• Archives of Pharmacal Research
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• 제29권4호
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• pp.328-332
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• 2006

The bioequivalence and pharmacokinetics of alendronate sodium tablets were examined by determining the plasma concentration of alendronate. Two groups, consisting of 24 healthy volunteers, each received a 70 mg reference alendronate sodium tablet and a test tablet in a $2{\times}2$ crossover study. There was a 6-day washout period between doses. The plasma alendronate concentration was monitored for 7 h after the dose, using HPLC-Fluorescence Detector (FD). The area under the plasma concentration-time curve from time 0 to the last sampling time at 7 h $(AUC_{0-7h})$ was calculated using the linear-log trapezoidal rule. The maximum plasma drug concentration $(C_{max})$ and the time to reach $C_{max}(T_{max})$ were derived from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed $AUC_{0-7h}\;and\;C_{max}$, and untransformed $T_{max}$. For the test medication versus the reference medication, the $AUC_{0-7h}\;were\;87.63{\pm}29.27\;vs.\;102.44{\pm}69.96ng\;h\;mL^{-1}$ and the $C_{max}$ values were $34.29{\pm}13.77\;vs.\;38.47{\pm}24.39ng\;mL^{-1}$ respectively. The $90\%$ confidence intervals of the mean differences of the logarithmic transformed $AUC_{0-7h}$ and $C_{max}$ values were log 0.8234-log 1.1597 and log 0.8222-log 1.1409, respectively, satisfying the bioequivalence criteria guidelines of both the US Food and Drug Administration and the Korea Food and Drug Administration. The other pharmacokinetic parameters for the test drug versus reference drug, respectively, were: $t_{1/2},\;1.87{\pm}0.62\;vs.\;1.77{\pm}0.54\;h;\;V/F,\;2061.30{\pm}986.49\;vs.\;2576.45{\pm}1826.05\;L;\;CL/F,\;835.32{\pm}357.35\;vs.\;889.48{\pm}485.87\;L\;h^{-1}; K_{el},\;0.42{\pm}0.14\;vs.\;0.40{\pm}0.18\;h^{-1};\;Ka,\;4.46{\pm}3.63\;vs.\;3.80{\pm}3.64\;h^{-1};\;and\;T_{lag},\;0.19{\pm}0.09\;vs.\;0.18{\pm}0.06\;h$. These results indicated that two alendronate formulations(70-mg alendronate sodium) were biologically equivalent and can be prescribed interchangeably.

• 약학회지
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• 제50권4호
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• pp.272-277
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• 2006

This study was undertaken to determine whether the 9 herbal complex induces apoptosis in human breast cancer MCF-7 cells and adriamycin-resistant MCF7/adR cells. Ethanol extracts of Bojungbangamtang (BBTE) and acidic polysaccharide of Red Ginseng (GIN) induced cell death in both MCF-7 and MCF7/adR cells. Ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng also induced $G_2/M$ cell cycle arrest and increased TUNEL positive cells in MCF7/adR cells. In addition, flow cytometric analysis revealed the decreased expression of P-glycoprotein (P-gp) in ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng treated MCF7/adR cells. Similarly, decreased protein levels of P-glycoprotein and multidrug resistance associated proteins-1 were also determined by immunocytometry in ethanol extracts of Bojungbangamtang treated MCF7/adR cells. Taken together these data indicate that ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng inhibit the function of ABC transporters such as multi drug resistance associated proteins (MRPs) and P-glycoprotein as well as induce apoptosis in MCF7/adR cells. Thus, these data suggest that ethanol extracts of Bojungbangamtang and polysaccharide of Red Ginseng can be candidates for the treatment of multidrug-resistant MCF7/adR cells.

