• Journal of Microbiology and Biotechnology
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• 제24권9호
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• pp.1216-1225
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• 2014

Biofilm-related infections of Candida albicans are a frequent cause of morbidity and mortality in hospitalized patients, especially those with immunocompromised status. Options of the antifungal drugs available for successful treatment of drug-resistant biofilms are very few, and as such, new strategies need to be explored against them. The aim of this study was to evaluate the efficacy of phenylpropanoids of plant origin against planktonic cells, important virulence factors, and biofilm forms of C. albicans. Standard susceptibility testing protocol was used to evaluate the activities of 13 phenylpropanoids against planktonic growth. Their effects on adhesion and yeast-to-hyphae morphogenesis were studied in microplate-based methodologies. An in vitro biofilm model analyzed the phenylpropanoid-mediated prevention of biofilm development and mature biofilms using XTT-metabolic assay, crystal violet assay, and light microscopy. Six molecules exhibited fungistatic activity at ${\leq}0.5mg/ml$, of which four were fungicidal at low concentrations. Seven phenylpropanoids inhibited yeast-to-hyphae transition at low concentrations (0.031-0.5 mg/ml), whereas adhesion to the solid substrate was prevented in the range of 0.5-2 mg/ml. Treatment with ${\leq}0.5mg/ml$ concentrations of at least six small molecules resulted in significant (p < 0.05) inhibition of biofilm formation by C. albicans. Mature biofilms that are highly resistant to antifungal drugs were susceptible to low concentrations of 4 of the 13 molecules. This study revealed phenylpropanoids of plant origin as promising candidates to devise preventive strategies against drug-resistant biofilms of C. albicans.

• Journal of Gastric Cancer
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• 제20권1호
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• pp.29-40
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• 2020

Purpose: Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either KIT or platelet-derived growth factor receptor A (PDGFRA) and are highly responsive to several selective tyrosine kinase inhibitors. In this study, a targeted next-generation sequencing (NGS) assay with an Oncomine Focus Assay (OFA) panel was used for the genetic characterization of molecular targets in 30 Korean patients with GIST. Materials and Methods: Using the OFA that enables rapid and simultaneous detection of hotspots, single nucleotide variants (SNVs), insertion and deletions (Indels), copy number variants (CNVs), and gene fusions across 52 genes relevant to solid tumors, targeted NGS was performed using genomic DNA extracted from formalin-fixed and paraffin-embedded samples of 30 GISTs. Results: Forty-three hotspot/other likely pathogenic variants (33 SNVs, 8 Indels, and 2 amplifications) in 16 genes were identified in 26 of the 30 GISTs. KIT variants were most frequent (44%, 19/43), followed by 6 variants in PIK3CA, 3 in PDGFRA, 2 each in JAK1 and EGFR, and 1 each in AKT1, ALK, CCND1, CTNNB1, FGFR3, FGFR4, GNA11, GNAQ, JAK3, MET, and SMO. Based on the mutation types, majority of the variants carried missense mutations (60%, 26/43), followed by 8 frameshifts, 6 nonsense, 1 stop-loss, and 2 amplifications. Conclusions: Our study confirmed the advantage of using targeted NGS with a cancer gene panel to efficiently identify mutations associated with GISTs. These findings may provide a molecular genetic basis for developing new drugs targeting these gene mutations for GIST therapy.

• 한국축산식품학회지
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• 제38권3호
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• pp.515-529
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• 2018

The present study was designed to investigate the effects of calpain system on the formation of volatile flavor compounds in Hanwoo beef. In the first experiment (exp.1), Longissimus lumborum (LL) muscle samples were injected with solutions containing 50 mM $CaCl_2$ or 50 mM $ZnCl_2$ and 154 mM NaCl respectively, and aged for 7 d at $4^{\circ}C$. In the second experiment (exp.2), the ground LL muscle was incubated with the aforementioned solutions containing cathepsin inhibitor. The injection with $CaCl_2$ solution greatly elevated the calpain activity and concomitantly, significantly decreased the Warner-Bratzler shear force (p<0.05). The pH, meat color and cooking loss did not differ (p>0.05) between the treatment groups. A total of 51 volatile compounds were identified using the solid phase microextraction with gas chromatography (SPME-GC). Results on volatile analyses from the both experiments showed that the injection with calcium ions led to significant increase (p<0.05) concentrations of pyrazines and sulfuric compounds. These results coincide with a higher rate of protein degradation due to the $CaCl_2$ injection as compared to the control group. Significantly (p<0.05) higher levels of lipid oxidation derived-aldehydes were found in the samples with $ZnCl_2$. The exp.1 showed that cathepsin inhibitors had no effect on the formation of volatile flavor components after 7 d of aging. These results imply that the proteolytic activity of the calpain system is associated with generation of volatile compounds of chiller-aged beef, while the role of cathepsins is likely very limited.

