3,390 results on '"Jeong MJ"'
Search Results
2. PET Quantification in Healthy Humans of Cyclooxygenase-2, a Potential Biomarker of Neuroinflammation.
- Author
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Yan X, Noergaard M, Morse CL, Liow JS, Hong J, Greve D, Telu S, Kim MJ, Montero Santamaria JA, Galassi A, Feng N, Williams Avram SK, Usdin TB, Wu S, Zhang A, Manly LS, Jenkins M, Van Buskirk M, Lee A, Zoghbi SS, Pike VW, Zanotti-Fregonara P, and Innis RB
- Abstract
Cyclooxygenase-2 (COX-2) is present in a healthy brain at low densities but can be markedly upregulated by excitatory input and by inflammogens. This study evaluated the sensitivity of the PET radioligand [
11 C]-6-methoxy-2-(4-(methylsulfonyl)phenyl)- N -(thiophen-2-ylmethyl)pyrimidin-4-amine ([11 C]MC1) to detect COX-2 density in a healthy human brain. Methods: The specificity of [11 C]MC1 was confirmed using lipopolysaccharide-injected rats and transgenic mice expressing the human COX-2 gene, with 120-min baseline and blocked scans using COX-1 and COX-2 selective agents. Twenty-seven healthy participants were injected with [11 C]MC1. Ten of these participants received 2 PET scans: a baseline study followed by blockade with celecoxib (600 mg orally), a preferential COX-2 inhibitor. Seventeen participants underwent test-retest imaging. All scans included concurrent arterial sampling. The tissue-to-plasma ratio at equilibrium (i.e., total distribution volume) was determined using a 2-tissue compartment model (2TCM). Results: In humanized transgenic COX-2 mice, 70%-90% of [11 C]MC1 brain uptake was blocked by nonradioactive MC1 and celecoxib (a COX-2 selective inhibitor) but not by PS13 (a COX-1 selective inhibitor), thereby confirming specific binding to human COX-2. Radioactivity in the human brain peaked at a concentration of about 4.0 SUV, indicating good passage through the blood-brain barrier. Values for the total distribution volume achieved stability after 80 min, indicating no radiometabolite contamination. Celecoxib reduced radioligand binding in neocortical areas by 25% but had little or no effect in subcortical regions and the cerebellum, which correlated with COX-2 messenger RNA expression levels. Binding site occupancy by celecoxib was virtually complete, as determined by the Lassen plots. Test-retest reliability was moderate (intraclass correlation coefficient, 0.65) but had relatively large variability (absolute retest variability, 20%). Reference tissue methods yielded results comparable to those of 2TCM but reduced retest variability by up to 75% and reduced intersubject variability (coefficient of variation) by about half. Thus, compared with 2TCM, which requires arterial blood, the reference tissue method is expected to significantly reduce the sample sizes required to detect statistically significant differences between groups. Conclusion: [11 C]MC1 has adequate sensitivity to measure the low density of COX-2 in a healthy human brain, suggesting it can also quantify the COX-2 elevations expected in human disorders associated with neuroinflammation., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2025
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3. Assessing seepage sources of a tailings dump and fractionation of Mo and Zn isotopes.
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Kim DM, Im DG, Kwon HL, Yun ST, Lee KR, Park MJ, and Park MS
- Abstract
Tracing the sources of each contaminant and its geochemical reactions requires a variety of geochemical tools. In this study, chemical compositions and isotopic ratios of O-H, Mo, and Zn were utilized to identify the sources and geochemical reactions of water, As, Mo, and Zn in the seepage from a mine tailings dump. The distinct chemical compositions observed between the seepage and monitoring well, along with the O-H isotopic ratios, suggested that the seepage originated from creek water rather than nearby groundwater, which was supported by a large seasonal variation of δ
98 Mo in both the seepage and creek. Interpretation results indicated that Mo was predominantly supplied from the creek, while the majority of As and Zn originated from the tailings. During the transport of Mo and Zn, δ98 Mo and δ66 Zn increased and decreased, respectively, suggesting adsorptive removal, despite the δ66 Zn increase during the leaching of the tailings. Notably, the combined use of Mo and Zn isotopic ratios proved to be a valuable tool for identifying geochemical reactions and determining sources and pathways in complex environmental systems. Additionally, although As does not have multiple isotopes, possible adsorption of As onto Fe (oxy)hydroxides could be inferred based on the isotopic behavior of Mo and Zn, as these two isotopes effectively reflected isotopic fractionation during adsorption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)- Published
- 2025
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4. Advancements in Frank's sign Identification using deep learning on 3D brain MRI.
