• Title/Summary/Keyword: New drug development

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Antimicrobial-resistant Bacteria: An Unrecognized Work-related Risk in Food Animal Production

  • Neyra, Ricardo Castillo;Vegosen, Leora;Davis, Meghan F.;Price, Lance;Silbergeld, Ellen K.
    • Safety and Health at Work
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    • v.3 no.2
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    • pp.85-91
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    • 2012
  • The occupations involved in food animal production have long been recognized to carry significant health risks for workers, with special attention to injuries. However, risk of pathogen exposure in these occupations has been less extensively considered. Pathogens are a food safety issue and are known to be present throughout the food animal production chain. Workers employed at farms and slaughterhouses are at risk of pathogen exposure and bacterial infections. The industrialization of animal farming and the use of antimicrobials in animal feed to promote growth have increased the development of antimicrobial resistance. The changed nature of these pathogens exposes workers in this industry to new strains, thus modifying the risks and health consequences for these workers. These risks are not yet recognized by any work-related health and safety agency in the world.

SH2D4A regulates cell proliferation via the ERα/PLC-γ/PKC pathway

  • Li, Tingting;Li, Wei;Lu, Jingyu;Liu, Hong;Li, Yinghui;Zhao, Yanyan
    • BMB Reports
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    • v.42 no.8
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    • pp.516-522
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    • 2009
  • SH2D4A, comprising a single SH2 domain, is a novel protein of the SH2 signaling protein family. We have previously demonstrated SH2D4A is expressed ubiquitously in various tissues and is located in the cytoplasm. In this study we investigated the function of SH2D4A in human embryonic kidney (HEK) 293 cells using interaction analysis, cell proliferation assays, and kinase activity detection. SH2D4A was found to directly bind to estrogen receptor $\alpha$ (ER$\alpha$), and prevent the recruitment of phospholipase C-$\gamma$ (PLC-$\gamma$) to ER$\alpha$. Moreover, we observed its inhibitory effects on estrogen-induced cell proliferation, involving the protein kinase C (PKC) signaling pathway. Together, these findings suggested that SH2D4A inhibited cell proliferation by suppression of the ER$\alpha$/PLC-$\gamma$/PKC signaling pathway. SH2D4A may be useful for the development of a new anti-cancer drug acting as an ER signaling modulator.

Multivesicular Liposomes for Oral Delivery of Recombinant Human Epidermal Growth Factor

  • Li Hong;An Jun Hee;Park Jeong-Sook;Han Kun
    • Archives of Pharmacal Research
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    • v.28 no.8
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    • pp.988-994
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    • 2005
  • The purpose of the present study was to prepare multivesicular liposomes with a high drug loading capacity and to investigate its potential applicability in the oral delivery of a peptide, human epidermal growth factor (rhEGF). The multivesicular liposomes containing rhEGF was prepared by a two-step water-in-oil-in-water double emulsification process. The loading efficiency was increased as rhEGF concentration increased from 1 to 5mg/mL, reaching approximately $60\%$ at 5 mg/mL. Approximately $47\%$ and $35\%$ of rhEGF was released from the multivesicular liposomes within 6 h in simulated intra-gastric fluid (pH 1.2) and intra-intestinal fluid (pH 7.4), respectively. rhEGF-loaded multivesicular liposomes markedly suppressed the enzymatic degradation of the peptide in an incubation with the Caco-2 cell homogenate. However, the transport of rhEGF from the multivesicular liposomes to the basolateral side of Caco­2 cells was two times lower than that of the rhEGF in aqueous solution. The gastric ulcer healing effect of rhEGF-loaded multivesicular liposomes was significantly enhanced compared with that of rhEGF in aqueous solution; the healing effect of the liposomes was comparable to that of the cimetidine in rats. Collectively, these results indicate that rhEGF-loaded multivesicular liposomes may be used as a new strategy for the development of an oral delivery system in the treatment of peptic ulcer diseases.

Analysis and Subclass Classification of Microarray Gene Expression Data Using Computational Biology (전산생물학을 이용한 마이크로어레이의 유전자 발현 데이터 분석 및 유형 분류 기법)

  • Yoo, Chang-Kyoo;Lee, Min-Young;Kim, Young-Hwang;Lee, In-Beum
    • Journal of Institute of Control, Robotics and Systems
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    • v.11 no.10
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    • pp.830-836
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    • 2005
  • Application of microarray technologies which monitor simultaneously the expression pattern of thousands of individual genes in different biological systems results in a tremendous increase of the amount of available gene expression data and have provided new insights into gene expression during drug development, within disease processes, and across species. There is a great need of data mining methods allowing straightforward interpretation, visualization and analysis of the relevant information contained in gene expression profiles. Specially, classifying biological samples into known classes or phenotypes is an important practical application for microarray gene expression profiles. Gene expression profiles obtained from tissue samples of patients thus allowcancer classification. In this research, molecular classification of microarray gene expression data is applied for multi-class cancer using computational biology such gene selection, principal component analysis and fuzzy clustering. The proposed method was applied to microarray data from leukemia patients; specifically, it was used to interpret the gene expression pattern and analyze the leukemia subtype whose expression profiles correlated with four cases of acute leukemia gene expression. A basic understanding of the microarray data analysis is also introduced.

