• 한국임상약학회지
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• 제25권3호
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• pp.138-144
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• 2015

Objective: It is to evaluate the drug interaction monitoring program as a pilot project to develop a pharmaceutical care model in a medical intensive care unit and to analyze the influencing factors of drug interactions. Method: Electronic medical records were retrospectively investigated for 116 patients who had been hospitalized in a medical intensive care unit from October to December in 2014. The prevalence of adverse reaction with risk rating higher than 'D' was investigated by Lexi-$Comp^{(R)}$ Online database. The factors related with potential drug interaction and with treatment outcomes were analyzed. Results: The number of patients with a potential interaction of drug combination was 92 (79.3%). Average ages, the length of stay in the intensive care unit and the numbers of prescription drugs showed significant differences between drug interaction group and non-drug interaction group. Opioids (14.4%), antibiotics (7.2%), and diuretics (7.2%) were most responsible drug classes for drug interactions and the individual medications included furosemide (6.4%), tramadol (4.9%), and remifentanil (4.5%). There were 950 cases with a risk rating of 'C' (84.6%), 142 cases with a risk rating of 'D' (12.6%), and 31 cases with a risk rating of 'X' (avoid combination) (2.8%). The factors affecting drug interactions were the number of drugs prescribed (p < 0.0001) and the length of stay at intensive care unit (p < 0.01). The patients in intensive care unit showed a high incidence of adverse reactions related to potential drug interaction. Therefore, drug interaction monitoring program as a one of pharmaceutical care services was successfully piloted and it showed to prevent adverse reaction and to improve therapeutic outcomes. Conclusion: Active participation of a pharmacist in the drug management at the intensive care unit should be considered.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6481-6486
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• 2013

Background: Our previous study demonstrated cytotoxicity of a crude extract from Patrinia heterophylla Bunge (PHEB). In the present study, we aimed to investigate the effects of isovaltrate acetoxyhydrin (IA) isolated from PHEB on the gastric cancer cell SGC-7901, in order to explore a potential treatment for gastric cancer. Methods: MTT assays were employed to determine the effects of IA on cell vitality and proliferation, with monitoring of cell morphology changes and examination of apoptosis with Annexin V-PI staining. Flow cytometry was used to assess cell cycle progression and mitochondrial membrane potential. The activity of caspase 3, 9 was evaluated by spectrophotometry, and the protein levels of Bax, Bcl2 and Cyclin B1 were analyzed with Western blotting of total proteins extracted from cultured cells. Results: The results demonstrated direct toxicity of IA towards SGC-7901 cells. Evidence of apoptosis included blebbing and chromatin condensation. Annexin V-PI assays revealed early apoptosis, involving rapid depolarization of mitochondrial membranes and activity of caspase 3, 9 signaling pathways. Western blotting showed that Bcl2 and Bax proteins was down- and up-regulated, respectively, and cyclin B1 was up-regulated. Cell cycle analysis further indicated that IA could induce G2/M phase arrest in SGC-7901 cells. Conclusions: In conclusion, we believe that IA induces apoptosis of SGC-7901 cells, therefore providing a potential therapeutic agent for treatment of gastric cancer.

• 한국자원식물학회지
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• 제30권6호
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• pp.640-646
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• 2017

In this study, we elucidated anti-cancer activity and potential molecular mechanism of 70% ethanol extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) (TR-E70) against human colorectal cancer cells. Anti-cell proliferative effect of TR-E70 was evaluated by MTT assay. The effect of TR-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. TR-E70 suppressed the proliferation of human colorectal cancer cell lines, HCT116 and SW480. Although TR-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by TR-E70 more dramatically occurred than that of cyclin D1 mRNA. Cyclin D1 downregulation by TR-E70 was attenuated in presence of MG132. In addition, TR-E70 phosphorylated threonine-286 (T286) of cyclin D1. TR-E70-mediated cyclin D1 degradation was blocked in presence of LiCl as an inhibitor $GSK3{\beta}$ but not PD98059 as an ERK1/2 inhibitor and SB203580 as a p38 inhibitor. Our results suggest that TR-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through $GSK3{\beta}$-dependent cyclin D1 degradation. From these findings, TR-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

• 재활치료과학
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• 제1권1호
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• pp.39-56
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• 2012