• Korean Journal of Chemical Engineering
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• 제35권12호
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• pp.2403-2412
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• 2018

The present study was aimed at evaluating the effect of variable sodium carbonate ($Na_2CO_3$) loading during wet air oxidation (WAO) pretreatment of rice straw in reducing biomass recalcitrance. The research study was intended to increase the cellulose recovery, hemicellulose solubilization, lignin removal in the solid fraction and limiting the generation of inhibitors in the liquid fraction while reducing the chemical input. The operating condition of $169^{\circ}C$, 4 bar, 18 min and 6.5 g/L $Na_2CO_3$ loading resulted in maximum cellulose recovery of 82.07% and hemicellulose solubilization and lignin removal of 85.43% and 65.42%, respectively, with a total phenolic content of 0.36 g/L in the liquid fraction. The crystallinity index increased from 47.69 to 51.25 along with enzymatic digestibility with an increase in $Na_2CO_3$ loading from 0 to 6.5 g/L as a result of removal of barriers for saccharification via effective cleavage of ether and ester bonds cross-linking the carbohydrates and lignin as indicated by FT-IR spectroscopy. A further increase in the $Na_2CO_3$ loading to 9.5 g/L did not significantly increase the sugar release. Thus, it was concluded that 6.5 g/L $Na_2CO_3$ during WAO is sufficient to increase the delignification and deacetylation, leading to significant changes in apparent cellulose crystallinity inter alia improvement in cellulose accessibility and digestibility of rice straw.

• 대한골관절종양학회지
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• 제15권2호
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• pp.111-121
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• 2009

배경: 골육종은 소아 및 청소년기에 가장 흔하게 발생하는 악성 골종양 중 하나이다. 최근 수술적 치료와 항암 화학요법을 병행하여 생존률이 증가하였지만, 아직까지도 항암제는 항암제 내성 및 이차성 악성 종양의 발생 등 여러 문제점을 가지고 있다. 일부 종양은 matrix metalloproteinase(MMPs)의 발현이 증가되어 있고, MMP inhibitor에 대한 연구가 진행되고 있다. 반면 bisphosphonate(BPs) 제제는 골흡수를 억제하는 능력이 있으며, 파골세포와 관계된 골 병변에 광범위하게 사용되고 있다. 또 bisphosphonate 제제는 직접적인 항암효과를 가지고 있는 것으로 알려져 있다. 대상 및 방법: 골육종 세포주(U2OS)를 ibandronate(0, 0.1, 1, 10M)를 이용하여 48시간 동안 처치하였다. 세포의 생존능은 MTT assay를 이용하여, MMP-2와 MT1-MMP의 mRNA level은 reverse-transciption polymerase chain reaction을 이용하여 측정하였으며, MMP-2와 MT1-MMP 단백의 양은 Westernblot을, MMP-2의 활성은 Gelatin zymography를 이용하여 측정하였다. 또, ibandronate 처치 전후의 골육종 세포주의 침습성은 Matrigel invasion assay를 이용하여 측정하였다. 결과: 48시간 ibandronate 처치 후 U2OS 세포주의 침습력은 ibandronate에 대해 용량 의존적으로 감소하였다. 특히 10M 이내의 ibandronate는 세포독성이 나타나지 않았다. 젤라틴 융해능과 MMP-2 및 MT1-MMP의 단백 및 mRNA 정도역시 ibandronate 농도가 증가할수록 감소하였다. 결론: Ibandronate는 골육종 세포주의 MMP-2 및 MT1-MMP의 발현을 억제하였으며, 종양세포의 침습력을 감소시켰다. Bisphosphate의 종양세포 침습 억제 능력은 새로운 전이 억제제의 개발에 도움이 될 것으로 사료된다.

• Korean Chemical Engineering Research
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• 제54권4호
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• pp.494-500
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• 2016

본 연구에서는 백합나무의 아세틸기 제거를 위해 전처리 전에 수산화나트륨을 이용하여 탈아세틸화를 수행하였다. 0.8%의 수산화나트륨을 첨가하여 $60^{\circ}C$에서 80분 동안 반응시켜 헤미셀룰로오스로부터 대부분의 아세틸기를 제거하였다. 탈아세틸화 처리된 바이오매스를 옥살산 전처리에 이용하였으며, 전처리된 바이오매스 투입량(10, 12.5, 15%) 및 효모 투입시간(0, 6, 12, 24시간)에 따라 동시당화발효 및 semi-동시당화발효를 수행하였다. 최대 에탄올 수율은 바이오매스 투입량 10%에서 효모를 당화시작과 동시에 첨가했을 때 120시간 후 26.73 g/L의 에탄올을 생산하였으며 이것은 88.14%의 에탄올 수율에 해당하였다. 바이오매스 투입량 12.5%와 15% 조건에서는 효모 투입시간 6시간 조건에서 각각 32.34 g/L, 27.15 g/L의 에탄올을 생산하였고, 이는 각각 85.58%와 59.87%의 에탄올 수율에 해당하였다. 옥살산 전처리 후 얻어진 액상 가수분해산물로부터 발효저해물질의 제거를 위해 수산화칼슘을 처리하였으며 발효 72시간 후 5.28 g/L의 최대 에탄올을 얻었다.

