196 results on '"Eun J"'
Search Results
2. Development of a Mature B Lymphocyte Probe through Gating-Oriented Live-Cell Distinction (GOLD) and Selective Imaging of Topical Spleen
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Heewon Cho, Haw-Young Kwon, Youngsook Kim, Kyungwon Kim, Eun Jig Lee, Nam-Young Kang, and Young-Tae Chang
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Chemistry ,QD1-999 - Published
- 2024
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3. Exploring the sedative properties of natural molecules from hop cones (Humulus lupulus) as promising natural anxiolytics through GABA receptors and the human serotonin transporter
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Amany Belal, Mohammed S. Elballal, Ahmed A. Al-Karmalawy, Ahmed H. E. Hassan, Eun Joo Roh, Mohammed M. Ghoneim, Mohamed A. M. Ali, Ahmad J. Obaidullah, Jawaher M. Alotaibi, Salwa Shaaban, and Mohamed A. Elanany
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natural molecules ,hop cones ,natural anxiolytics ,DFT ,molecular dynamics ,RMSF analysis ,Chemistry ,QD1-999 - Abstract
This research work aimed to identify the main components that are responsible for the sedative properties of hop cones and allocate their targets. This investigation was performed through molecular docking, molecular dynamic simulations, root mean square fluctuation (RMSF) analysis, and DFT calculation techniques. The tested compounds from Humulus lupulus were compared to diazepam and paroxetine. Molecular docking showed that two-thirds of the compounds had a good affinity to gamma-aminobutyric acid (GABA), outperforming diazepam, while only three surpassed paroxetine on the SERT. Compounds 3,5-dihydroxy-4,6,6-tris(3-methylbut-2-en-1-yl)-2-(3-methylbutanoyl)cyclohexa-2,4-dien-1-one (5) and (S,E)-8-(3,7-dimethylocta-2,6-dien-1-yl)-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one (15) showed stable binding and favorable energy parameters, indicating their potential for targeting GABA receptors and the SERT. This study provides a basis for future clinical research on these promising compounds.
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- 2024
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4. Nickel oxide electroplating and electrode surface modification for electrochemical detection of glutamate
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Eun Joong Kim, Chung Mu Kang, and Ji-Hyung Han
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Nickel Oxide ,Electroplating ,Electrode surface modification ,Electrochemical activation ,APTES immobilization ,Electrochemical glutamate sensing ,Industrial electrochemistry ,TP250-261 ,Chemistry ,QD1-999 - Abstract
The electrochemical behavior and catalytic properties of nickel oxide (NiOx) are enhanced through cathodic electroplating and subsequent electrochemical activation in an alkaline aqueous electrolyte. The electrochemical detection of ʟ-glutamate becomes feasible by introducing an amine group through immobilizing APTES ((3-aminopropyl)triethoxysilane) on the NiOx surface, resulting in a positive charge. The synergistic effect of electrochemically activated electroplated NiOx and the APTES-modified surface facilitates the effective electrochemical detection of trace ʟ-glutamate. The APTES-activated NiOx electrode exhibits a linear detection range of 0.2 nM to 2 mM for glutamate. This relatively wide concentration range is promising for the analysis of human biological fluids.
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- 2024
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5. Role of GO and Photoinitiator Concentration on Curing Behavior of PEG-Based Polymer for DLP 3D Printing
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Men Thi Hong Nguyen, Jong Hoon Kim, Woo Tae Jang, Yun Jae Jung, Eun Jin Park, Tai Hwan Ha, Sang Jung Ahn, and Young Heon Kim
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Chemistry ,QD1-999 - Published
- 2024
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6. Enhanced Preservation of Climacteric Fruit with a Cellulose Nanofiber-Based Film Coating
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Hojung Kwak, Joonggon Kim, Eun Jin Lee, and Jinho Hyun
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Chemistry ,QD1-999 - Published
- 2023
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7. Syndecan-1 Plays a Role in the Pathogenesis of Sjögren’s Disease by Inducing B-Cell Chemotaxis through CXCL13–Heparan Sulfate Interaction
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Nan Young Lee, Hirut Yadeta Ture, Eun Ju Lee, Ji Ae Jang, Gunwoo Kim, and Eon Jeong Nam
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Sjögren’s disease ,syndecan-1 ,epithelial cell ,CXCL13 ,B cell ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
In Sjögren’s disease (SjD), the salivary glandular epithelial cells can induce the chemotaxis of B cells by secreting B-cell chemokines such as C-X-C motif chemokine ligand 13 (CXCL13). Syndecan-1 (SDC-1) is a major transmembrane heparan sulfate proteoglycan (HSPG) predominantly expressed on epithelial cells that binds to and regulates heparan sulfate (HS)-binding molecules, including chemokines. We aimed to determine whether SDC-1 plays a role in the pathogenesis of SjD by acting on the binding of HS to B-cell chemokines. To assess changes in glandular inflammation and SDC-1 concentrations in the submandibular gland (SMG) and blood, female NOD/ShiLtJ and sex- and age-matched C57BL/10 mice were used. In the SMG of NOD/ShiLtJ mice, inflammatory responses were identified at 8 weeks of age, but increased SDC-1 concentrations in the SMG and blood were observed at 6 weeks of age, when inflammation had not yet started. As the inflammation of the SMG worsened, the SDC-1 concentrations in the SMG and blood increased. The expression of the CXCL13 and its receptor C-X-C chemokine receptor type 5 (CXCR5) began to increase in the SMG at 6 weeks of age and continued until 12 weeks of age. Immunofluorescence staining in SMG tissue and normal murine mammary gland cells confirmed the co-localization of SDC-1 and CXCL13, and SDC-1 formed a complex with CXCL13 in an immunoprecipitation assay. Furthermore, NOD/ShiLtJ mice were treated with 5 mg/kg HS intraperitoneally thrice per week for 6–10 weeks of age, and the therapeutic effects in the SMG were assessed at the end of 10 weeks of age. NOD/ShiLtJ mice treated with HS showed attenuated salivary gland inflammation with reduced B-cell infiltration, germinal center formation and CXCR5 expression. These findings suggest that SDC-1 plays a pivotal role in the pathogenesis of SjD by binding to CXCL13 through the HS chain.
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- 2024
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8. Evolution and Competitive Struggles of Lactiplantibacillus plantarum under Different Oxygen Contents
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Sojeong Heo, Eun Jin Jung, Mi-Kyung Park, Moon-Hee Sung, and Do-Won Jeong
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Lactiplantibacillus plantarum ,pan-genome ,core-genome ,nitrate metabolism ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Lactiplantibacillus (Lb.) plantarum is known as a benign bacterium found in various habitats, including the intestines of animals and fermented foods. Since animal intestines lack oxygen, while fermented foods provide a limited or more oxygen environment, this study aimed to investigate whether there were genetic differences in the growth of Lb. plantarum under aerobic vs. anaerobic conditions. Genomic analysis of Lb. plantarum obtained from five sources—animals, dairy products, fermented meat, fermented vegetables, and humans—was conducted. The analysis included not only an examination of oxygen-utilizing genes but also a comparative pan-genomic analysis to investigate evolutionary relationships between genomes. The ancestral gene analysis of the evolutionary pathway classified Lb. plantarum into groups A and B, with group A further subdivided into A1 and A2. It was confirmed that group A1 does not possess the narGHIJ operon, which is necessary for energy production under limited oxygen conditions. Additionally, it was found that group A1 has experienced more gene acquisition and loss compared to groups A2 and B. Despite an initial assumption that there would be genetic distinctions based on the origin (aerobic or anaerobic conditions), it was observed that such differentiation could not be attributed to the origin. However, the evolutionary process indicated that the loss of genes related to nitrate metabolism was essential in anaerobic or limited oxygen conditions, contrary to the initial hypothesis.
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- 2024
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9. Pyroptosis in Skeleton Diseases: A Potential Therapeutic Target Based on Inflammatory Cell Death
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Qian Wu, Jiacheng Du, Eun Ju Bae, and Yunjung Choi
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pyroptosis ,inflammation ,skeleton diseases ,treatment ,cell death ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Skeletal disorders, including fractures, osteoporosis, osteoarthritis, rheumatoid arthritis, and spinal degenerative conditions, along with associated spinal cord injuries, significantly impair daily life and impose a substantial burden. Many of these conditions are notably linked to inflammation, with some classified as inflammatory diseases. Pyroptosis, a newly recognized form of inflammatory cell death, is primarily triggered by inflammasomes and executed by caspases, leading to inflammation and cell death through gasdermin proteins. Emerging research underscores the pivotal role of pyroptosis in skeletal disorders. This review explores the pyroptosis signaling pathways and their involvement in skeletal diseases, the modulation of pyroptosis by other signals in these conditions, and the current evidence supporting the therapeutic potential of targeting pyroptosis in treating skeletal disorders, aiming to offer novel insights for their management.
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- 2024
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10. Epigenetics of Skeletal Muscle Atrophy
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Jiacheng Du, Qian Wu, and Eun Ju Bae
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skeletal muscle atrophy ,epigenetics ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Skeletal muscle atrophy, characterized by diminished muscle strength and mass, arises from various causes, including malnutrition, aging, nerve damage, and disease-related secondary atrophy. Aging markedly escalates the prevalence of sarcopenia. Concurrently, the incidence of muscle atrophy significantly rises among patients with chronic ailments such as heart failure, diabetes, and chronic obstructive pulmonary disease (COPD). Epigenetics plays a pivotal role in skeletal muscle atrophy. Aging elevates methylation levels in the promoter regions of specific genes within muscle tissues. This aberrant methylation is similarly observed in conditions like diabetes, neurological disorders, and cardiovascular diseases. This study aims to explore the relationship between epigenetics and skeletal muscle atrophy, thereby enhancing the understanding of its pathogenesis and uncovering novel therapeutic strategies.
