효과가 있으며, 이를 위한 목적으로 장기간 섭취했을 때 항당뇨에 도움이 될 것이라고 사료된다.

흰줄숲모기에 대한 5종 식물추출물의 기피효능 평가 (Repellent Activity of Five Different Plant Extracts Against Aedes albopictus)

  • 박성익;박정주;김단비;문나영;신지윤;차성경;김사라;김종식;손동철
    • 한국응용곤충학회지
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    • 제61권2호
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    • pp.369-376
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    • 2022
  • 본 연구에서는, 5가지 식물의 메탄올 추출물을 이용하여 모기기피 효과 실험을 진행하고 누드 쥐를 모델로 하여 흰줄숲모기에 대한 모기기피제의 유효용량 및 유효시간을 평가하였다. 그리고 식물의 휘발성분을 GC-MS로 분석하였다. 유효용량은 개박하가 10, 50, 100, 200 ㎍/mL에서 72.9, 83.7, 86.4, 97.3%의 효율로 가장 높았다. 누드 쥐를 대상으로 한 유효시간 연구에서는 5가지 식물의 메탄올 추출물 중 개박하, 개다래 및 개똥쑥이 90.5%로, 30분까지만 지속하였다. 각 식물의 휘발성분을 분석한 결과, 애플민트 28개 성분, 개다래 19개 성분, 개똥쑥 27개 성분, 개박하 26개 성분, 민들레 19개 성분이 확인 되었다. 특히 모기기피제의 유효 성분으로 알려진 네페탈락톤(nepetalactone)이 개박하의 휘발성분 중 한 성분으로 확인 되었다(27.95 mg/Kg). 본 연구결과는 다양한 휘발성분을 함유한 식물을 이용한 모기기피제 재료로서 가능성을 제시한다.

산화적 스트레스에 대한 천마 추출물의 신경세포 보호 및 항산화 효과 (Neuroprotective and Anti-oxidant Effects of Gastrodiae Rhizoma Extracts against Hydrogen Peroxide-induced Cytotoxicity in SH-SY5Y Cells)

  • 권강범;김하림;김예슬;박은희;최한별;류도곤
    • 동의생리병리학회지
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    • 제36권6호
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    • pp.209-212
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    • 2022
  • We recently reported that Gastrodia elata extracts (GEE) had an effects to protect against lipopolysaccharide-induced cognitive impairment in vivo model. In this study, we investigated the neuroprotective effects and the mechanism of action of GEE in hydrogen peroxide (H2O2)-induced cell death of SH-SY5Y human neuroblastoma cell. The SH-SY5Y cells were divided into five groups, including control(non-treated group), 100 μM H2O2, 100, 200, 500 ㎍/㎖ GEE+ 100 μM H2O2 groups. Pre- and co-treatment with GEE prevented cell death induced by 100 μM H2O2 for 24 h in SH-SY5Y cells. Our findings also showed that anti-oxidants enzymes (Cu/Zn superoxide dismutase, Mn superoxide dismutase, catalase) were up-regulated by 100 μM H2O2. But GEE suppressed H2O2-induced anti-oxidants enzymes decrease in a dose-dependent manner. Treatment with GEE also inhibited phosphorylation of eukaryotic initiation factor-2α (eIF-2α) and p38 by H2O2. Taken together, the neuroprotective effects of GEE in terms of recovery of antioxidant enzymes expression, down-regulation of eIF-2α and p38 phosphorylation, and inhibition of cell death are associated with reduced oxidative stress in SH-SY5Y cells.

Role of soy lecithin combined with soy isoflavone on cerebral blood flow in rats of cognitive impairment and the primary screening of its optimum combination