• 대한후두음성언어의학회지
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• 제19권2호
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• pp.128-132
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• 2008

Background: Laryngeal contact granuloma is an inflammatory hypertrophic granulation tissue arising at around the vocal process of arytenoid cartilage. Various approaches are currently used for the treatment, but a solid guideline has not been established. Objectives: We aimed to compare the each treatment modality in the hope of suggesting a guideline for the successful management of laryngeal contact granuloma. Method: Eighty-seven treatment cases of 56 patients were analyzed. Cases having recent intubation history were excluded from the study. All patients received vocal hygiene education. Proton pump inhibitors (PPI, N = 33) or H2 receptor antagonists ($H_{2}RA$, N =26) were used as a first-line treatment. Among the non-responders to $H_{2}RA$, 11 cases received PPI as a second-line therapy. Eight cases received botulinum toxin injection and 9 cases had laryngomicrosurgical removal. Results: As an initial therapy, response rate to PPI and $H_{2}RA$ was 60.6% and 38.5% respectively, which was not statistically different (p=0.091). Response rate of PPI as the second-line therapy was 36.3% (p=0.162 when compared to that of first-line PPI therapy). Response rate of Botulinum toxin injection was 75%. All cases of surgical removal recurred in a relatively short period (mean 1.9months). Conclusion: In patients having laryngeal contact granuloma, combined therapy with vocal hygiene education and PPI medication would provide more than 60% of therapeutic response. Botulinum toxin injection is highly effective even in non-responders to antireflux therapy. The only indications of surgery are to resolve diagnostic doubt or to treat acute airway compromise.

• 한국미생물·생명공학회지
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• 제40권1호
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• pp.23-29
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• 2012

순천대학교 지의류생물 소재은행(KOLABIC)에서 100종의 지의류 내생 곰팡이를 분양 받아 C. albicans에 대한 항진균 활성을 조사하였다. 고체배지 및 액체배지에 배양시 Usnea rigidula, Parmotrema pseudotinctorum 그리고 Myelochroa sp.가 높은 항진균 활성을 나타내는 물질을 생성함을 알 수 있었다. 이들 3종 지의류 내생 곰팡이의 배양액을 chloroform, ethyl acetate 용매 순으로 추출하고 disc diffusion method를 이용하여 각 추출물의 C. albicans에 대한 항진균 활성도를 측정한 결과 모두 chloroform 추출물에서 높은 활성이 가장 높았으며, 다음으로 ethyl acetate 추출물이 높은 활성을 나타냈다. 항진균성 물질이 기존에 알려진 물질인지에 대한 정보를 알기위해 6 일 동안 배양한 Usnea rigidula와 4일 동안 배양한 Parmotrema pseudotinctorum의 chloroform 추출액에 대하여 HPLC, $C_{18}$ column으로 분리하여 Usnea rigidula (2326)의 6일과 Parmotrema pseudotinctorum (2202)의 4일 배양액에서 각각 2 개의 peak 분획물을 얻었다. 각 분획물을 농축한 후 96 well plate를 이용하여 C. albicans와 C. glabrata에 대한 항진균 활성을 실험한 결과, Parmotrema pseudotinctorum의 주요peak는 control에 비해 항진균 활성이 높게 나타났으며 활성물질은 usnic acid계열의 화합물로 추정되었다.

• 생명과학회지
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• 제28권12호
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• pp.1469-1476
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• 2018

Warburg 효과의 발생은 고형암에서 화학적 항암제의 내성을 발생시킨다. 따라서 호기성 해당과정과 같은 에너지 대사과정은 암 치료의 중요한 표적으로 알려져 있다. Pyruvate dehydrogenase kinase (PDK) 활성 억제물질로 알려진 dichloroacetate (DCA)는 많은 암세포에서 포도당의 호기성 해당과정을 산화적인산화 과정으로 전환시킬 수 있음이 보고되었다. 이 연구는 치료가 매우 어렵다고 알려진 인간 역분화 갑상선 암세포주인 8505C의 성장에 미치는 DCA효과를 조사하였다. DCA는 정상 갑상선 세포주의 성장에는 영향을 주지 않은 반면 8505C 세포주의 성장을 특이적으로 저해하였다. DCA의 처리에 의해 8505C 세포주는 $HIF1{\alpha}$, PDK1, Bcl-2와 같은 항-세포자살 관련 단백질들의 발현이 감소하고, Bax와 p21과 같은 세포자살 유도 단백질과 세포주기 억제 단백질의 증가로 인하여 세포주기 정지와 세포자살 유도에 의해 성장이 억제되었다. 이런 세포의 변화는 DCA 처리에 의한 활성산소족의 생산이 증가하고, 포도당 대사가 호기성 해당과정에서 산화적인산화 과정으로 전환되었기 때문이란 것을 확인하였다. 흥미롭게도, DCA는 포도당 대사과정의 변화뿐만 아니라 sodium/iodine symporter (NIS)의 발현양도 증가시킨다는 것을 확인하였다. 이 연구의 결과로 PDK 활성 저해제는 치료하기 힘든 역분화 갑상선 암 치료제로 이용할 수 있고, 또한 역분화 갑상선 암에 대한 방사능 치료의 효능을 높일 수 있을 것으로 기대된다.