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- 2024
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11. A Comparative Analysis of Two Automated Quantification Methods for Regional Cerebral Amyloid Retention: PET-Only and PET-and-MRI-Based Methods
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Sunghwan Kim, Sheng-Min Wang, Dong Woo Kang, Yoo Hyun Um, Eun Ji Han, Sonya Youngju Park, Seunggyun Ha, Yeong Sim Choe, Hye Weon Kim, Regina EY Kim, Donghyeon Kim, Chang Uk Lee, and Hyun Kook Lim
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amyloid retention ,automated quantification ,PET-and-MRI-based method ,Alzheimer’s disease ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Accurate quantification of amyloid positron emission tomography (PET) is essential for early detection of and intervention in Alzheimer’s disease (AD) but there is still a lack of studies comparing the performance of various automated methods. This study compared the PET-only method and PET-and-MRI-based method with a pre-trained deep learning segmentation model. A large sample of 1180 participants in the Catholic Aging Brain Imaging (CABI) database was analyzed to calculate the regional standardized uptake value ratio (SUVR) using both methods. The logistic regression models were employed to assess the discriminability of amyloid-positive and negative groups through 10-fold cross-validation and area under the receiver operating characteristics (AUROC) metrics. The two methods showed a high correlation in calculating SUVRs but the PET-MRI method, incorporating MRI data for anatomical accuracy, demonstrated superior performance in predicting amyloid-positivity. The parietal, frontal, and cingulate importantly contributed to the prediction. The PET-MRI method with a pre-trained deep learning model approach provides an efficient and precise method for earlier diagnosis and intervention in the AD continuum.
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- 2024
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12. Advancing Cardiovascular Drug Screening Using Human Pluripotent Stem Cell-Derived Cardiomyocytes
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Jisun Oh, Oh-Bin Kwon, Sang-Wook Park, Jun-Woo Kim, Heejin Lee, Young-Kyu Kim, Eun Ji Choi, Haiyoung Jung, Dong Kyu Choi, Bae Jun Oh, and Sang-Hyun Min
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human pluripotent stem cells ,cardiomyocytes ,drug screening ,cardiovascular pharmacology ,high-throughput assays ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as a promising tool for studying cardiac physiology and drug responses. However, their use is largely limited by an immature phenotype and lack of high-throughput analytical methodology. In this study, we developed a high-throughput testing platform utilizing hPSC-CMs to assess the cardiotoxicity and effectiveness of drugs. Following an optimized differentiation and maturation protocol, hPSC-CMs exhibited mature CM morphology, phenotype, and functionality, making them suitable for drug testing applications. We monitored intracellular calcium dynamics using calcium imaging techniques to measure spontaneous calcium oscillations in hPSC-CMs in the presence or absence of test compounds. For the cardiotoxicity test, hPSC-CMs were treated with various compounds, and calcium flux was measured to evaluate their effects on calcium dynamics. We found that cardiotoxic drugs withdrawn due to adverse drug reactions, including encainide, mibefradil, and cetirizine, exhibited toxicity in hPSC-CMs but not in HEK293-hERG cells. Additionally, in the effectiveness test, hPSC-CMs were exposed to ATX-II, a sodium current inducer for mimicking long QT syndrome type 3, followed by exposure to test compounds. The observed changes in calcium dynamics following drug exposure demonstrated the utility of hPSC-CMs as a versatile model system for assessing both cardiotoxicity and drug efficacy. Overall, our findings highlight the potential of hPSC-CMs in advancing drug discovery and development, which offer a physiologically relevant platform for the preclinical screening of novel therapeutics.
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- 2024
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13. Protective Effects of a Combined Herbal Medicine against Amyotrophic Lateral Sclerosis-Associated Inflammation and Oxidative Stress
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Eun Jin Yang
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combined herbal medicine ,amyotrophic lateral sclerosis ,anti-inflammation ,anti-oxidation ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Despite extensive studies to identify effective curative drugs for amyotrophic lateral sclerosis (ALS), only riluzole and edaravone have been approved by the Food and Drug Administration. However, these drugs only delay disease progression and exhibit adverse effects, necessitating the development of more effective drugs. Herbal medicines are effective against incurable diseases with various pathogenic factors owing to their low toxicity and presence of multiple components, which target multiple organs. Therefore, we aimed to investigate whether a combined herbal medicine (CHM), comprising Gastrodia elata, Cnidium officinale Makino, and Ostericum koreanum, affects muscle function and motor neuron death in an animal model of ALS. We treated 8-week-old hSOD1G93A mice with 1 mg/g CHM, administered orally once daily for 6 weeks. Muscle function was measured via a footprint test. Biochemical analyses, including immunoblotting, western blotting, and immunohistochemistry, of the muscles (tibialis anterior and gastrocnemius) and spinal cord of hSOD1G93A mice were performed. The CHM treatment improved movement and reduced motor neuron loss in the mouse spinal cord. It also enhanced anti-inflammatory and anti-oxidant activities and regulated autophagy in the mouse muscles and spinal cord. These findings suggest that CHM has multi-active components that effectively target muscles and the spinal cord, delaying disease progression.
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- 2024
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14. The Impact of Ulmus macrocarpa Extracts on a Model of Sarcopenia-Induced C57BL/6 Mice
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Chan Ho Lee, Yeeun Kwon, Sunmin Park, TaeHee Kim, Min Seok Kim, Eun Ji Kim, Jae In Jung, Sangil Min, Kwang-Hyun Park, Jae Hun Jeong, and Sun Eun Choi
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Ulmus macrocarpa Hance ,sarcopenia ,muscle apoptosis ,muscle atrophy ,antioxidant ,anti-inflammatory ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Aging leads to tissue and cellular changes, often driven by oxidative stress and inflammation, which contribute to age-related diseases. Our research focuses on harnessing the potent anti-inflammatory and antioxidant properties of Korean Ulmus macrocarpa Hance, a traditional herbal remedy, to address muscle loss and atrophy. We evaluated the effects of Ulmus extract on various parameters in a muscle atrophy model, including weight, exercise performance, grip strength, body composition, muscle mass, and fiber characteristics. Additionally, we conducted Western blot and RT-PCR analyses to examine muscle protein regulation, apoptosis factors, inflammation, and antioxidants. In a dexamethasone-induced muscle atrophy model, Ulmus extract administration promoted genes related to muscle formation while reducing those associated with muscle atrophy. It also mitigated inflammation and boosted muscle antioxidants, indicating a potential improvement in muscle atrophy. These findings highlight the promise of Ulmus extract for developing pharmaceuticals and supplements to combat muscle loss and atrophy, paving the way for clinical applications.
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- 2024
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15. Effects of Functional Fatigue Protocol and Visual Information on Postural Control in Patients with Chronic Ankle Instability
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Kyungeon Kim, Hyunsoo Kim, Kyeongtak Song, Suji Yoon, Eun Ji Hong, Hyung Gyu Jeon, Kyoung Uk Oh, and Sae Yong Lee
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chronic ankle instability ,postural control ,functional fatigue ,sensory organization ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Chronic ankle instability (CAI) patients often exhibit postural control deficits and rely on visual information to maintain static balance to compensate for decreased proprioception. Fatigue impairs neuromuscular control, in addition to postural control, in CAI patients. However, whether functional fatiguing exercises alter postural control and sensory organization strategies during single-leg balance tests in CAI patients remains unclear. This study involved a controlled trial on 28 CAI patients in a laboratory setting. Each participant performed a single-leg balance test with eyes open (EO) and eyes closed (EC) before and after a functional fatigue protocol. Two-way repeated-measures ANOVA evaluated fatigue (pre- vs. post-fatigue) × vision (EO vs. EC) interactions for outcome variables. Additionally, paired-sample t-tests examined differences between two conditions (pre- vs. post-fatigue) for time-to-boundary (TTB) minima (%modulation). We found significant interactions between fatigue and vision conditions in ML and AP TTBmeans and AP TTBsds. %Modulations were significantly decreased after fatigue in AP TTBmean, ML TTBsd, and AP TTBsd. In conclusion, static postural control ability decreased after the functional fatigue protocol with EO, but was unchanged with EC. This suggests that decreased balance ability is more pronounced with EO under fatigue due to less visual dependence. This may increase ankle sprain incidence under fatigue.
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- 2024
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16. Development of a Normal Porcine Cell Line Growing in a Heme-Supplemented, Serum-Free Condition for Cultured Meat
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Yeon Ah Seo, Min Jeong Cha, Sehyeon Park, Seungki Lee, Ye Jin Lim, Dong Woo Son, Eun Ji Lee, Pil Kim, and Suhwan Chang
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porcine cell ,heme ,cultured meat ,serum free ,cytochrome P450 ,family 1 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
A key element for the cost-effective development of cultured meat is a cell line culturable in serum-free conditions to reduce production costs. Heme supplementation in cultured meat mimics the original meat flavor and color. This study introduced a bacterial extract generated from Corynebacterium that was selected for high-heme expression by directed evolution. A normal porcine cell line, PK15, was used to apply the bacterial heme extract as a supplement. Consistent with prior research, we observed the cytotoxicity of PK15 to the heme extract at 10 mM or higher. However, after long-term exposure, PK15 adapted to tolerate up to 40 mM of heme. An RNA-seq analysis of these heme-adapted PK15 cells (PK15H) revealed a set of altered genes, mainly involved in cell proliferation, metabolism, and inflammation. We found that cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), lactoperoxidase (LPO), and glutathione peroxidase 5 (GPX5) were upregulated in the PK15H heme dose dependently. When we reduced serum serially from 2% to serum free, we derived the PK15H subpopulation that was transiently maintained with 5–10 mM heme extract. Altogether, our study reports a porcine cell culturable in high-heme media that can be maintained in serum-free conditions and proposes a marker gene that plays a critical role in this adaptation process.
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- 2024
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17. Characterizing Glomerular Barrier Dysfunction with Patient-Derived Serum in Glomerulus-on-a-Chip Models: Unveiling New Insights into Glomerulonephritis
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Shin Young Kim, Yun Yeong Choi, Eun Jeong Kwon, Seungwan Seo, Wan Young Kim, Sung Hyuk Park, Seokwoo Park, Ho Jun Chin, Ki Young Na, and Sejoong Kim
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glomerulonephritis ,kidney glomerulus ,glomerulus-on-a-chip ,glomerular filtration barrier ,podocytes ,glomerular disease models ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.