Monohydrated Sulfuric and Phosphoric Acids with Different Hydrogen Atom Orientations: DFT and Ab initio Study

  • Kolaski, Maciej;Cho, Seung-Joo
    • Bulletin of the Korean Chemical Society
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    • v.33 no.6
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    • pp.1998-2004
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    • 2012
  • We carried out DFT calculations for monohydrated sulfuric and phosphoric acids. We are interested in clusters which differ in orientation of hydrogen atoms only. Such molecular complexes are close in energy, since they lie in the vicinity of the global minimum energy structure on the flat potential energy surface. For monohydrated sulfuric acid we identified four different isomers. The monohydrated phosphoric acid forms five different conformers. These systems are difficult to study from the theoretical point of view, since binding energy differences in several cases are very small. For each structure, we calculated harmonic vibrational frequencies to be sure that if the optimized structures are at the local or global minima on the potential energy surface. The analysis of calculated -OH vibrational frequencies is useful in interpretation of infrared photodissociation spectroscopy experiments. We employed four different DFT functionals in our calculations. For each structure, we calculated binding energies, thermodynamic properties, and harmonic vibrational frequencies. Our analysis clearly shows that DFT approach is suitable for studying monohydrated inorganic acids with different hydrogen atom orientations. We carried out MP2 calculations with aug-cc-pVDZ basis set for both monohydrated acids. MP2 results serve as a benchmark for DFT calculations.

Optimal Extraction Condition and Characterization of Antidementia Acetylcholinesterase Inhibitor from Job's Tears (Coix lachrymajobi L.) (율무로부터 항치매성 Acetylcholinesterase 저해물질의 최적추출 조건 및 특성)

  • Seo, Dong-Soo;Jang, Jeong-Hoon;Kim, Na-Mi;Lee, Jong-Soo
    • Korean Journal of Medicinal Crop Science
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    • v.17 no.6
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    • pp.434-438
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    • 2009
  • For the development of a new antidementia functional food or alternative drug using agricultural products, Job's tears (Coix lachrymajobi L.), which shows high acetylcholinesterase (AChE) inhibitory activity (55.1%) was selected and the extraction conditions of AChE inhibitor were optimized. AChE inhibitor of Job's tears was maximally extracted when it was treated with 60% methanol at $40^{\circ}C$ for 6 h. The AChE inhibitor of the methanol extracts was partially purified by systematic solvent extraction, thin layer chromatography, silica gel chromatography and reverse-phase HPLC and the partial purified AChE inhibitor with inhibitory activity ($IC_{50}$) of $0.608\;{\mu}g$ was obtained. The partial purified AChE inhibitor was soluble in methanol and hexane, and insoluble in water. Its maximum absorption spectra was 230 nm and also it was stable in the range of $30^{\circ}C$ and $70^{\circ}C$ and pH 4.0-8.0 for 1 h.

Novel biological strategies to enhance the radiation therapeutic ratio

  • Kim, Jae Ho;Jenrow, Kenneth A.;Brown, Stephen L.
    • Radiation Oncology Journal
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    • v.36 no.3
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    • pp.172-181
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    • 2018
  • Successful anticancer strategies require a differential response between tumor and normal tissue (i.e., a therapeutic ratio). In fact, improving the effectiveness of a cancer therapeutic is of no clinical value in the absence of a significant increase in the differential response between tumor and normal tissue. Although radiation dose escalation with the use of intensity modulated radiation therapy has permitted the maximum tolerable dose for most locally advanced cancers, improvements in tumor control without damaging normal adjacent tissues are needed. As a means of increasing the therapeutic ratio, several new approaches are under development. Drugs targeting signal transduction pathways in cancer progression and more recently, immunotherapeutics targeting specific immune cell subsets have entered the clinic with promising early results. Radiobiological research is underway to address pressing questions as to the dose per fraction, irradiated tumor volume and time sequence of the drug administration. To exploit these exciting novel strategies, a better understanding is needed of the cellular and molecular pathways responsible for both cancer and normal tissue and organ response, including the role of radiation-induced accelerated senescence. This review will highlight the current understanding of promising biologically targeted therapies to enhance the radiation therapeutic ratio.