  • Hongrui Li;Xianyun Wang;Xiaoying Li;Xueyang Zhou;Xuan Wang;Tiantian Li;Rong Xiao;Yuandi Xi
    • Nutrition Research and Practice
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    • 제17권2호
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    • pp.371-385
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    • 2023
  • BACKGROUND/OBJECTIVES: Soy isoflavone (SIF) and soy lecithin (SL) have beneficial effects on many chronic diseases, including neurodegenerative diseases. Regretfully, there is little evidence to show the combined effects of these soy extractives on the impairment of cognition and abnormal cerebral blood flow (CBF). This study examined the optimal combination dose of SIF + SL to provide evidence for improving CBF and protecting cerebrovascular endothelial cells. MATERIALS/METHODS: In vivo study, SIF50 + SL40, SIF50 + SL80 and SIF50 + SL160 groups were obtained. Morris water maze, laser speckle contrast imaging (LSCI), and hematoxylin-eosin staining were used to detect learning and memory impairment, CBF, and damage to the cerebrovascular tissue in rat. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the oxidized glutathione (GSSG) were detected. The anti-oxidative damage index of superoxide dismutase (SOD) and glutathione (GSH) in the serum of an animal model was also tested. In vitro study, an immortalized mouse brain endothelial cell line (bEND.3 cells) was used to confirm the cerebrovascular endothelial cell protection of SIF + SL. In this study, 50 µM of Gen were used, while the 25, 50, or 100 µM of SL for different incubation times were selected first. The intracellular levels of 8-OHdG, SOD, GSH, and GSSG were also detected in the cells. RESULTS: In vivo study, SIF + SL could increase the target crossing times significantly and shorten the total swimming distance of rats. The CBF in the rats of the SIF50 + SL40 group and SIF50 + SL160 group was enhanced. Pathological changes, such as attenuation of the endothelium in cerebral vessels were much less in the SIF50 + SL40 group and SIF50 + SL160 group. The 8-OHdG was reduced in the SIF50 + SL40 group. The GSSG showed a significant decrease in all SIF + SL pretreatment groups, but the GSH showed an opposite result. SOD was upregulated by SIF + SL pretreatment. Different combinations of Genistein (Gen)+SL, the secondary proof of health benefits found in vivo study, showed they have effective anti-oxidation and less side reaction on protecting cerebrovascular endothelial cell. SIF50 + SL40 in rats experiment and Gen50 + SL25 in cell test were the optimum joint doses on alleviating cognitive impairment and regulating CBF through protecting cerebrovascular tissue by its antioxidant activity. CONCLUSIONS: SIF+SL could significantly prevent cognitive defect induced by β-Amyloid through regulating CBF. This kind of effect might be attributed to its antioxidant activity on protecting cerebral vessels.

An Examination of the Effectiveness of Crisis Response Strategies for Repairing Competence and Integrity Violations

  • Sung, Yen-yi;Lee, Han-joon;Park, Jong-chul
    • Asia Marketing Journal
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    • 제15권1호
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    • pp.129-154
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    • 2013
  • Product-harm crises, which are connected to defective or dangerous products, are perceived as the most common threats to a company. Product harm crises can distort long standing favorable equality perceptions, tarnish a company's reputation, cause major revenue and market-share losses, lead to costly product recalls, and devastate a carefully nurtured brand equity. However, in spite of the devastating impact of product-harm crises, little systematic research exists to asses its marketing consequences. So, the purpose of this study is to investigate how Koreans react to the crisis response in the aftermath of different crises(competence violation vs. integrity violation) and inspire additional research in crisis communication. This study has three main findings which run counter to the assumptions of Kim et al.(2007). Namely, the current study expands on the research of Kim et al. (2004, 2007) by examining how companies repair customers' trust and corporate attitude after crises. Different from previous studies, this study assumes that apology for an integrity-based crisis is the most appropriate way to repair consumer trust and corporate attitude. As for competence-based crisis, similarly, apology for competence-based crisis can be more successful repairing consumer trust and corporate attitude. Concerning silence strategy, remaining silent dose not admit or deny guilt right away, but instead of asking the perceiver to withhold judgment, suggesting that, silence could be expected to be superior to apology but inferior to denial. Finally, apology for competence violation will be expected to bemore effective than apology for integrity violation. Research conceptual model was as follows: According to the results, apology is found to be the most effective strategy to repair corporate attitude no matter the crisis is perceived as a violation of competence or integrity. Second, company may consider keeping silent as a desirable response because they does not admit nor deny responsibility but ask the public to withhold judgment. However, the result of this study shows that, in the overall crisis situations, silence strategy did not differ significantly from the denial strategy, which suggested that the public wants explanation instead of uncertainty. Third, there was the interaction effect between crisis type and crisis response strategies. In this study, apology is more effective for the competence violated situation in terms of regaining consumer trust and repairing their attitude toward company, while the apology's effectiveness is lower for the integrity-violated situation. More specifically, when the crisis is perceived due to company's lack of ability(competence violation), consumer's trust belief and attitude toward the company is more easily to repair when the company issued a sincere apology. Damaged product is perceived less intentional so participants are more likely to give the company second chance when they apology to the public. By contrast, exaggerated advertisement(integrity violation) is perceived intentionally and thus makes participants angrier toward the accused company. Although apology is perceived as the most effective strategy, when issuing apology, it also means the company admitted their intention. Therefore, in this kind of crisis situation, trust repair needs not only a sincere apology but additional efforts.

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