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- 2024
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18. Discovery of Pathogenic Variants Associated with Idiopathic Recurrent Pregnancy Loss Using Whole-Exome Sequencing
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Jeong Yong Lee, JaeWoo Moon, Hae-Jin Hu, Chang Soo Ryu, Eun Ju Ko, Eun Hee Ahn, Young Ran Kim, Ji Hyang Kim, and Nam Keun Kim
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bioinformatics ,recurrent spontaneous abortion ,miscarriage ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Idiopathic recurrent pregnancy loss (RPL) is defined as at least two pregnancy losses before 20 weeks of gestation. Approximately 5% of pregnant couples experience idiopathic RPL, which is a heterogeneous disease with various causes including hormonal, chromosomal, and intrauterine abnormalities. Although how pregnancy loss occurs is still unknown, numerous biological factors are associated with the incidence of pregnancy loss, including genetic variants. Whole-exome sequencing (WES) was conducted on blood samples from 56 Korean patients with RPL and 40 healthy controls. The WES data were aligned by means of bioinformatic analysis, and the detected variants were annotated using machine learning tools to predict the pathogenicity of protein alterations. Each indicated variant was confirmed using Sanger sequencing. A replication study was also conducted in 112 patients and 114 controls. The Variant Effect Scoring Tool, Combined Annotation Dependent Depletion tool, Sorting Intolerant from Tolerant annotation tool, and various databases detected 10 potential variants previously associated with spontaneous abortion genes in patients by means of a bioinformatic analysis of WES data. Several variants were detected in more than one patient. Interestingly, several of the detected genes were functionally clustered, including some with a secretory function (mucin 4; MUC4; rs200737893 G>A and hyaluronan-binding protein 2; HABP2; rs542838125 G>T), in which growth arrest-specific 2 Like 2 (GAS2L2; rs140842796 C>T) and dynamin 2 (DNM2; rs763894364 G>A) are functionally associated with cell protrusion and the cytoskeleton. ATP Binding Cassette Subfamily C Member 6 (ABCC6) was the only gene with two variants. HABP2 (rs542838125 G>T), MUC4 (rs200737893 G>A), and GAS2L2 (rs140842796 C>T) were detected in only the patient group in the replication study. The combination of WES and machine learning tools is a useful method to detect potential variants associated with RPL. Using bioinformatic tools, we found 10 potential variants in 9 genes. WES data from patients are needed to better understand the causes of RPL.
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- 2024
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19. Fermentation characteristics and radical scavenging capacities of ginseng berry kombucha fermented by Saccharomyces cerevisiae and Gluconobacter oxydans
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Eun Jung Choi, Hee Ho Song, Ka Young Ko, Ki-Bae Hong, Hyung Joo Suh, and Yejin Ahn
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Ginseng berry kombucha ,Saccharomyces cerevisiae ,Gluconobacter oxydans ,ROS ,Agriculture (General) ,S1-972 ,Chemistry ,QD1-999 - Abstract
Abstract Kombucha is a healthy carbonated beverage made by fermenting tea extracts such as green tea and black tea through symbiotic culture of bacteria and yeast. In this study, fermentation characteristics and radical scavenging activity of ginseng berry kombucha (GBK) by Saccharomyces cerevisiae M-5 and Gluconobacter oxydans were measured. As fermentation time increased, pH decreased and titratable acidity increased. Reducing sugars decreased rapidly on day 3. Alcohol content increased dramatically during this period and then decreased. GBK showed increased radical scavenging activity and increased total flavonoid content on day 18 of fermentation compared to before fermentation. In particular, during GBK fermentation, the content of phenolic compounds such as gallic acid (2.09-fold) and chlorogenic acid (2.11-fold) increased, contributing to antioxidant activity. In addition, the major ginsenosides of GBK were identified as Rg2 (10.1 μg/mg) and Re (6.59 μg/mg), and the content of minor ginsenosides, which are easily absorbed forms, increased 2.19-fold by fermentation. GBK also extended survival in a Drosophila model treated with 15% hydrogen peroxide. GBK also reduced reactive oxygen species (p
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- 2023
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20. Integrating computational methods guided the discovery of phytochemicals as potential Pin1 inhibitors for cancer: pharmacophore modeling, molecular docking, MM-GBSA calculations and molecular dynamics studies
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Abdulrahim A. Alzain, Fatima A. Elbadwi, Tagyedeen H. Shoaib, Asmaa E. Sherif, Wadah Osman, Ahmed Ashour, Gamal A. Mohamed, Sabrin R. M. Ibrahim, Eun Joo Roh, and Ahmed H. E. Hassan
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Pin1 ,cancer ,pharmacophore modeling ,molecular docking ,MM-GBSA ,molecular dynamics ,Chemistry ,QD1-999 - Abstract
Pin1 is a pivotal player in interactions with a diverse array of phosphorylated proteins closely linked to critical processes such as carcinogenesis and tumor suppression. Its axial role in cancer initiation and progression, coupled with its overexpression and activation in various cancers render it a potential candidate for the development of targeted therapeutics. While several known Pin1 inhibitors possess favorable enzymatic profiles, their cellular efficacy often falls short. Consequently, the pursuit of novel Pin1 inhibitors has gained considerable attention in the field of medicinal chemistry. In this study, we employed the Phase tool from Schrödinger to construct a structure-based pharmacophore model. Subsequently, 449,008 natural products (NPs) from the SN3 database underwent screening to identify compounds sharing pharmacophoric features with the native ligand. This resulted in 650 compounds, which then underwent molecular docking and binding free energy calculations. Among them, SN0021307, SN0449787 and SN0079231 showed better docking scores with values of −9.891, −7.579 and −7.097 kcal/mol, respectively than the reference compound (−6.064 kcal/mol). Also, SN0021307, SN0449787 and SN0079231 exhibited lower free binding energies (−57.12, −49.81 and −46.05 kcal/mol, respectively) than the reference ligand (−37.75 kcal/mol). Based on these studies, SN0021307, SN0449787, and SN0079231 showed better binding affinity that the reference compound. Further the validation of these findings, molecular dynamics simulations confirmed the stability of the ligand-receptor complex for 100 ns with RMSD ranging from 0.6 to 1.8 Å. Based on these promising results, these three phytochemicals emerge as promising lead compounds warranting comprehensive biological screening in future investigations. These compounds hold great potential for further exploration regarding their efficacy and safety as Pin1 inhibitors, which could usher in new avenues for combating cancer.
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- 2024
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21. Comparison of the Efficacy between Pemetrexed plus Platinum and Non-Pemetrexed plus Platinum as First-Line Treatment in Patients with Wild-Type Epidermal Growth Factor Receptor Nonsquamous Non-Small Cell Lung Cancer: A Retrospective Analysis
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Eun J oo Kang, Sang C heul Oh, Gyu Young Hur, Jun S uk Kim, Jae J eong Shim, Kyung H oon Min, Kyung Ho Kang, Sung Y ong Lee, and Jae H ong Seo
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Male ,Oncology ,Lung Neoplasms ,medicine.medical_treatment ,Deoxycytidine ,Carboplatin ,chemistry.chemical_compound ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,Drug Discovery ,Pharmacology (medical) ,030212 general & internal medicine ,Etoposide ,Aged, 80 and over ,Vinorelbine ,General Medicine ,Middle Aged ,Prognosis ,ErbB Receptors ,Survival Rate ,Infectious Diseases ,Pemetrexed ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Adenocarcinoma ,Irinotecan ,Vinblastine ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Lung cancer ,Survival rate ,Aged ,Neoplasm Staging ,Retrospective Studies ,Pharmacology ,Chemotherapy ,business.industry ,medicine.disease ,Gemcitabine ,chemistry ,Mutation ,Carcinoma, Large Cell ,Camptothecin ,Cisplatin ,business ,Follow-Up Studies - Abstract
Background: Despite the development of molecular research and targeted therapy, patients with wild-type epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) still receive platinum doublet chemotherapy as the standard first-line treatment. We investigated the efficacy of first-line regimens in patients with wild-type EGFR nonsquamous NSCLC. Methods: We retrospectively analyzed the efficacy of various platinum doublet regimens as first-line treatments. Between 2007 and 2013, a total of 165 patients with wild-type EGFR nonsquamous NSCLC were included in this study. Results: Seventy-one (43.0%) patients were treated with pemetrexed plus platinum (PP) and 94 (57.0%) with non-pemetrexed plus platinum (NPP). The overall response rate was not different between the PP- and NPP-treated groups (26.8 vs. 28.7%, respectively; p = 0.78). The median progression-free survival (PFS) and overall survival (OS) also showed no differences between the two treatment groups (p = 0.12 for PFS, p = 0.42 for OS). The median PFS and OS for the PP group were 4.6 months (95% CI, 3.8-5.4) and 18.7 months (95% CI, 11.7-25.8), respectively, and for the NPP group, they were 4.2 months (95% CI, 3.4-5.0) and 12.2 months (95% CI, 10.3-14.1), respectively. In the subgroup analysis, most subgroups showed no significant difference in PFS and OS between the two treatment groups. Conclusion: Our data showed that the efficacy of various platinum doublet regimens was similar in patients with wild-type EGFR nonsquamous NSCLC.
- Published
- 2015
22. Gambogic Acid and Its Analogs Inhibit Gap Junctional Intercellular Communication
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Eun J. Choi, Joo H. Yeo, Sei M. Yoon, and Jinu Lee
- Subjects
0301 basic medicine ,connexin ,tetrahydrogambogic acid ,Carbenoxolone ,Connexin ,dihydrogambogic acid ,Redox ,gap junction ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Pharmacology (medical) ,IC50 ,Original Research ,Pharmacology ,gambogic acid ,lcsh:RM1-950 ,Gap junction ,Cx40 ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,chemistry ,030220 oncology & carcinogenesis ,Biophysics ,Phosphorylation ,Gambogic acid ,Intracellular ,medicine.drug - Abstract
Gap junctions (GJs) are intercellular channels composed of connexins. Cellular molecules smaller than 1 kDa can diffuse through GJs by a process termed gap junctional intercellular communication (GJIC), which plays essential roles in various pathological and physiological conditions. Gambogic acid (GA), a major component of a natural yellow dye, has been used as traditional medicine and has been reported to have various therapeutic effects, including an anti-cancer effect. In this study, two different GJ assay methods showed that GA and its analogs inhibited GJIC. The inhibition was rapidly reversible and was not mediated by changes in surface expression or S368 phosphorylation of Cx43, cellular calcium concentration, or redox state. We also developed an assay system to measure the intercellular communication induced by Cx40, Cx30, and Cx43. Dihydrogambogic acid (D-GA) potently inhibited GJIC by Cx40 (IC50 = 5.1 μM), whereas the IC50 value of carbenoxolone, which is known as a broad spectrum GJIC inhibitor, was 105.2 μM. Thus, D-GA can act as a pharmacological tool for the inhibition of Cx40.
