• CELLMED
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• v.6 no.4
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• pp.24.1-24.4
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• 2016

The emergence of influenza virus and antigenic drift are potential cause of world-wide pandemic. There are some commercially available drugs in the market to treat influenza. During past decade, however, critical resistances have been raised for biological targets. Because of structural complexity and flexibility of target proteins, applying a computational modeling tool is very beneficial for developing alternative anti-influenza drugs. In this review, we introduced molecular dynamics (MD) simulations approach to reflect full conformational flexibility of proteins during molecular modeling works. Case studies of MD works were summarized for the drug discovery and drug resistance mechanism of anti-influenza pharmaceuticals.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4635-4639
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• 2013

Multi-drug resistance (MDR) is an essential aspect of human lung cancer chemotherapy failure. Recent studies have shown that vinorelbine is involved in underlying processes in human tumors, reversing the MDR inseveral types of cancer cells. However, the roles and potential mechanism are not fully clear. In this study, we explored effects of vinorelbine in multi-drug resistance reversal of human lung cancer A549/DDP cells. We found that vinorelbine increased drug sensitivity to cisplatin and intracellular accumulation of rhodamine-123, while decreasing expression of P-glycoprotein (P-gp), multi-drug resistance-associated protein (MRP1) and glutathione-S-transferase ${\pi}$ (GST-${\pi}$) in A549/DDP cells. At the same time, we also established downregulation of p-Akt and decreased transcriptional activation of NF-${\kappa}B$ and twist after vinorelbine treatment. The results indicated that vinorelbine might be used as a potential therapeutic strategy in human lung cancer.

• Journal of Ginseng Research
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• v.31 no.2
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• pp.74-78
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• 2007

Multi-drug resistance (MDR) is a major problem in cancer chemotherapy and has often ended up with termination of the therapy. The aim of this study was to identify any fractions of Korean red ginseng that would be effective in modulating for MDR. Although ginsenosides have been reviewed as possible MDR modulators, the MDR modulation activity of the other component is unknown. Therefore, a red ginseng was extracted with methanol, ether, ethylacetate, and n-butanol, followed by several fractionations by silica gel chromatography. And the activity of MDR modulating for these fractions was examined via sulforrhodamine B assay. We have found that several ether fractions, as nonsaponin components are effective on MDR modulation. We have expect that these results helpful to improvement of cancer chemotherapy.

• Tuberculosis and Respiratory Diseases
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• v.75 no.5
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• pp.188-198
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• 2013

Over the past decade, several kinase inhibitors have been approved based on their clinical benefit in cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. To date, several major mechanisms of acquired resistance, such as secondary mutation of the epidermal growth factor receptor (EGFR) gene, amplification of the MET gene and overexpression of hepatocyte growth factor, have been reported. This review describes the recent findings on the mechanisms of primary and acquired resistance to EGFR tyrosine kinase inhibitors and acquired resistance to anaplastic lymphoma kinase inhibitors, primarily focusing on non-small cell lung carcinoma.

• Journal of Pharmaceutical Investigation
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• v.20 no.4
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• pp.179-191
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• 1990

A central dogma of pharmacology is that only unbound drug is capable of translocation across biological membrane. Thus, hepatic uptake is assumed to be solely determined by the unbound concentration of the diffusible moiety at the surface of the liver cell. However, an increasing number of experimental observations with xenobiotics that are normally very extensively bound to plasma proteins (>99%) appear to be inconsistent with these assumptions. This suggested that in addition to progressive spontaneous dissociation within the liver sinusoids and space of Disse, direct interactions of the albumin-drug complex at the plasma membrane may facilitate dissociation of the complex. To explain this phenomena. called albumin-mediated uptake, 4 mechanisms have been suggested. The validity of such hypotheses needs to be examined by the further study. Because albumin-mediated uptake has also been observed to occur in other plasma proteins, protein-mediated uptake rather than albumin-mediated uptake seems to be acceptable.

• Journal of Integrative Natural Science
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• v.6 no.4
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• pp.205-210
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• 2013

Human P-gp is a protein responsible for the multidrug resistance (MDR) and causes failure of cancer chemotherapy. Till date no X-ray crystal structure is reported for this membrane protein, which hampers active research in the field. We performed homology modeling to develop three dimensional (3D) model of P-gp, and docking studies of the verapamil and curcumin have been performed to gain insight into the interaction mechanism between inhibitors and P-gp. It was identified that the inhibitors docked into the upper part of P-gp and interacted through the hydrophobic interactions.

• Journal of Microbiology and Biotechnology
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• v.22 no.8
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• pp.1107-1112
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• 2012

Outbreaks of foodborne diseases associated with Vibrio species such as V. parahaemolyticus, V. vulnificus, and V. cholerae frequently occur in countries having a dietary habit of raw seafood consumption. For rapid identification of different Vibrio species involved in foodborne diseases, whole-cell protein pattern analysis for 13 type strains of 12 Vibrio species was performed using SDS-PAGE analysis. Pathogenic Vibrio species such as V. parahaemolyticus, V. vulnificus, V. cholerae, V. alginolyticus, V. fluvialis, and V. mimicus were included in the 12 Vibrio species used in this study. Each of the 12 Vibrio species showed clearly specific band patterns of its own. Two different strains of V. parahaemolyticus showed two different SDS-PAGE whole-cell protein patterns, giving the possibility of categorizing isolated strains in the same V. parahaemolyticus species into two subgroups. The 36 Vibrio isolates collected from sushi restaurants in Busan were all identified as V. parahaemolyticus by comparing their protein patterns with those of Vibrio type strains. The identified isolates were categorized into two different subgroups of V. parahaemolyticus. The whole-cell protein pattern analysis by SDS-PAGE can be used as a specific, rapid, and simple identification method for Vibrio spp. involved in foodborne diseases at the subspecies level.