• Journal of Applied Biological Chemistry
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• 제64권4호
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• pp.333-341
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• 2021

본 연구는 근권 토양 및 뿌리에 존재하는 근권 미생물 중 미생물 제제로 적합한 균주를 선별하기 위해서 미네랄 가용화능, 10종의 식물 병원성 곰팡이에 대한 항진균 활성 및 식물 생장 촉진 활성을 평가하였다. 결과적으로 불용성 인산, 탄산칼슘, 규소 및 아연 가용화능과 질소고정능, siderophore, indole-3-acetic acid와 aminocyclopropane-1-carboxylate deaminase 생성능 및 7종의 식물 병원성 곰팡이에 대해 항진균 활성을 갖는 DDP346을 선별하였다. 선별된 DDP346은 Acinetobacter pittii DSM21653 (NR_117621.1)와 99.9% 이상의 높은 상동성을 보였으며, 16S rRNA 염기서열을 바탕으로 계통도를 분석한 결과에서도 Acinetobacter pittii와 높은 유연관계를 나타내었다. DDP346의 생장 조건은 온도(10-40 ℃), pH (5-11) 염농도(0-5%) 범위로 확인하였다. 또한 pH 변화와 가용화된 인산 함량 간에 음의 상관계수(r²= -0.913, p <0.01)를 나타내는 것을 확인하였는데, 이는 배양 중에 생성되는 유기산에 의한 것으로 추정된다. 결과적으로 미네랄 가용화능, 식물 병원성 곰팡이에 대한 항진균 활성 및 식물 생장 촉진 활성 평가를 통해 Acinetobacter sp. DDP346을 다목적 미생물 제제로써 활용 가능성을 제시한다.

• Journal of Microbiology and Biotechnology
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• 제31권4호
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• pp.540-549
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• 2021

The Wnt/β-catenin signaling pathway is involved in breast cancer and Myxococcus fulvus KYC4048 is a myxobacterial strain that can produce a variety of bioactive secondary metabolites. Although a previous study revealed that KYC4048 metabolites exhibit anti-proliferative effects on breast cancer, the biochemical mechanism involved in their effects remains unclear. In the present study, KYC4048 metabolites were separated into polar and non-polar (ethyl acetate and n-hexane) fractions via liquid-liquid extraction. The effects of these polar and non-polar KYC4048 metabolites on the viability of breast cancer cells were then determined by MTT assay. Expression levels of Wnt/β-catenin pathway proteins were determined by Western blot analysis. Cell cycle and apoptosis were measured via fluorescence-activated cell sorting (FACS). The results revealed that non-polar KYC4048 metabolites induced cell death of breast cancer cells and decreased expression levels of WNT2B, β-catenin, and Wnt target genes (c-Myc and cyclin D1). Moreover, the n-hexane fraction of non-polar KYC4048 metabolites was found most effective in inducing apoptosis, necrosis, and cell cycle arrest, leading us to conclude that it can induce apoptosis of breast cancer cells through the Wnt/β-catenin pathway. These findings provide evidence that the n-hexane fraction of non-polar KYC4048 metabolites can be developed as a potential therapeutic agent for breast cancer via inhibition of the Wnt/β-catenin pathway.

• Journal of Gastric Cancer
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• 제19권3호
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• pp.301-314
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• 2019

Purpose: Peritoneal carcinomatosis in gastric cancer (GC) patients results in extremely poor prognosis. Malignant ascites samples are the most appropriate biological material to use to evaluate biomarkers for peritoneal carcinomatosis. This study identified exosomal MicroRNAs (miRNAs) differently expressed between benign liver cirrhosis-associated ascites (LC-ascites) and malignant gastric cancer-associated ascites (GC-ascites), and validated their role as diagnostic biomarkers for GC-ascites. Materials and Methods: Total RNA was extracted from exosomes isolated from 165 ascites samples (73 LC-ascites and 92 GC-ascites). Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n=22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were performed to validate the expression levels of selected exosomal miRNAs in the training (n=70) and validation (n=73) cohorts. Furthermore, carcinoembryonic antigen (CEA) levels were determined in ascites samples. Results: The miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly downregulated in the GC-ascites samples compared to the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC]=0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved by the combined analysis of miR-181b-5p and CEA (AUC=0.981 and 0.946 for the training and validation cohorts, respectively). Conclusions: We identified exosomal miRNAs capable of distinguishing between non-malignant and GC-ascites, showing that the combined use of miR-181b-5p and CEA could improve diagnosis.