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Jo S, Kim JS, Kwon MJ, Park J, Kim JL, Jhoo JH, Kim E, Sunwoo L, Kim JH, Han JW, and Kim KW
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- Humans, Female, Male, ROC Curve, Middle Aged, Adult, Aged, Deep Learning, Magnetic Resonance Imaging methods, Imaging, Three-Dimensional methods, Brain diagnostic imaging
- Abstract
Frank's sign (FS) is a diagnostic marker associated with aging and various health conditions. Despite its clinical significance, there lacks a standardized method for its identification. This study aimed to develop a deep learning model for automated FS detection in 3D facial images derived from MRI scans. Four deep learning architectures were evaluated for FS segmentation on a dataset of 400 brain MRI scans. The optimal model was subsequently validated on two external datasets, comprising 300 brain MRI scans each with varying FS presence. Dice similarity coefficient (DSC) and receiver operating characteristic (ROC) analysis were employed to assess model performance. The U-net architecture demonstrated superior performance in terms of accuracy and efficiency. On the validation datasets, the model achieved a DSC of 0.734, an intra-class correlation coefficient of 0.865, and an area under the ROC curve greater than 0.9 for FS detection. Additionally, the model identified optimal voxel thresholds for accurate FS classification, resulting in high sensitivity, specificity, and accuracy metrics. This study successfully developed a deep learning model for automated FS segmentation in MRI scans. This tool has the potential to enhance FS identification in clinical practice and contribute to further research on FS and its associated health implications., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)
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- 2025
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5. Tear film lipid layer thickness and blink dynamics in patients with blepharospasm.
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Paik JS, Kwon MJ, Nam GH, Han K, Whang WJ, Hwang HS, Yang SW, Kim HS, Na KS, and Cho WK
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- Humans, Female, Male, Aged, Middle Aged, Retrospective Studies, Lipids, Neuromuscular Agents therapeutic use, Neuromuscular Agents administration & dosage, Interferometry, Aged, 80 and over, Blepharospasm physiopathology, Blepharospasm drug therapy, Tears metabolism, Blinking physiology, Dry Eye Syndromes physiopathology, Dry Eye Syndromes drug therapy, Dry Eye Syndromes metabolism, Botulinum Toxins, Type A therapeutic use, Botulinum Toxins, Type A administration & dosage
- Abstract
Background: This study investigates the effect of botulinum toxin A on lipid layer thickness (LLT) and blink dynamics in patients with benign essential blepharospasm (BEB) compared to dry eye disease (DED) patients., Methods: We reviewed the medical records of patients with dry eye disease (DED) and BEB treated with botulinum toxin A (BoT A) injections. Data on demographics, lipid layer thickness (LLT), meiboscore, and blink dynamics measured using a LipiView II interferometer before and 2 months after BoT A were collected., Results: Each 28 eyes from 28 patients with BEB and age- and sex-matched patients with DED were included. When comparing blink dynamics, complete blink rate was significantly higher in the pre-injection BEB group compared to the DED group (5.25 ± 4.32 times/20 s vs. 2.43 ± 2.82 times/20 s, p = 0.0055). In tear film lipid profiles analyzed in BEB patients at pre-injection and 2-month follow-up after injection, average LLT significantly increased after injection (72.4 ± 22.7 nm to 83.0 ± 22.2 nm, p = 0.0215). Diabetes and young age were associated factors influencing the LLT increase. Significant increase in LLT was observed post-injection, with specific demographic factors, including diabetes and age, associated with this improvement. Additionally, blink dynamics showed a decrease in complete blink rate post-injection., Conclusions: These findings suggest that BoT-A may alleviate BEB symptoms, but ophthalmologists should carefully interpret LLT and blink patterns in BEB patients due to potential overestimations of blink efficacy by the interferometer., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board (IRB) of Yeouido St. Mary’s Hospital, The Catholic University of Korea (SC22RISI0088) and conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. The IRB waived the requirement for obtaining informed consent from participants due to the retrospective nature of the chart review in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)
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- 2025
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6. Ultrafast Synthesis of Hard Carbon Anodes for Sodium-ion Batteries: An Intense-Pulsed-Light-Assisted Approach to Photothermal Carbonization of Polymer/Carbon Nanotube Composite Films.