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- 2018
23. Pharmacokinetics and brain distribution of the therapeutic peptide liraglutide by a novel LC–MS/MS analysis
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Hyeon Seok Oh, Minkyu Choi, Tae Suk Lee, Yejin An, Eun Ji Park, Tae Hwan Kim, Soyoung Shin, and Beom Soo Shin
- Subjects
Glucagon-like peptide-1 ,Liraglutide ,LC–MS/MS ,Pharmacokinetics ,Bioavailability ,Brain distribution ,Chemistry ,QD1-999 ,Analytical chemistry ,QD71-142 - Abstract
Abstract Liraglutide is a glucagon-like peptide-1 (GLP-1) analog that has been utilized for the treatment of type 2 diabetes mellitus. Liraglutide at a higher dose also shows beneficial effects in weight loss, which prompted its widespread use as an anti-obesity drug. The potential of liraglutide to treat Alzheimer’s disease and cognitive impairment has also been suggested. Nevertheless, the pharmacokinetics of liraglutide, including its distribution to the brain, has not been fully characterized. Therefore, this study aimed to develop a simple and sensitive bioanalytical method using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and determine the pharmacokinetics and brain distribution of liraglutide in rats. Liraglutide in the rat plasma and brain tissue homogenates was extracted by protein precipitation using methanol. A gradient elution profile was used for chromatographic separation with mobile phases comprising 0.3% formic acid in water and 0.3% formic acid in acetonitrile. The mass spectrometry was operated in the positive electrospray ionization with multiple reaction monitoring mode. The lower limit of quantification of the present LC–MS/MS was 1 ng/mL in the plasma and 2 ng/mL in the brain tissue. Following intravenous injection (0.05 mg/kg, n = 5), plasma concentrations of liraglutide decreased monoexponentially with an average half-life of 3.67 h. The estimated absolute bioavailability of liraglutide after subcutaneous injection was 13.16%. Brain distribution of liraglutide was not significant, with the tissue-to-plasma partition coefficient (K p) of liraglutide less than 0.00031. However, the concentrations of liraglutide were significantly different in the different brain regions following IV injection. In the brain, liraglutide concentrations were the highest in the hypothalamus, followed by the cerebellum and cerebrum. The present LC–MS/MS assay and the pharmacokinetic results may be helpful to understand better the effect of liraglutide in the brain for further preclinical and clinical studies of liraglutide.
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- 2023
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24. Atroposelective desymmetrization of 2-arylresorcinols via Tsuji-Trost allylation
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Sangji Kim, Aram Kim, Chanhee Lee, Junsoo Moon, Eun Jeong Hong, Duck-Hyung Lee, and Yongseok Kwon
- Subjects
Chemistry ,QD1-999 - Abstract
Desymmetrization of symmetric biaryls is an efficient but underexplored way to approach axially chiral molecules. Here, the authors report the atroposelective desymmetrization of 2- arylresorcinols via chiral palladium complex-catalyzed allylic alkylation.
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- 2023
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25. Gene Expression and DNA Methylation Profiling Suggest Potential Biomarkers for Azacitidine Resistance in Myelodysplastic Syndrome
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Da Yeon Kim, Dong-Yeop Shin, Somi Oh, Inho Kim, and Eun Ju Kim
- Subjects
myelodysplastic syndrome ,azacitidine ,resistance ,DNA methylation ,biomarkers ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Myelodysplastic syndrome/neoplasm (MDS) comprises a group of heterogeneous hematopoietic disorders that present with genetic mutations and/or cytogenetic changes and, in the advanced stage, exhibit wide-ranging gene hypermethylation. Patients with higher-risk MDS are typically treated with repeated cycles of hypomethylating agents, such as azacitidine. However, some patients fail to respond to this therapy, and fewer than 50% show hematologic improvement. In this context, we focused on the potential use of epigenetic data in clinical management to aid in diagnostic and therapeutic decision-making. First, we used the F-36P MDS cell line to establish an azacitidine-resistant F-36P cell line. We performed expression profiling of azacitidine-resistant and parental F-36P cells and used biological and bioinformatics approaches to analyze candidate azacitidine-resistance-related genes and pathways. Eighty candidate genes were identified and found to encode proteins previously linked to cancer, chronic myeloid leukemia, and transcriptional misregulation in cancer. Interestingly, 24 of the candidate genes had promoter methylation patterns that were inversely correlated with azacitidine resistance, suggesting that DNA methylation status may contribute to azacitidine resistance. In particular, the DNA methylation status and/or mRNA expression levels of the four genes (AMER1, HSPA2, NCX1, and TNFRSF10C) may contribute to the clinical effects of azacitidine in MDS. Our study provides information on azacitidine resistance diagnostic genes in MDS patients, which can be of great help in monitoring the effectiveness of treatment in progressing azacitidine treatment for newly diagnosed MDS patients.
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- 2024
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26. MicroRNA-135b-5p Is a Pathologic Biomarker in the Endothelial Cells of Arteriovenous Malformations
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Joon Seok Lee, Gyeonghwa Kim, Jong Ho Lee, Jeong Yeop Ryu, Eun Jung Oh, Hyun Mi Kim, Suin Kwak, Keun Hur, and Ho Yun Chung
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arteriovenous malformation ,microRNA-135b-5p ,endothelial cells ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Arteriovenous malformations (AVMs) are congenital vascular anomalies with a poor prognosis. AVMs are considered intractable diseases, as there is no established approach for early diagnosis and treatment. Therefore, this study aimed to provide new evidence by analyzing microRNAs (miRNAs) associated with AVM. We present fundamental evidence for the early diagnosis and treatment of AVM by analyzing miRNAs in the endothelial cells of AVMs. This study performed sequencing and validation of miRNAs in endothelial cells from normal and AVM tissues. Five upregulated and two downregulated miRNAs were subsequently analyzed under hypoxia and vascular endothelial growth factor (VEGF) treatment by one-way analysis of variance (ANOVA). Under hypoxic conditions, miR-135b-5p was significantly upregulated in the AVM compared to that under normal conditions, corresponding to increased endothelial activity (p-value = 0.0238). VEGF treatment showed no significant increase in miR-135b-5p under normal conditions, however, a surge in AVM was observed. Under both hypoxia and VEGF treatment, comparison indicated a downregulation of miR-135b-5p in AVM. Therefore, miR-135b-5p was assumed to affect the pathophysiological process of AVM and might play a vital role as a potential biomarker of AVMs for application related to diagnosis and treatment.
- Published
- 2024
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27. Upregulation of EMR1 (ADGRE1) by Tumor-Associated Macrophages Promotes Colon Cancer Progression by Activating the JAK2/STAT1,3 Signaling Pathway in Tumor Cells
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Rokeya Akter, Rackhyun Park, Soo Kyung Lee, Eun ju Han, Kyu-Sang Park, Junsoo Park, and Mee-Yon Cho
- Subjects
colon cancer ,EMR1/ADGRE1 ,macrophages ,JAK2/STAT1,3 signaling ,lymph node metastasis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Previously, we reported that epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR1/ADGRE1) is abnormally expressed in colon cancer (CC) and is a risk factor for lymph node metastasis (LNM) and poor recurrence-free survival in patients with abundant tumor-associated macrophages (TAMs). However, the signaling pathways associated with EMR1 expression in CC progression remain unclear. In this study, we aimed to explore the role of EMR1 and its signaling interactions with macrophages in CC progression. Spatial transcriptomics of pT3 microsatellite unstable CC tissues revealed heightened Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in EMR1-HL CC with LNM compared to EMR1-N CC without LNM. Through in vitro coculture of CC cells with macrophages, EMR1 expression by CC cells was found to be induced by TAMs, ultimately interacting with upregulated JAK/STAT signaling, increasing cell proliferation, migration, and motility, and reducing apoptosis. JAK2/STAT3 inhibition decreased the levels of EMR1, JAK2, STAT1, and STAT3, significantly impeded the proliferation, migration, and mobility of cells, and increased the apoptosis of EMR1+ CC cells compared to their EMR1KO counterparts. Overall, TAMs-induced EMR1 upregulation in CC cells may promote LNM and CC progression via JAK2/STAT1,3 signaling upregulation. This study provides further insights into the molecular mechanisms involving macrophages and intracellular EMR1 expression in CC progression, suggesting its clinical significance and offering potential interventions to enhance patient outcomes.
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- 2024
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28. Evaluating the Anti-Osteoarthritis Potential of Standardized Boswellia serrata Gum Resin Extract in Alleviating Knee Joint Pathology and Inflammation in Osteoarthritis-Induced Models
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Yean-Jung Choi, Jae In Jung, Jaewoo Bae, Jae Kyoung Lee, and Eun Ji Kim
- Subjects
osteoarthritis ,Boswellia serrata ,monosodium iodoacetate ,type II collagen ,aggrecan ,cytokines ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Osteoarthritis is a widespread chronic degenerative disease marked by the deterioration of articular cartilage, modifications in subchondral bone, and a spectrum of symptoms, including pain, stiffness, and disability. Ultimately, this condition impairs the patient’s quality of life. This study aimed to evaluate the therapeutic efficacy of standardized Boswellia serrata gum resin extract (BSRE) in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. A total of 60 rats were allocated into six groups: normal control group (NC), osteoarthritis control (injected with MIA, OC), O + B50 (injected with MIA and treated with 50 mg/kg body weight (BW) BSRE), O + B75 (injected with MIA and treated with 75 mg/kg BW BSRE), O + B100 (injected with MIA and treated with 100 mg/kg BW BSRE), and O + M (injected with MIA and treated with 150 mg/kg BW methyl sulfonyl methane). Several parameters, including knee joint swelling, histopathological changes, and the expression of collagen type II alpha 1 (COL2A1) and aggrecan, were comprehensively assessed. Concurrently, the serum levels and mRNA expression of inflammatory mediators, cytokines, and matrix metalloproteinases (MMPs) were analyzed in both the serum and knee joint synovium. The results demonstrated that BSRE significantly mitigated knee joint swelling, cartilage destruction, and tissue deformation. Notably, BSRE administration markedly upregulated the expression of COL2A1 and aggrecan while concurrently reducing levels of nitric oxide, prostaglandin E2, leukotriene B4, interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Furthermore, a substantial decrease was observed in the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, IL-6, TNF-α and MMP-3 and -13, thereby indicating promising therapeutic implications for osteoarthritis. In conclusion, BSRE exhibited anti-inflammatory properties and inhibited cartilage matrix degradation in a rat model of MIA-induced osteoarthritis, with the O + B100 group showing significant reductions in swelling and notable improvements in joint cartilage damage. These findings illuminate the preventive and therapeutic potential of BSRE for osteoarthritis treatment, emphasizing the criticality of exhaustive evaluation of novel compounds.