서론 : 동물 연구는 작업치료에 직접적으로 적용할 수 없으나, 인간을 대상으로 한 연구와 함께 작업치료의 이론과 임상에 필수적인 지식을 제공한다. 본 논문의 목적은 신경과학적 관점에서 동물모델이 작업치료의 이론과 임상에 어떠한 가능성을 가져다 줄 수 있는지를 살펴보는 것이다. 본론 : 동물 모델을 통해 얻은 지식은 뇌신경 질환의 기전과 관련된 신경 회로에 대한 이해를 돕는다. 이러한 지식을 바탕으로, 연구자들은 뇌신경 질환에 대한 여러 가지 가정들을 동물 모델을 통해 확인해 볼 수 있다. 또한, 여러 동물 실험들을 통해 쌓인 지식들은 인간에게 적용할 수 있는 새로운 치료적 접근들을 제시해 줄 수 있으며 치료에 대한 효율성을 높여줄 수 있다. 결론 : 동물 모델을 통해 얻은 지식은 뇌신경 질환의 기전과 관련된 신경 회로에 대한 이해를 돕는다. 이러한 지식을 바탕으로, 연구자들은 뇌신경 질환에 대한 여러 가지 가정들을 동물 모델을 통해 확인해 볼 수 있다. 또한, 여러 동물 실험들을 통해 쌓인 지식들은 인간에게 적용할 수 있는 새로운 치료적 접근들을 제시해 줄 수 있으며 치료에 대한 효율성을 높여줄 수 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3573-3577
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• 2015

Background: Sirtuin7 (SIRT7) is a type of nicotinamide adenine dinucleotide oxidized form (NAD+)-dependent deacetylase and the least understood member of the sirtuins family; it is implicated in various processes, such as aging, DNA damage repair and cell signaling transduction. There is some evidence that SIRT7 may function as a tumor trigger for human malignancy. Here, we aimed to explore the biological function of SIRT7 in ovarian carcinoma cells and its potential mechanism. Materials and Methods: Expression of SIRT7 in ovarian cancer cell lines was detected by western blotting. Transduced cell lines with SIRT7 knockdown or overexpression were constructed. Cell viability, cologenic, apoptosis-associated and motility assays were performed to elucidate the biological function of SIRT7 in ovarian cancer cells. Results: SIRT7 demonstrated a higher level in ovarian cancer cell lines compared with normal cells. On the one hand, down-regulation of SIRT7 significantly reduced ovarian cancer cell growth, repressed colony formation and increased cancer cell apoptosis; on the other hand, up-regulation promoted the migration of cancer cells. Additionally, repression of SIRT7 also induced change in apoptosis-related molecules and subunits of the NF-${\kappa}B$ family. Conclusions: In the present study, our data indicated that SIRT7 might play a role of oncogene in ovarian malignancy and be a potential therapeutic target.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10847-10853
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• 2015

Background: Lapatinib, a dual tyrosine kinase inhibitor that interrupts the epidermal growth factor receptor (EGFR) and HER2/neu pathways, has been indicated to have significant efficacy in treating HER2-positive breast cancer. However, acquired drug resistance has become a very serious clinical problem that hampers the use of this agent. In this study, we aimed to screen small molecule drugs that might reverse lapatinib-resistance of breast cancer by exploring differentially expressed genes (DEGs) via a bioinformatics method. Materials and Methods: We downloaded the gene expression profile of BT474-J4 (acquired lapatinib-resistant) and BT474 (lapatinib-sensitive) cell lines from the Gene Expression Omnibus (GEO) database and selected differentially expressed genes (DEGs) using dChip software. Then, gene ontology and pathway enrichment analyses were performed with the DAVID database. Finally, a connectivity map was utilized for predicting potential chemicals that reverse lapatinib-resistance. Results: A total of 1, 657 DEGs were obtained. These DEGs were enriched in 10 pathways, including cell cycling, regulation of actin cytoskeleton and focal adhesion associate examples. In addition, several small molecules were screened as the potential therapeutic agents capable of overcoming lapatinib-resistance. Conclusions: The results of our analysis provided a novel strategy for investigating the mechanism of lapatinib-resistance and identifying potential small molecule drugs for breast cancer treatment.

• Natural Product Sciences
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• 제17권3호
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• pp.250-255
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• 2011

The immune system is finely balanced by the activities of pro-inflammatory and anti-inflammatory mediators or cytokines. Unregulated activities of these mediators can lead to the development of various inflammatory diseases. A variety of safe and effective anti-inflammatory agents are available with many more drugs under development. Of the natural compounds, the sesquiterpenes (nootkatone, ${\alpha}$-cyperone, valencene and ${\alpha}$-selinene) isolated from C. rotundus L. have received much attention because of their potential antiinflammatory effects. However, limited studies have been reported regarding the influence of sesquiterpene structure on anti-inflammatory activity. In the present study, the anti-inflammatory potential of four structurally divergent sesquiterpenes was evaluated in lipopolysaccaride (LPS)-stimulated RAW 264.7 cells, murine macrophages. Among the four sesquiterpenes, ${\alpha}$-cyperone and nootkatone, showed stronger anti-inflammatory and a potent NF-${\kappa}B$ inhibitory effect on LPS-stimulated RAW 264.7 cells. Molecular analysis revealed that various inflammatory enzymes (iNOS and COX-2) were reduced significantly and this correlated with downregulation of the NF-${\kappa}B$ signaling pathway. Additionally, electrophoretic mobility shift assays (EMSA) elucidated that nootkatone and ${\alpha}$-cyperone dramatically suppressed LPS-induced NF-${\kappa}B$-DNA binding activity using 32Plabeled NF-${\kappa}B$ probe. Hence, our data suggest that ${\alpha}$-cyperone and nootkatone are potential therapeutic agents for inflammatory diseases.