• Journal of Dairy Science and Biotechnology
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• v.23 no.2
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• pp.115-123
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• 2005

Microcapsules consisting of natural, biodegradable polymers for controlled and/or sustained core release applications are needed. Physicochemical properties of whey proteins suggest that they may be suitable wall materials in developing such microcapsules. The objectives of the research were to develop water-insoluble, whey protein-based microcapsules containing a model water-soluble drug using a chemical cross-linking agent, glutaraldehyde, and to investigate core release from these capsules at simulated physiological conditions. A model water soluble drug, theophylline, was suspended in whey protein isolate (WPI) solution. The suspension was dispersed in a mixture of dichloromethane and hexane containing 1% biomedical polyurethane. Protein matrices were cross-linked with 7.5-30 ml of glutaraldehyde-saturated toluene (GAST) for 1-3 hr. Microcapsules were harvested, washed, dried and analyzed for core retention, microstructure, and core release in enzyme-free simulated gastric fluid (SGF) and simulated intestinal fluid(SIF) at $37^{\circ}C$. A method consisting of double emulsification and heat gelation was also developed to prepare water-insoluble, whey protein-based microcapsules containing anhydrous milkfat (AMF) as a model apolar core. AMF was emulsified into WPI solution (15${\sim}$30%, pH 4.5-7.2) at a proportion of 25${\sim}$50%(w/w, on dry basis). The oil-in-water emulsion was then added and dispersed into corn oil ($50^{\circ}C$) to form an O/W/O double emulsion and then heated at $85^{\circ}C$ for 20 min for gelation of whey protein wall matrix. Effects of emulsion composition and pH on core retention, microstructure, and water-solubility of microcapsules were determined. Overall results suggest that whey proteins can be used in developing microcapsules for controlled and sustained core release applications.

• Journal of Ginseng Research
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• v.44 no.5
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• pp.680-689
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• 2020

Background: Peptides have diverse and important physiological roles in plants and are ideal markers for species identification. It is unclear whether there are specific peptides in Panax quinquefolius L. (PQ). The aims of this study were to identify Quinetides, a series of diverse posttranslational modified native peptides of the ribonuclease-like storage protein (ginseng major protein), from PQ to explore novel peptide markers and develop a new method to distinguish PQ from Panax ginseng. Methods: We used different fragmentation modes in the LTQ Orbitrap analysis to identify the enriched Quinetide targets of PQ, and we discovered Quinetide markers of PQ and P. ginseng using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis. These "peptide markers" were validated by simultaneously monitoring Rf and F11 as standard ginsenosides. Results: We discovered 100 Quinetides of PQ with various post-translational modifications (PTMs), including a series of glycopeptides, all of which originated from the protein ginseng major protein. We effectively distinguished PQ from P. ginseng using new "peptide markers." Four unique peptides (Quinetides TP6 and TP7 as markers of PQ and Quinetides TP8 and TP9 as markers of P. ginseng) and their associated glycosylation products were discovered in PQ and P. ginseng. Conclusion: We provide specific information on PQ peptides and propose the clinical application of peptide markers to distinguish PQ from P. ginseng.

• Archives of Pharmacal Research
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• v.12 no.3
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• pp.160-165
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• 1989

Binding of sulfaethidole to bovine serum albumin was studied by equilibrium dialysis, fluorescence probe technique, uv difference spectrophotometry and circular dichroism. Equilibrium dialysis method enabled us to estimate the total number of drug binding sites of albumin molecule. For sulfaethidole, albumin had 6 primary and 40 secondary binding sites. The primary and secondary binding constants were 0.9 * 10/sup 5/ M/sup -1/ and 0.2 * 10/sup 6/ M/sup -1/, respectivitely. 1-Anilino-8-naphthalenesulfonate (ANS) and 2-(4-hydroxylbenzeneazo)- benzoic acid (HBAB) were used as the fluorescence probe and the uv spectrophotometric probe, respectively. In fluorescence probe technique, results indicated that the number of higher affinity drug binding site of albumin was 1 and the number of lower affinity drug binding sites of albumin was 3, and the primary and secondary drug binding constants for bovine serum albumin were 2.15 * 10/sup 5/M/sup -1/ and 1.04 * 10/sup 5/ M/sup -1/, respectively. In uv difference spectrophotometry, binding sites were 3 and binding constant was 1.88 * 10/sup 5/M/sup -1/. The above spectrophotometry, binding sites were 3 and binding constant was 1.88 * 10/sup 5/M/sup -1/. The above results suggest that several different methods should be used in ompensation for insufficient information about drug binding to albumin molecule given by only one method.