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- 2024
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29. Thermal decarboxylation of acidic cannabinoids in Cannabis species: identification of transformed cannabinoids by UHPLC-Q/TOF–MS
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Chaeyoung Seo, Minsun Jeong, Sangin Lee, Eun Jae Kim, Soohyang Rho, Mansoo Cho, Yong Sup Lee, and Jongki Hong
- Subjects
Cannabis species ,Cannabidiolic acid (CBDA) ,Thermal reaction ,Psychotropic THC ,UHPLC-Q/TOF–MS ,Chemistry ,QD1-999 ,Analytical chemistry ,QD71-142 - Abstract
Abstract Decarboxylation of cannabidiolic acid (CBDA) is an important step for efficient production of the active pharmaceutical component cannabidiol (CBD) in Cannabis species. Acidic cannabinoids (ACBs) can be easily transformed into neutral cannabinoids via loss of carbon dioxide when exposed to heat. During the thermal process, several transformed products including psychotropic △ 9-tetrahydrocannabinol (△ 9-THC) and its isomers were produced through decarboxylation, hydration, isomerization, and oxidation, as identified by ultra-high-performance liquid chromatography quadrupole/time-of-flight mass spectrometry (UHPLC-Q/TOF MS). Their identification was carried out using authenticated standards and interpreting the MS/MS fragmentations. To investigate thermal decarboxylation, CBDA was extracted and isolated from inflorescence of Cannabis by ultrasonication extraction and two-step column chromatography. To investigate the decarboxylation yield of isolated CBDA and ACBs in Cannabis extract, samples were examined over a range of reaction temperatures (110–130 °C) and times (5–60 min). Time profiles of CBDA degradation and CBD formation were obtained as functions of the reaction temperature. In particular, most of the CBDA was converted into CBD at 130 °C for 20 min; this CBD was partially transformed to psychotropic THC isomers via cyclization. In addition to THC isomers, cannabielsoin acid (CBEA) and cannabielsoin (CBE) were also observed as minor oxidative transformed products. Based on structural identification and profiling data, thermal transformation pathways of CBDA are plausibly suggested. The results of decarboxylation of ACBs will provide important information on production of neutral cannabinoids, especially CBD, in Cannabis plants and quality control of Cannabis-based products in pharmaceutical and cosmetic industries.
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- 2022
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30. Therapeutic Applications of Ginseng Natural Compounds for Health Management
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Syed Sayeed Ahmad, Khurshid Ahmad, Ye Chan Hwang, Eun Ju Lee, and Inho Choi
- Subjects
ginseng ,compounds ,treatment ,disease ,mechanism ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Ginseng is usually consumed as a daily food supplement to improve health and has been shown to benefit skeletal muscle, improve glucose metabolism, and ameliorate muscle-wasting conditions, cardiovascular diseases, stroke, and the effects of aging and cancers. Ginseng has also been reported to help maintain bone strength and liver (digestion, metabolism, detoxification, and protein synthesis) and kidney functions. In addition, ginseng is often used to treat age-associated neurodegenerative disorders, and ginseng and ginseng-derived natural products are popular natural remedies for diseases such as diabetes, obesity, oxidative stress, and inflammation, as well as fungal, bacterial, and viral infections. Ginseng is a well-known herbal medication, known to alleviate the actions of several cytokines. The article concludes with future directions and significant application of ginseng compounds for researchers in understanding the promising role of ginseng in the treatment of several diseases. Overall, this study was undertaken to highlight the broad-spectrum therapeutic applications of ginseng compounds for health management.
- Published
- 2023
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31. Artemisia annua L. Polyphenols Enhance the Anticancer Effect of β-Lapachone in Oxaliplatin-Resistant HCT116 Colorectal Cancer Cells
- Author
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Eun Joo Jung, Hye Jung Kim, Sung Chul Shin, Gon Sup Kim, Jin-Myung Jung, Soon Chan Hong, Choong Won Kim, and Won Sup Lee
- Subjects
Artemisia annua L. polyphenols ,β-lapachone ,phytochemical ,anticancer effect ,oxaliplatin-resistant ,colorectal cancer ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Recent studies suggest that the anticancer activity of β-lapachone (β-Lap) could be improved by different types of bioactive phytochemicals. The aim of this study was to elucidate how the anticancer effect of β-Lap is regulated by polyphenols extracted from Korean Artemisia annua L. (pKAL) in parental HCT116 and oxaliplatin-resistant (OxPt-R) HCT116 colorectal cancer cells. Here, we show that the anticancer effect of β-Lap is more enhanced by pKAL in HCT116-OxPt-R cells than in HCT116 cells via a CCK-8 assay, Western blot, and phase-contrast microscopy analysis of hematoxylin-stained cells. This phenomenon was associated with the suppression of OxPt-R-related upregulated proteins including p53 and β-catenin, the downregulation of cell survival proteins including TERT, CD44, and EGFR, and the upregulation of cleaved HSP90, γ-H2AX, and LC3B-I/II. A bioinformatics analysis of 21 proteins regulated by combined treatment of pKAL and β-Lap in HCT116-OxPt-R cells showed that the enhanced anticancer effect of β-Lap by pKAL was related to the inhibition of negative regulation of apoptotic process and the induction of DNA damage through TERT, CD44, and EGFR-mediated multiple signaling networks. Our results suggest that the combination of pKAL and β-Lap could be used as a new therapy with low toxicity to overcome the OxPt-R that occurred in various OxPt-containing cancer treatments.
- Published
- 2023
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32. Loliolide in Sargassum horneri Alleviates Ultrafine Urban Particulate Matter (PM 0.1)-Induced Inflammation in Human RPE Cells
- Author
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Eun Jeoung Lee, Sol Lee, Hyun-Jae Jang, and Wonbeak Yoo
- Subjects
Sargassum horneri ,ultrafine urban particulate matters ,ARPE-19 ,anti-inflammation ,MAPK/NF-ĸB ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Owing to increasing air pollution due to industrial development, fine dust has been associated with threatening public health. In particular, ultrafine urban particulate matter (uf-UP, PM 0.1) can easily enter our bodies, causing inflammation-related diseases. Therefore, in the present study, we evaluated the effects of hydrothermal extracts of Sargassum horneri and its bioactive compound, loliolide, on uf-UP-induced inflammation as a potential treatment strategy for retinal disorders. Human retinal pigment epithelial cells (ARPE-19) stimulated with TNF-α or uf-UPs were treated with S. horneri extract and loliolide. S. horneri extracts exhibited anti-inflammatory effects on uf-UP-induced inflammation without cell toxicity through downregulating the mRNA expression of MCP-1, IL-8, IL-6, and TNF-α. UPLC-QTOF/MS analysis confirmed that the hydrothermal extract of S. horneri contained loliolide, which has anti-inflammatory effects. Loliolide effectively reduced the mRNA expression and production of proinflammatory chemokines (IL-8) and cytokines (IL-1β and IL-6) by downregulating the MAPK/NF-ĸB signaling pathway on TNF-α-stimulated inflammatory ARPE-19 cells. These effects were further confirmed in inflammatory ARPE-19 cells after stimulation with uf-UPs. Collectively, these results suggested the application of S. horneri as a functional ingredient for treating ocular disorders caused by particular matters.
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- 2023
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33. Comparative RNA-Seq Analysis Revealed Tissue-Specific Splicing Variations during the Generation of the PDX Model
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Eun Ji Lee, Seung-Jae Noh, Huiseon Choi, Min Woo Kim, Su Jin Kim, Yeon Ah Seo, Ji Eun Jeong, Inkyung Shin, Jong-Seok Kim, Jong-Kwon Choi, Dae-Yeon Cho, and Suhwan Chang
- Subjects
alternative splicing ,PDX model ,tissue specificity ,RNA-seq ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Tissue-specific gene expression generates fundamental differences in the function of each tissue and affects the characteristics of the tumors that are created as a result. However, it is unclear how much the tissue specificity is conserved during grafting of the primary tumor into an immune-compromised mouse model. Here, we performed a comparative RNA-seq analysis of four different primary-patient derived xenograft (PDX) tumors. The analysis revealed a conserved RNA biotype distribution of primary−PDX pairs, as revealed by previous works. Interestingly, we detected significant changes in the splicing pattern of PDX, which was mainly comprised of skipped exons. This was confirmed by splicing variant-specific RT-PCR analysis. On the other hand, the correlation analysis for the tissue-specific genes indicated overall strong positive correlations between the primary and PDX tumor pairs, with the exception of gastric cancer cases, which showed an inverse correlation. These data propose a tissue-specific change in splicing events during PDX formation as a variable factor that affects primary−PDX integrity.
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- 2023
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34. Genetic Correlation of miRNA Polymorphisms and STAT3 Signaling Pathway with Recurrent Implantation Failure in the Korean Population
- Author
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Jung Hun Lee, Eun Hee Ahn, Min Jung Kwon, Chang Su Ryu, Yong Hyun Ha, Eun Ju Ko, Jeong Yong Lee, Ji Young Hwang, Ji Hyang Kim, Young Ran Kim, and Nam Keun Kim
- Subjects
single nucleotide polymorphism ,recurrent implantation failure ,STAT3 ,microRNA ,in vitro fertilization ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The growing prevalence of in vitro fertilization-embryo transfer procedures has resulted in an increased incidence of recurrent implantation failure (RIF), necessitating focused research in this area. STAT3, a key factor in maternal endometrial remodeling and stromal proliferation, is crucial for successful embryo implantation. While the relationship between STAT3 and RIF has been studied, the impact of single nucleotide polymorphisms (SNPs) in miRNAs, well-characterized gene expression modulators, on STAT3 in RIF cases remains uncharacterized. Here, we investigated 161 RIF patients and 268 healthy control subjects in the Korean population, analyzing the statistical association between miRNA genetic variants and RIF risk. We aimed to determine whether SNPs in specific miRNAs, namely miR-218-2 rs11134527 G>A, miR-34a rs2666433 G>A, miR-34a rs6577555 C>A, and miR-130a rs731384 G>A, were significantly associated with RIF risk. We identified a significant association between miR-34a rs6577555 C>A and RIF prevalence (implantation failure [IF] ≥ 2: adjusted odds ratio [AOR] = 2.264, 95% CI = 1.007–5.092, p = 0.048). These findings suggest that miR-34a rs6577555 C>A may contribute to an increased susceptibility to RIF. However, further investigations are necessary to elucidate the precise mechanisms underlying the role of miR-34a rs6577555 C>A in RIF. This study sheds light on the genetic and molecular factors underlying RIF, offering new avenues for research and potential advancements in the diagnosis and treatment of this complex condition.