A preliminary study of semi-quantitative, comparative evaluation of split or half fingerprints using Densitometric Image Analysis (DIA) - Inter-analyst differences for split or half fingerprints -

  • Song, Minkyu;Kim, Seung-chan;Choi, Sung-Woon
    • Analytical Science and Technology
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    • v.34 no.2
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    • pp.56-67
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    • 2021
  • Due to the difficulty of grading visualized fingerprints with previously known evaluation methods for the comparison of split fingerprints, a preliminary study was performed with the densitometric image analysis (DIA) method as a potential quantitative and supplementary evaluation method. Each image of inked split fingerprints was divided into 4 zones for analysis. Weekly intra- and inter- analysis by two analysts with three whole fingerprints that were constructed by combining inked split fingerprints showed that the average area values and the ranges of difference fluctuation were not significantly different between strong fingerprints and strong-weak pairs, while they were different in weak fingerprints and weak-weak pairs. In the case of weak fingerprints, the exact acquisition of ridges was difficult and this seemed to influence the results. An additional study is needed for the improved reliability using DIA method with weak fingerprints such as 8 zones division rather than 4 zones. In addition, the analysis results performed by several analysts at different times should be used to improve the reliability of the analysis method further. Based on the above result, it can be judged that utilizing the DIA method as a secondary evaluation method of the existing scoring system would be effective with the additional studies especially on weak fingerprints.

A Convenient Manufacturing Method for Mass Production of EGCG Rich Green Tea Extract (Epigallocatechin Gallate 고함유 녹차추출물의 제조공정 개선)

  • Seo, Eun Hye;Kim, Eun Jeong;Cheon, Seong Bong;Yoon, Min Ji;Choi, Sang Un;Ryu, Geon-Seek;Ryu, Shi Yong
    • Korean Journal of Pharmacognosy
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    • v.50 no.3
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    • pp.198-204
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    • 2019
  • A facile and convenient method was developed for the mass production of epigallocatechin gallate (EGCG) rich green tea extract (Er-GTE). The Er-GTE was successfully obtained from the crude water extract of green tea by the combination of two step purification, i.e., a simple adsorption process on the cation exchange resins (Trilite SCR-B) followed by the chromatography with Diaion HP-20 resins. The green tea extract produced by water extraction under $45^{\circ}C$ was subjected to adsorb on the strongly acidic cation exchange resin, Trilite SCR-B. The eluate passed through the resin was reabsorbed on Diaion HP-20 resin, which was subjected to elute with a mixture of water and alcohol by conventional chromatographical manner. The EGCG content in Er-GTE was estimated above 97% by HP-LC analysis and the newly developed method was regarded as the most suitable and appropriate process for the mass production of epigallocatechin gallate rich green tea extract (Er-GTE).

Differential Sensitivity of Wild-Type and BRAF-Mutated Cells to Combined BRAF and Autophagy Inhibition

  • Yeom, Hojin;Hwang, Sung-Hee;Han, Byeal-I;Lee, Michael
    • Biomolecules & Therapeutics
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    • v.29 no.4
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    • pp.434-444
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    • 2021
  • BRAF inhibitors are insufficient monotherapies for BRAF-mutated cancer; therefore, we investigated which inhibitory pathway would yield the most effective therapeutic approach when targeted in combination with BRAF inhibition. The oncogenic BRAF inhibitor, PLX4720, increased basal autophagic flux in BRAF-mutated cells compared to wild-type (WT) BRAF cells. Interestingly, early autophagy inhibition improved the effectiveness of PLX4720 regardless of BRAF mutation, whereas late autophagy inhibition did not. Although ATG5 knockout led to PLX4720 resistance in both WT and BRAF-mutated cells, the MEK inhibitor trametinib exhibited a synergistic effect on PLX4720 sensitivity in WT BRAF cells but not in BRAF-mutated cells. Conversely, the prolonged inhibition of endoplasmic reticulum (ER) stress reduced basal autophagy in BRAF-mutated cells, thereby increasing PLX4720 sensitivity. Taken together, our results suggest that the combined inhibition of ER stress and BRAF may simultaneously suppress both pro-survival ER stress and autophagy, and may therefore be suitable for treatment of BRAF-mutated tumors whose autophagy is increased by chronic ER stress. Similarly, for WT BRAF tumors, therapies targeting MEK signaling may be a more effective treatment strategy. Together, this study presents a rational combination treatment strategy to improve the efficacy of BRAF inhibitors depending on BRAF mutation status.