• 한국미생물·생명공학회지
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• 제47권3호
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• pp.390-400
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• 2019

본 연구에서 부산, 창원, 제주도 일대에서 채취한 토양으로부터 분리한 미생물을 이용하여 식물 생장 촉진활성 및 식물병원성 곰팡이에 대한 길항능을 확인하고자 하였으며, 분리주 간에 비교우위를 통해 Pseudomonas plecoglossicida ANG14, Pseudarthrobacter equi ANG28, Beijerinckia fluminensis ANG34, Acinetobacter calcoaceticus ANG35를 최종 선정하였다. 이들은 ACC deaminase 생성능, IAA 생성능, 질소 고정능, 인산 가용화능 및 siderophore 생성능을 모두 가지며, 일부 식물병원성 곰팡이에 대해 길항능을 가지는 것을 확인하였다. 특히 ANG35의 경우에는 7가지 식물병원성 곰팡이 중 6가지에 대해 비교적 높은 억제율을 나타내어 식물 생장 촉진뿐만 아니라 방제활성을 가지므로 식물이 생장하는 데 도움을 줄 것으로 기대된다. 또한, 4균주 간의 세포외 효소활성 synergy effect를 확인한 결과 단독배양을 했을 때보다 혼합배양 시 세포외 효소활성이 증가하는 것을 확인하였다. 따라서, 식물 생장촉진 활성 및 식물병원성 곰팡이에 대한 결과를 통해 새로운 생물학적 제제로서 이용 가능성을 제시한다.

• Biomolecules & Therapeutics
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• 제29권6호
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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.

• 보건행정학회지
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• 제31권1호
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• pp.114-124
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• 2021

Background: In this study, we aimed to investigate the interaction effects of individual socioeconomic status and regional deprivation on the onset of diabetes complications and diabetes-related hospitalization among type 2 diabetes patients. Methods: Korean National Health Insurance Service National Sample Cohort data from 2002 to 2013 were used. A total of 50,954 patients newly diagnosed with type 2 diabetes from 2004 to 2012 and aged 30 years or above were included. We classified patients into six groups according to individual income level and neighborhood deprivation: 'high in advantaged,' 'high in disadvantaged,' 'middle in advantaged,' 'middle in disadvantaged,' 'low in advantaged,' and 'low in disadvantaged.' We calculated hazard ratios (HR) of onset of diabetes complication and diabetes-related hospitalization using the Cox proportional hazard model, with the reference group as diabetes patients with high income in advantaged regions. Results: In terms of the interaction effects of individual income level and regional socioeconomic level, even with the same low individual income level, the group with a high regional socioeconomic level (low in advantaged) showed low HRs for the onset of diabetes complication (HR, 1.04; 95% confidence interval [CI], 1.00-1.08) compared to the 'low in disadvantaged' group (HR, 1.10; 95% CI, 1.05-1.16). In addition, the 'high in advantaged' group showed slightly higher HRs for the onset of diabetes complication (HR, 1.06; 95% CI, 1.00-1.11) compared to the 'low in advantaged' and it appeared to be associated with slight mitigation of the risk of diabetes complication. For the low-income level, the patients in disadvantaged regions showed the highest HRs for diabetes-related hospitalization (HR, 1.29; 95% CI, 1.19-1.41) compared to the other groups. Conclusion: Although we need to perform further investigations to reveal the mechanisms that led to our results, interaction effects individual socioeconomic status and regional deprivation might be associated with on onset of diabetes complications and diabetes-related hospitalization among type 2 diabetes patients.