- Published
- 2023
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35. Posaconazole Serum Concentrations among Cardiothoracic Transplant Recipients: Factors Impacting Trough Levels and Correlation with Clinical Response to Therapy
- Author
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Fernanda P. Silveira, Jay K. Bhama, Eun J. Kwak, Christian Bermudez, Rima C. Abdel Massih, Joseph M. Pilewski, Aniket Vadnerkar, Maria Crespo, M. Hong Nguyen, Ryan K. Shields, Yoshiya Toyoda, and Cornelius J. Clancy
- Subjects
Adult ,Male ,medicine.medical_specialty ,Posaconazole ,Antifungal Agents ,Response to therapy ,Trough (economics) ,Gastroenterology ,Biological fluid ,Oral administration ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Aged ,Pharmacology ,Chemistry ,Middle Aged ,Triazoles ,Serum concentration ,Surgery ,Infectious Diseases ,Triazole derivatives ,Heart Transplantation ,Female ,medicine.drug - Abstract
Fifty-six serum posaconazole trough levels were measured in 17 cardiothoracic transplant recipients. Initial levels were ≤0.5, 0.51 to 0.99, and ≥1 μg/ml for 47, 29, and 24% of patients, respectively. Median trough levels associated with therapeutic success were higher than those associated with failure (1.55 versus 0.34 μg/ml; P = 0.006). Patients with levels consistently >0.5 μg/ml were more likely to have successful outcome ( P = 0.055). Age ≥65 years, oral administration, and absence of proton pump inhibitors were associated with higher levels of posaconazole ( P = 0.006, 0.006, and 0.001, respectively).
- Published
- 2011
36. Distinctive inhibition of O-GlcNAcase isoforms by an [alpha]-GlcNAc thiolsufonate
- Author
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Eun J. Kim, Amorelli, Benjamin, Abdo, Mohannad, Thomas, Craig J., Love, Dona C., Knapp, Spencer, and Hanover, John A.
- Subjects
Crystallography -- Analysis ,Gene expression -- Research ,Proteins -- Structure ,Proteins -- Research ,Chemistry - Abstract
The inhibition characteristics of [alpha]-linked 2-acetamido-2-deoxy-[beta]-D-glucopyranosyl (GlcNAc) thiolsulfonate to inhibit an enzyme that specifically processes [beta]-linked substrates is described.
- Published
- 2007
37. Voriconazole Pharmacokinetics in Liver Transplant Recipients
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Blair Capitano, Kelong Han, D. Blisard, M. Romkes, Amadeo Marcos, Peter K. Linden, H. J. Johnson, Shahid Husain, Brian A. Potoski, Raman Venkataramanan, David L. Paterson, and Eun J. Kwak
- Subjects
Adult ,Male ,medicine.medical_specialty ,Antifungal Agents ,Genotype ,Aspartate transaminase ,Pharmacology ,Gastroenterology ,Pharmacokinetics ,Internal medicine ,medicine ,Aspergillosis ,Humans ,Pharmacology (medical) ,Trough Concentration ,Prospective Studies ,Aged ,Volume of distribution ,Voriconazole ,biology ,Chemistry ,Middle Aged ,Triazoles ,Liver Transplantation ,Bioavailability ,Pyrimidines ,Infectious Diseases ,Area Under Curve ,biology.protein ,Trough level ,Female ,Liver function ,medicine.drug - Abstract
The objective of this study was to evaluate the pharmacokinetics of voriconazole and the potential correlations between pharmacokinetic parameters and patient variables in liver transplant patients on a fixed-dose prophylactic regimen. Multiple blood samples were collected within one dosing interval from 15 patients who were initiated on a prophylactic regimen of voriconazole at 200 mg enterally (tablets) twice daily starting immediately posttransplant. Voriconazole plasma concentrations were measured using high-pressure liquid chromatography (HPLC). Noncompartmental pharmacokinetic analysis was performed to estimate pharmacokinetic parameters. The mean apparent systemic clearance over bioavailability (CL/ F ), apparent steady-state volume of distribution over bioavailability ( V ss / F ), and half-life ( t 1/2 ) were 5.8 ± 5.5 liters/h, 94.5 ± 54.9 liters, and 15.7 ± 7.0 h, respectively. There was a good correlation between the area under the concentration-time curve from 0 h to infinity (AUC 0-∞ ) and trough voriconazole plasma concentrations. t 1/2 , maximum drug concentration in plasma ( C max ), trough level, AUC 0-∞ , area under the first moment of the concentration-time curve from 0 h to infinity (AUMC 0-∞ ), and mean residence time from 0 h to infinity (MRT 0-∞ ) were significantly correlated with postoperative time. t 1/2 , λ, AUC 0-∞ , and CL/ F were significantly correlated with indices of liver function (aspartate transaminase [AST], total bilirubin, and international normalized ratio [INR]). The C max , last concentration in plasma at 12 h ( C last ), AUMC 0-∞ , and MRT 0-∞ were significantly lower in the presence of deficient CYP2C19*2 alleles. Donor characteristics had no significant correlation with any of the pharmacokinetic parameters estimated. A fixed dosing regimen of voriconazole results in a highly variable exposure of voriconazole in liver transplant patients. Given that trough voriconazole concentration is a good measure of drug exposure (AUC), the voriconazole dose can be individualized based on trough concentration measurements in liver transplant patients.
- Published
- 2010
38. Synthesis of Highly Antibacterial Nanocrystalline Trivalent Silver Polydiguanide
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Yu Kyung Tak, Eun J. Yoon, Joon Myong Song, Sukdeb Pal, and Eung Chil Choi
- Subjects
Inorganic chemistry ,Metal Nanoparticles ,Nanoparticle ,Gram-Positive Bacteria ,Ligands ,Silver sulfadiazine ,Biochemistry ,Catalysis ,Silver nanoparticle ,Metal ,Colloid and Surface Chemistry ,Drug Stability ,Gram-Negative Bacteria ,medicine ,Microemulsion ,Ligand ,Chemistry ,Silver Compounds ,General Chemistry ,Nanocrystalline material ,Anti-Bacterial Agents ,visual_art ,visual_art.visual_art_medium ,Nanoparticles ,Emulsions ,Antibacterial activity ,Oxidation-Reduction ,Nuclear chemistry ,medicine.drug - Abstract
Highly monodispersed nanoparticles of a trivalent silver polydiguanide complex are synthesized by oxidation of the monovalent silver, followed by stabilization of the oxidized higher-valent metal through complexation with a polydiguanide ligand in a reverse microemulsion at room temperature. The synthesized nanoparticles have excellent photostability and displayed superior antibacterial activity toward Gram-positive and Gram-negative prokaryotes of clinical interest in vitro compared to silver sulfadiazine. These nanoparticles may serve as a new generation antibacterial metallopharmaceutical in wound care.
- Published
- 2009
39. Galactomannan detection in bronchoalveolar lavage fluid
- Author
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M. Hong Nguyen and Eun J. Kwak
- Subjects
education.field_of_study ,medicine.diagnostic_test ,business.industry ,Population ,Invasive pulmonary aspergillosis ,Neutropenia ,bacterial infections and mycoses ,Aspergillosis ,medicine.disease ,respiratory tract diseases ,Galactomannan ,chemistry.chemical_compound ,Infectious Diseases ,Bronchoalveolar lavage ,chemistry ,Immunology ,medicine ,In patient ,skin and connective tissue diseases ,education ,business ,Target organ - Abstract
Prompt diagnosis of invasive pulmonary aspergillosis (IPA) remains a challenge. Galactomannan (GM) assay in serum has been incorporated into diagnostic criteria for IPA, but its performance varies depending on the population in which the test is used. GM assay on bronchoalveolar lavage (BAL) fluid aims to improve upon the test by applying it directly on samples from the target organ. The studies that have examined the utility of BAL-GM are a heterogeneous group, but the results are intriguing, especially in patients who are at risk for IPA from causes other than hematologic malignancy and neutropenia. BAL-GM had sensitivities ranging from 60% to 100% in this group, often far exceeding the performance of serum GM assay. The test shows promise as a useful adjunctive diagnostic modality in the diagnosis of IPA.
- Published
- 2008
40. An Angiogenesis Inhibitor, 2-Methoxyestradiol, Involutes Rat Collagen-Induced Arthritis and Suppresses Gene Expression of Synovial Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor
- Author
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Eun J. Park, Ernest Brahn, John K. Lee, Stacy M. Plum, William E. Fogler, and Mona Lisa Banquerigo
- Subjects
medicine.medical_specialty ,Angiogenesis ,Immunology ,Basic fibroblast growth factor ,Gene Expression ,Arthritis ,Endothelial Growth Factors ,chemistry.chemical_compound ,Rheumatology ,Internal medicine ,Synovitis ,von Willebrand Factor ,medicine ,Animals ,Immunology and Allergy ,2-Methoxyestradiol ,Gastric Lavage ,Infusion Pumps ,Autoantibodies ,Estradiol ,Neovascularization, Pathologic ,business.industry ,Synovial Membrane ,Rats, Inbred Strains ,medicine.disease ,Arthritis, Experimental ,Immunohistochemistry ,Tubulin Modulators ,Rats ,Angiogenesis inhibitor ,Radiography ,Vascular endothelial growth factor ,Disease Models, Animal ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Fibroblast Growth Factor 2 ,Collagen ,Synovial membrane ,business ,medicine.drug - Abstract
ObjectiveRheumatoid arthritis (RA) pannus may be dependent on angiogenesis and several critical growth factors including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). 2-Methoxyestradiol (2ME2), an endogenous metabolite with low estrogen receptor affinity, has both antiangiogenic and antiproliferative activity. 2ME2 was assessed in the rat collagen- induced arthritis (CIA) model to determine if it could prevent or involute established synovitis.MethodsRats were immunized on Day 0 with collagen and randomized to a vehicle control or two 2ME2 prevention arms. In additional studies, multiple parallel treatment arms were initiated at Day 10 after arthritis onset.Results2ME2 in preventive protocols at 30 or 100 mg/kg significantly delayed the onset and reduced the severity of clinical and radiographic CIA. In established CIA, oral 2ME2 at 50 mg/kg/bid, 100 mg/kg/day, and 300 mg/kg/day reduced severity compared to vehicle controls. Efficacy of 2ME2 delivery by osmotic pumps at 60 mg/kg/day was equivalent to 300 mg/kg/day by daily gavage. The 3 oral treatment protocols all significantly reduced radiographic scores in a dose-dependent fashion, with the greatest benefit at 300 mg/kg. 2ME2 showed marked suppression of synovial gene expression of proangiogenic bFGF and VEGF, with parallel reduction of synovial blood vessels. Serum antibody levels to native type II collagen were not reduced, suggesting that 2ME2 did not influence humoral immunity.ConclusionOur results indicate that 2ME2 may represent a novel agent for the treatment of inflammatory autoimmune diseases such as RA.