• Natural Product Sciences
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• 제22권1호
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• pp.70-75
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• 2016

A phytoformula containing the root barks of Morus alba, the fructus of Schizandra sinensis and the roots of Asparagus cochinchinensis (MSA) was prepared as a potential new herbal remedy, and its therapeutic potential for alleviating inflammatory lung conditions was examined. For in vivo evaluation, an animal model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice was used. With oral administration of 6 - 60 mg/kg, MSA potently and dose-dependently inhibited bronchitis-like symptoms in acute lung injury induced by intranasal treatment of LPS as judged by the number of cells in the bronchoalveolar lavage fluid (BALF) and histological observation. The inhibitory potency was comparable with that of dexamethasone. For in vitro assay, the effects on the production of proinflammatory molecules in lung epithelial cells and alveolar macrophages were examined. Although MSA inhibited IL-6 production in IL-$1{\beta}$-treated lung epithelial cells (A549) only at a high concentration ($300{\mu}g/ml$), the formula strongly and concentration-dependently inhibited NO production in LPS-treated alveolar macrophages (MH-S) at $20-300{\mu}g/ml$. Based on all of these findings, the new phytoformula MSA is suggested to have the potential to control inflammatory lung diseases including bronchitis, at least in part, by inhibiting inducible nitric oxide synthase-catalyzed NO production.

• Asian Spine Journal
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• 제12권6호
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• pp.998-1009
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• 2018

Study Design: Olfactory ensheathing cells (OECs) from rat olfactory mucosa were cultured, characterized, and transplanted into a rat model of spinal cord injury (SCI). Purpose: To evaluate different doses of OECs in a rat model of SCI. Overview of Literature: SCI causes permanent functional deficit because the central nervous system lacks the ability to perform spontaneous repair. Cell therapy strategies are being explored globally. The clinical use of human embryonic stem cell is hampered by ethical controversies. Alternatively, OECs are a promising cell source for neurotransplantation. This study aimed to evaluate the efficacy of different doses of allogenic OEC transplantation in a rat model of SCI. Methods: OECs were cultured from the olfactory mucosa of Albino Wistar rats; these cells were characterized using immunohistochemistry and flow cytometry. Rats were divided into five groups (n=6 rats each). In each group, different dosage ($2{\times}10^5$, $5{\times}10^5$, $10{\times}10^5$, and >$10{\times}10^5$) of cultured cells were transplanted into experimentally injured spinal cords of rat models. However, in the SCI group, only DMEM (Dulbecco's modified Eagle's medium) was injected. Rats were followed up upto 8 weeks post-transplantation. The outcome of transplantation was assessed using the Basso, Beattie, Bresnahan (BBB) scale; motor-evoked potential studies; and histological examination. Results: Cultured cells expressed 41% of p75NTR, a marker for OEC, and 35% of anti-fibronectin, a marker for olfactory nerve fibroblast. These cells also expressed $S100{\beta}$ and glial fibrillary acid protein of approximately 75% and 83%, respectively. All the transplanted groups showed promising BBB scores for hind-limb motor recovery compared with the SCI group (p<0.05). A motor-evoked potential study showed increased amplitude in all the treated groups compared with the SCI. Green fluorescent protein-labeled cells survived in the injured cord, suggesting their role in the transplantation-mediated repair. Transplantation of $5{\times}10^5$ cells showed the best motor outcomes among all the doses. Conclusions: OECs demonstrated a therapeutic effect in rat models with the potential for future clinical applications.

• Journal of Microbiology and Biotechnology
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• 제29권7호
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• pp.1022-1032
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• 2019

Probiotics are known to provide the host with immune-modulatory effects and are therefore of remarkable interest for therapeutic and prophylactic applications against various disorders, including inflammatory diseases. Weissella cibaria JW15 (JW15) has been reported to possess probiotic and antioxidant properties. However, the effect of JW15 on inflammatory responses has not yet been reported. Therefore, the objective of the current study was to evaluate the anti-inflammatory potential of JW15 against lipopolysaccharide (LPS) stimulation. The production of pro-inflammatory factors and the cellular signaling pathways following treatment with heat-killed JW15 was examined in LPS-induced RAW 264.7 cells. Treatment with heat-killed JW15 decreased nitric oxide and prostaglandin $E_2$ production via down-regulation of the inducible nitric oxide synthase and cyclooxygenase-2. In addition, treatment with heat-killed JW15 suppressed the expression of pro-inflammatory cytokines, interleukin $(IL)-1{\beta}$, IL-6, and tumor necrosis factor-${\alpha}$. The anti-inflammatory properties of treating with heat-killed JW15 were associated with mitogen-activated protein kinase signaling pathway-mediated suppression of nuclear factor-${\kappa}B$. These results indicated that JW15 possesses anti-inflammatory potential and provide a molecular basis regarding the development of functional probiotic products.