• 한국산림과학회지
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• 제110권2호
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• pp.179-188
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• 2021

생물다양성정보학(Biodiversity Informatics)은 정보과학을 생물다양성정보에 접목한 분야로 정이명으로 구성된 학명을 비롯한 종정보를 기초로 일차종발생자료를 구축하고 이를 활용한다. 본 연구에서는 생물다양성 정보의 이용적합도를 기준으로 세계생물다양성정보기구(GBIF)에 출판된 동북아시아 자료의 품질을 BRAHMS 프로그램을 이용하여 평가하고 이를 통해 생물다양성자료 정제의 필요성을 확인하였다. 국립생물자원관, 국립생태원, 국립수목원 등의 국내 생물다양성 관련기관과 더불어 일본, 중국, 대만의 출판 자료는 자료정제과정의 문제로 학명, 지리정보, 채집자, 날짜 등에 대한 오류가 확인된다. 기본적인 속성자료에서 오류가 발생하는 원인은 동아시아의 생물다양성관리기관들이 구조화되지 않은 데이터베이스를 사용하고 평면적인 스프레드시트형 정보를 사용하기 때문이다. 생물다양성 정보 특성상 다양한 정보가 구조화가되지 않을 경우 학명, 인명, 지명, 문헌, 생태정보에 대한 데이터 무결성을 해결하지 못한다. 동아시아 생물다양성정보 관리문제를 극복하기 위해서는 자료의 구조화와 함께 자료정제에 대한 이해도를 높이고, 오류 수정을 위한 지속적인 자료 관리자인 전문 분류학자 양성이 필요하다. 생물다양성 정보관리자는 오류 원인분석을 통해 문서화된 관리 지침을 수정, 추가하는 등 향후 오류 예방을 위한 대책이 필요하며 시스템에 적용시켜야 한다. 이런 모든 과정은 데이터베이스를 기반으로 진행되고 기록되어야 한다. 동아시아의 생물다양성 출판자들은 현재 수준의 단순한 자료구조보다는 생물다양성 정보 관리를 위해 전문적인 선진 프로그램의 사용 혹은 이에 준하는 수준의 고도화된 데이터베이스의 개발이 필요하다.

• 셀메드
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• 제11권4호
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• pp.21.1-21.9
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• 2021

Background: Unani System of Medicine (USM) has its origin to Greece. To ensure and develop the quality, authenticity of Unani drugs, standardization on modern analytical parameter is essential requirement for drugs. Objectives: The aimed of the present study was to develop a standard profile of "Qurṣ-e-Mafasil" by systematic study through authenticated ingredients, pharmacognostic identification followed by physicochemical, TLC, HPTLC fingerprinting analysis as per standard protocol. Material and Methods: In this study three batches of "Qurṣ-e-Mafasil" QM were prepared by standard method as per UPI had been followed by organoleptic properties of formulation such as appearance, color, odor, taste. Powder Microscopy and physicochemical studies were carried out such as Uniformity of weight, Friability, Disintegration time, hardness, LOD, ash vales and extractive values in like aqueous, alcohol & hexane. Further qualitative tests such as Thin-Layer Chromatography (TLC), and High-Performance Thin Layer Chromatography (HPTLC) studies were also carried out to develop fingerprint pattern of the alcoholic solvent extract of QM. Phytochemical screening was carried out in different solvent extracts such as alcoholic, aqueous and chloroform extracts to detect the presence phytoconstituents in the formulation QM. Heavy metals, Microbial Load Contamination and pesticidal residues were also determined. Results: Qurṣ-e-Mafasil showed tablet-like appearance, light brown colour, mild pungent odour and acrid taste. Uniformity of weight (mg), friability (rpm), and hardness (kg/cm) and disintegration time was ranged between (500 to 503), (0.0340 to 0.038), (8.40 to 8.67) and (4-5 minutes) respectively for the three batches. Loss in weight on drying at 105℃ was ranged between (8.3425 to 8.7346). Extracted values were calculated in distilled water ranged between (30.9091 to 31.4358), hexane (1.1419 to 1.4281), and alcohol (3.3352 to 3.3962). The ash values recorded were ranged between (3.7336 to 3.8378), and acid insoluble ash (0.5859 to 0.6112).