- Published
- 2008
41. Identification, biological activity, and mechanism of the anti-ischemic quinolone analog
- Author
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Jong Ho Cha, Dong Jo Chang, Jongwon Lee, Min Ji Kim, Seok Ho Kim, Chan Hee Park, Hwi Young Jung, Young-Ger Suh, Kyu-Won Kim, Do Yeon Kwon, Eun J. Yoon, Sun Ha Lim, Eung Chil Choi, Hyung Tae Yeo, and Fu-Nan Li
- Subjects
Cell Survival ,Clinical Biochemistry ,Myocardial Infarction ,Pharmaceutical Science ,Pharmacology ,Models, Biological ,Biochemistry ,Brain Ischemia ,Brain ischemia ,Structure-Activity Relationship ,In vivo ,Cell Line, Tumor ,Drug Discovery ,medicine ,Animals ,Humans ,Cardioprotective Agent ,Myocardial infarction ,Molecular Biology ,Stroke ,Molecular Structure ,Cerebral infarction ,Chemistry ,Organic Chemistry ,Biological activity ,medicine.disease ,Anti-Bacterial Agents ,Rats ,Disease Models, Animal ,Mechanism of action ,Quinolines ,Molecular Medicine ,medicine.symptom - Abstract
The quinolone analog SQ-4004 has been identified as a potentially excellent anti-ischemic agent, which exhibited highly potent efficacy in reducing infarct volume size in vivo rat MCAO model (32.1% at 0.01mg/kg) and potent cardioprotective effect at myocardial infarction in vivo model (26.6% at 0.01mg/kg) while it exhibited highly reduced anti-bacterial activity. The mechanistic study revealed that the anti-ischemic activity might exert via an anti-apoptotic pathway, which implies its therapeutic uses against the ischemic cell injuries including ischemic stroke and ischemic heart disease.
- Published
- 2007
42. Design and synthesis of quinolinones as methionyl-tRNA synthetase inhibitors
- Author
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Farhana Samrin, Su-Yeon Kim, Jeewoo Lee, Sadhna Puri, Eun J. Yoon, Taehee Kang, Sunghoon Kim, Farhanullah, and Eung Chil Choi
- Subjects
Models, Molecular ,Magnetic Resonance Spectroscopy ,Methionine—tRNA ligase ,Clinical Biochemistry ,Pharmaceutical Science ,Methionine-tRNA Ligase ,Microbial Sensitivity Tests ,Quinolones ,Spectrometry, Mass, Fast Atom Bombardment ,medicine.disease_cause ,Biochemistry ,Enterococcus faecalis ,Microbiology ,Drug Discovery ,medicine ,Enzyme Inhibitors ,Molecular Biology ,Antibacterial agent ,chemistry.chemical_classification ,biology ,Organic Chemistry ,Biological activity ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Anti-Bacterial Agents ,Enzyme ,chemistry ,Enzyme inhibitor ,Staphylococcus aureus ,biology.protein ,Molecular Medicine ,Enterococcus faecium - Abstract
Five new structural analogues of substituted-1H-quinolinones (19, 20, 23, 24, and 26) have been synthesized and evaluated for Staphylococcus aureus methionyl-tRNA synthetase enzyme inhibitory activity. These compounds were also tested against pathogens of six S. aureus, two Enterococcus faecalis, and one Enterococcus faecium. Among all the synthesized quinolinones, compound 20 displayed significant inhibitory activities in the strains of E. faecalis and E. faecium.
- Published
- 2006
43. Bovine CD14 receptor produced in plants reduces severity of intramammary bacterial infection
- Author
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Max Paape, Lev G. Nemchinov, Eun J. Sohn, Dante S. Zarlenga, Douglas D. Bannerman, and Rosemarie W. Hammond
- Subjects
Transcription, Genetic ,Lipopolysaccharide ,CD14 ,Lipopolysaccharide Receptors ,Cattle Diseases ,Apoptosis ,Enzyme-Linked Immunosorbent Assay ,Transfection ,medicine.disease_cause ,Polymerase Chain Reaction ,Biochemistry ,Microbiology ,chemistry.chemical_compound ,Mammary Glands, Animal ,Immune system ,In vivo ,Consensus Sequence ,Tobacco ,Genetics ,medicine ,Animals ,Cloning, Molecular ,Molecular Biology ,Escherichia coli ,Innate immune system ,Base Sequence ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Interleukin-8 ,Bacterial Infections ,Plants, Genetically Modified ,Recombinant Proteins ,Potexvirus ,chemistry ,biology.protein ,Cattle ,Female ,Endothelium, Vascular ,Antibody ,Bacterial outer membrane ,Biotechnology - Abstract
CD14 is a high-affinity receptor protein for the complex of bacterial LPS (LPS) and LPS binding protein in animals. Binding of the soluble form of CD14 (sCD14) to LPS, found in the outer membrane of Escherichia coli and other Gram-negative bacteria, enhances host innate immune responses, reduces the severity of mastitis, and facilitates clearance and neutralization of LPS, thus protecting against an excessive immune response to LPS and development of endotoxic shock. A truncated form of sCD14, carrying a histidine residue affinity tag for purification, was incorporated into Potato virus X for transient expression in Nicotiana benthamiana plants. Western blots probed with CD14-specific antibodies demonstrated that crude plant extracts and affinity-purified samples contained immunoreactive sCD14. Biological activity of plant-derived recombinant bovine sCD14 (PrbosCD14) was demonstrated in vitro by LPS-induced apoptosis and interleukin (IL) -8 production in bovine endothelial cells, and in vivo by enhancement of LPS-induced neutrophil recruitment. Finally, in PrbosCD14-infused glands subsequently infected with E. coli, lower numbers of viable bacteria were recovered and there was an absence of clinical symptoms, demonstrating prophylactic efficacy of PrbosCD14. This is the first report of a functionally active animal receptor protein made in plants and the prophylactic use of a plant-derived protein to reduce the severity of bacterial infections in animals.
- Published
- 2006
44. Subcutaneous Veltuzumab, a Humanized Anti-CD20 Antibody, in the Treatment of Refractory Pemphigus Vulgaris
- Author
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David Allman, William A. Wegener, David M. Goldenberg, Donald E. Tsai, Christoph T. Ellebrecht, Eun J. Choi, and Aimee S. Payne
- Subjects
Adult ,medicine.medical_specialty ,Injections, Subcutaneous ,Dermatology ,Pharmacology ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Tositumomab ,Article ,chemistry.chemical_compound ,immune system diseases ,Recurrence ,Internal medicine ,medicine ,Humans ,Immunologic Factors ,education ,Adverse effect ,education.field_of_study ,business.industry ,Pemphigus vulgaris ,Remission Induction ,medicine.disease ,Veltuzumab ,Pemphigus ,Regimen ,chemistry ,Desmoglein 3 ,Retreatment ,Rituximab ,Female ,business ,medicine.drug - Abstract
IMPORTANCE B-cell depletion with the anti-CD20 antibody rituximab is highly effective for pemphigus vulgaris (PV) treatment. However,most patients experience relapse, and intravenous rituximab infusions are expensive. Therefore, cost-effective anti-CD20 therapies are desirable.OBSERVATIONS A compassionate-use investigational new drug protocol was approved to administer veltuzumab, a second-generation humanized anti-CD20 antibody, to a patient with refractory PV. Veltuzumab was administered as two 320-mg (188mg/m2) subcutaneous doses 2 weeks apart, resulting in complete remission of disease off therapy. The disease relapsed 2 years after treatment. A second cycle of subcutaneous veltuzumab, using the same dosage regimen, again induced complete remission off therapy, which remained at9 months. No serious adverse events occurred during 35 months of follow-up. Serum veltuzumab levels were 22 and 29 μg/mL 2 weeks after the first dose of each cycle, and the drug remained detectable in the serum for longer than 3 months. Relapse and response to veltuzumab generally correlated with desmoglein 3 enzyme-linked immunosorbent assay index values. Shortly after a relapse that occurred after a long-term remission, the patient demonstrated an elevated naive (CD19+CD27−) to memory (CD19+CD27+) B-cell ratio of 19.5 and transitional (CD19+CD24+CD38+) B-cell frequency of 12.5%.CONCLUSIONS AND RELEVANCE Subcutaneous veltuzumab may be a safe, effective, and more economical alternative to intravenous rituximab for PV therapy. Clinical trials of subcutaneous veltuzumab for PV are warranted.
- Published
- 2014
45. The production and characterization of anti-bovine CD14 monoclonal antibodies
- Author
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Max Paape, Neil C. Talbot, R. H. Fetterer, Douglas D. Bannerman, Eun J Sohn, and Robert R Peters
- Subjects
Lipopolysaccharide ,Swine ,Lipopolysaccharide Receptors ,Monocytes ,law.invention ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Antibody Specificity ,law ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,Mastitis, Bovine ,Mice, Inbred BALB C ,0303 health sciences ,medicine.diagnostic_test ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,Antibodies, Monoclonal ,Flow Cytometry ,3. Good health ,Blot ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Milk ,Recombinant DNA ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Cytokines ,ELISA ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Female ,monoclonal antibodies ,Rabbits ,Antibody ,CD14 ,LPS ,medicine.drug_class ,Blotting, Western ,Immunoblotting ,Enzyme-Linked Immunosorbent Assay ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Cross Reactions ,Biology ,mastitis ,Monoclonal antibody ,03 medical and health sciences ,Mammary Glands, Animal ,Western blot ,medicine ,Animals ,Horses ,030304 developmental biology ,Hybridomas ,General Veterinary ,Macrophages ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Molecular biology ,[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics ,chemistry ,Polyclonal antibodies ,biology.protein ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Cattle ,030215 immunology - Abstract
International audience; To characterize further the chemical and biological properties of bovine soluble (bos) CD14, a panel of ten murine monoclonal antibodies (mAb) reactive with recombinant (r) bosCD14 were produced. A sandwich ELISA, using murine mAb and rabbit polyclonal antibodies reactive with rbosCD14 was developed. All the mAb were reactive by ELISA with baculovirus-derived rbosCD14 and they recognized rbosCD14 (40 kDa) by western blot analysis. The mAb also identified by western blot sCD14 (53 and 58 kDa) in milk and blood and sCD14 (47 kDa) in a lysate of macrophages obtained from involuted bovine mammary gland secretions. Analysis by ELISA of whey samples after intramammary injection of lipopolysaccharide (LPS) (10 µg) revealed increased sCD14 levels between 8 to 48 h after injection. Flow cytometric analysis showed that the mAb bound to macrophages isolated from involuted mammary gland secretions and mouse macrophages but not to swine or horse monocytes. Addition of anti-rbosCD14 mAb to monocytes stimulated with LPS reduced in vitro production of TNF-$\alpha$. The anti-rbosCD14 antibodies generated in this study will be useful in studying CD14, an accessory molecule that contributes to host innate recognition of bacterial cell wall components in mammary secretions produced during mastitis.
- Published
- 2004
46. Prospective Assessment of Platelia™Aspergillus Galactomannan Antigen for the Diagnosis of Invasive Aspergillosis in Lung Transplant Recipients
- Author
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Nina Singh, Asia Obman, Janet E. Stout, Kenneth R. McCurry, Eun J. Kwak, Shimon Kusne, Shahid Husain, and Marilyn M. Wagener
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,medicine.medical_treatment ,Aspergillosis ,Gastroenterology ,Cystic fibrosis ,Immunoenzyme Techniques ,Mannans ,Galactomannan ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Lung transplantation ,False Positive Reactions ,Pharmacology (medical) ,Antigens ,Lung ,Generalized estimating equation ,Aged ,Transplantation ,Aspergillus ,biology ,business.industry ,Galactose ,Middle Aged ,medicine.disease ,biology.organism_classification ,medicine.anatomical_structure ,chemistry ,Female ,business ,Lung Transplantation - Abstract
The clinical utility of Platelia trade mark Aspergillus galactomannan antigen for the early diagnosis of invasive aspergillosis was prospectively assessed in 70 consecutive lung transplant recipients. Sera were collected twice weekly and tested for galactomannan. Invasive aspergillosis was documented in 17.1% (12/70) of the patients. Using the generalized estimating equation model, at the cutoff value of >or= 0.5, the sensitivity of the test was 30%, specificity 93% with positive and negative likelihood ratios of 4.2 and 0.75, respectively. Increasing the cutoff value to >or= 0.66 yielded a sensitivity of 30%, specificity of 95%, and positive and negative likelihood ratios of 5.5 and 0.74. A total of 14 patients had false-positive tests, including nine who had cystic fibrosis or chronic obstructive pulmonary disease. False-positive tests occurred within 3 days of transplantation in 43% (6/14) of the patients, and within 7 days in 64% (9/14). Thus, the test demonstrated excellent specificity, but a low sensitivity for the diagnosis of aspergillosis in this patient population. Patients with cystic fibrosis or chronic obstructive pulmonary disease may transiently have a positive test in the early post-transplant period.
- Published
- 2004
47. Isolation of Alkaloids from Sinomenium acutum by Centrifugal Partition Chromatography and Their Ameliorating Effects on Dexamethasone-Induced Atrophy in C2C12 Myotubes
- Author
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Eun Ju Jung, Ji Hoon Kim, Hye Mi Kim, Shuo Guo, Do Hyun Lee, Gyu Min Lim, Ahmed Shah Syed, Wondong Kim, and Chul Young Kim
- Subjects
centrifugal partition chromatography ,Sinomenium acutum ,skeletal muscle atrophy ,sinomenine ,magnoflorine ,acutumine ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Bioactivity-guided isolation was conducted using centrifugal partition chromatography (CPC) from an extract of Sinomenium acutum rhizome, which has shown promising preventive effects in a dexamethasone-induced C2C12 myotube atrophy model. CPC was operated with a solvent system of n-butanol–acetonitrile–water (10:2:8, v/v/v, containing 0.5% triethylamine) in dual mode (ascending to descending), which provided a high recovery rate (>99%) with a high resolution. Then, the preventive effects of the obtained CPC fractions were examined against dexamethasone-induced atrophy in C2C12 myotubes according to the weight ratios of the obtained fractions. The active fractions were further purified by semi-preparative HPLC that led to obtaining five alkaloids, one lignan glycoside, and one phenylpropanoid glycoside. Among these, at a concentration of 1 nM, sinomenine, magnoflorine, and acutumine could ameliorate dexamethasone-induced myotube atrophy in C2C12 myotubes by 9.3%, 13.8%, and 11.3%, respectively.
- Published
- 2023
- Full Text
- View/download PDF
48. Association of Thymidylate Synthase (TS) Gene Polymorphisms with Incidence and Prognosis of Coronary Artery Disease
- Author
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Jung Oh Kim, Chang Soo Ryu, Jeong Yong Lee, Eun Ju Ko, Yong Hyun Ha, Jung Hoon Sung, Tae Sun Hwang, In Jai Kim, and Nam Keun Kim
- Subjects
coronary artery disease ,thymidylate synthase ,3′-untranslated region ,genetic variants ,post-transcriptional regulation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Coronary artery disease (CAD) is a prevalent cardiovascular condition characterized by the accumulation of plaque within coronary arteries. While distinct features of CAD have been reported, the association between genetic factors and CAD in terms of biomarkers was insufficient. This study aimed to investigate the connection between genetic factors and CAD, focusing on the thymidylate synthase (TS) gene, a gene involved in DNA synthesis and one-carbon metabolism. TS plays a critical role in maintaining the deoxythymidine monophosphate (dTMP) pool, which is essential for DNA replication and repair. Therefore, our research targeted single nucleotide polymorphisms that could potentially impact TS gene expression and lead to dysfunction. Our findings strongly associate the TS 1100T>C and 1170A>G genotypes with CAD susceptibility. We observed that TS 1100T>C polymorphisms increased disease susceptibility in several groups, while the TS 1170A>G polymorphism displayed a decreasing trend for disease risk when interacting with clinical factors. Furthermore, our results demonstrate the potential contribution of the TS 1100/1170 haplotypes to disease susceptibility, indicating a synergistic interaction with clinical factors in disease occurrence. Based on these findings, we propose that polymorphisms in the TS gene had the possibility of clinically useful biomarkers for the prevention, prognosis, and management of CAD in the Korean population.
- Published
- 2023
- Full Text
- View/download PDF
49. Analysis of Under-Diagnosed Malignancy during Fine Needle Aspiration Cytology of Lymphadenopathies
- Author
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Jeeyong Lee, Hwa Jeong Ha, Da Yeon Kim, Jae Soo Koh, and Eun Ju Kim
- Subjects
lymphadenopathy ,fine needle aspiration cytology (FNAC) ,under-diagnosis ,malignancy ,biomarker ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Fine needle aspiration cytology (FNAC) is a useful tool in the evaluation of lymphadenopathy. It is a safe and minimally invasive procedure that provides preoperative details for subsequent treatment. It can also diagnose the majority of malignant tumors. However, there are some instances where the diagnosis of tumors remains obscure. To address this, we re-analyzed the misinterpreted patients’ samples using mRNA sequencing technology and then identified the characteristics of non-Hodgkin’s lymphoma that tend to be under-diagnosed. To decipher the involved genes and pathways, we used bioinformatic and biological analysis approaches, identifying the response to oxygen species, inositol phosphate metabolic processes, and peroxisome and PPAR pathways as possibly being involved with this type of tumor. Notably, these analyses identified FOS, ENDOG, and PRKAR2B as hub genes. cBioPortal, a multidimensional cancer genomics database, also confirmed that these genes were associated with lymphoma patients. These results thus point to candidate genes that could be used as biomarkers to minimize the false-negative rate of FNAC diagnosis. We are currently pursuing the development of a gene chip to improve the diagnosis of lymphadenopathy patients with the ultimate goal of improving their prognosis.
- Published
- 2023
- Full Text
- View/download PDF
50. Increased Levels of LPS-Binding Protein in Bovine Blood and Milk Following Bacterial Lipopolysaccharide Challenge
- Author
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William R. Hare, M.J. Paape, Eun J Sohn, and Douglas D. Bannerman
- Subjects
Lipopolysaccharides ,medicine.medical_specialty ,Gram-negative bacteria ,Lipopolysaccharide ,Neutrophils ,CD14 ,Lipopolysaccharide Receptors ,Microbiology ,Leukocyte Count ,chemistry.chemical_compound ,Mammary Glands, Animal ,Internal medicine ,Lactation ,Escherichia coli ,Genetics ,medicine ,Animals ,Mastitis, Bovine ,Toll-like receptor ,Membrane Glycoproteins ,biology ,Interleukin-8 ,Acute-phase protein ,biology.organism_classification ,Kinetics ,Milk ,medicine.anatomical_structure ,Endocrinology ,chemistry ,biology.protein ,Cattle ,Female ,lipids (amino acids, peptides, and proteins) ,Animal Science and Zoology ,Carrier Proteins ,Bacterial outer membrane ,Lipopolysaccharide binding protein ,Acute-Phase Proteins ,Food Science - Abstract
Several species of gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae, and various species of Enterobacter, are common mastitis pathogens. All of these bacteria are characterized by the presence of endotoxin or lipopolysaccharide (LPS) in their outer membrane. The bovine mammary gland is highly sensitive to LPS, and LPS has been implicated, in part, in the pathogenesis of gram-negative mastitis. Recognition of LPS is a key event in the innate immune response to gram-negative infection and is mediated by the accessory molecules CD14 and LPS-binding protein (LBP). The objective of the current study was to determine whether LBP levels increased in the blood and mammary gland following LPS challenge. The left and right quarters of five midlactating Holstein cows were challenged with either saline or LPS (100 microg), respectively, and milk and blood samples collected. Basal levels of plasma and milk LBP were 38 and 6 microg/ml, respectively. Plasma LBP levels increased as early as 8 h post-LPS challenge and reached maximal levels of 138 microg/ ml by 24 h. Analysis of whey samples derived from LPS-treated quarters revealed an increase in milk LBP by 12 h. Similar to plasma, maximal levels of milk LBP (34 microg/ml) were detected 24 h following the initial LPS challenge. Increments in milk LBP levels paralleled a rise in soluble CD14 (sCD14) levels and initial rises in the levels of these proteins were temporally coincident with maximal neutrophil recruitment to the inflamed gland. Because LBP and sCD14 are known to enhance LPS-induced host cell activation and to facilitate detoxification of LPS, these data are consistent with a role for these molecules in mediating mammary gland responses to LPS.
- Published
- 2003
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