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Ryoo G, Kim MJ, Kim MS, Shin S, Lee JW, Kim BG, Lee DG, Kim Y, Seo H, Cho JY, Han JT, Jeong SY, Kim J, Lee DY, Jeong HJ, and Park JH
- Abstract
The conventional carbonization process for synthesizing hard carbons (HCs) requires high-temperature furnace operations exceeding 1000 °C, leading to excessive energy consumption and lengthy processing times, which necessitates the exploration of more efficient synthesis methods. This study demonstrates the rapid preparation of HC anodes using intense pulsed light (IPL)-assisted photothermal carbonization without the prolonged and complex operations typical of traditional carbonization methods. A composite film of microcrystalline cellulose (MCC) and single-walled carbon nanotubes (SWCNTs) is carbonized at high temperatures in less than 1 min. The SWCNTs efficiently absorbed light energy, enabling ultrafast heating and eliminating the need for prolonged, high-energy furnace-based processes. The IPL-assisted HC anodes exhibited excellent electrochemical performance, with an initial desodiation capacity of 260.4 mAh g⁻¹
anode and 97.5% capacity retention after 200 cycles. These results are comparable to those achieved using traditional furnace-based carbonization processes, such as carbonizing HC anodes at 1200 °C, validating the effectiveness of IPL-assisted processes. Additionally, surface and structural analyses revealed the development of pseudo-graphitic domains, crucial for enhanced sodium-ion storage. This research highlights IPL-assisted photothermal carbonization as a viable, time-efficient, and energy-saving alternative to conventional methods, offering a sustainable pathway for the large-scale production of HC anodes for future sodium-ion battery technologies., (© 2025 Wiley‐VCH GmbH.)- Published
- 2025
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7. Heavy metal exposure and its effects on APOC3, CFAI, and ZA2G.
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Kim NE, Heo M, Shin H, Do AR, Kim J, Kang HG, Mun S, Yoo HJ, Kim MJ, Kim JW, Kim CH, Hong YS, Cho YM, Jin H, Park K, Kim WJ, and Won S
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Biomarkers blood, Biomarkers urine, Environmental Exposure adverse effects, Apolipoprotein C-III genetics, Apolipoprotein C-III blood, Metals, Heavy toxicity, Metals, Heavy urine, Metals, Heavy blood
- Abstract
Despite increasing heavy metal pollution, traditional epidemiology often fails to link exposure to health outcomes. This study used multi-omics to investigate associations between heavy metal exposure and health. Blood and urine samples from 294 participants in heavy metal-exposed and control areas were analyzed, revealing key biomarkers. Meta P analysis revealed consistent trends in apolipoprotein C3 (APOC3) expression, and mediation analysis showed significant effects of APOC3 and zinc-alpha-2-glycoprotein (ZA2G) on metabolites: the mediating effect of APOC3 from blood cadmium to serotonin was 0.023 (P < 0.001) and that to 3-phosphoglyceric acid (3PG) was 0.0125 (P = 0.002). Mendelian randomization confirmed the positive impact of APOC3 and Complement Factor I (CFAI) and the negative effect of ZA2G on metabolites, with apolipoprotein H (APOH) methylation significantly altering APOC3 (β = -0.22, P = 0.017), CFAI (β = 0.176, P = 0.035), and ZA2G (β = 0.139, P = 0.048) protein levels. Liver function variables, including albumin, total protein, calcium, and lactate dehydrogenase, correlated with 3PG and serotonin levels in the exposed areas. Sex-specific analysis showed that men exhibited stronger compensatory mechanisms via CFAI and myo-inositol, while women's greater vulnerability to heavy metal exposure highlighted the need for targeted interventions. These findings suggest APOH methylation affects APOC3, CFAI, and ZA2G levels, elevating 3PG, inosine monophosphate, and serotonin levels and harming liver function via lipolysis, supporting the use of these markers in health monitoring, therapies, and policies to limit heavy metal risks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2025
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8. Continuous single-ended depth-of-interaction measurement using highly multiplexed signals and artificial neural networks.
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Shim HS, Cho MJ, Lee MS, and Lee JS
- Abstract
Objective: This study aims to enhance positron emission tomography (PET) imaging systems by developing a continuous depth-of-interaction (DOI) measurement technique using a single-ended readout. Our primary focus is on reducing the number of readout channels in the scintillation detectors while maintaining accurate DOI estimations, using a high-pass filter-based signal multiplexing technique combined with artificial neural networks (ANNs).
Approach: Instead of reading out all 64 signals from an 8×8 silicon photomultiplier array for DOI estimation, the proposed method technique reduces the signals into just four channels by applying high-pass filters with different time constants. To recover the original signal amplitudes, an ANN is used to demultiplex the multiplexed signals. Specifically, the ANN processes the sampled waveforms of these four multiplexed signals and estimates the energy information of the original 8×8 SiPM channels. In this study, two DOI estimation strategies were explored for a continuous DOI PET detector utilizing triangular teeth-shaped reflectors: a 'single-step estimation' method directly estimating DOI from multiplexed signals, and a 'two-stage cascade estimation' method that first demultiplexes the signals and then estimates DOI. The performances of proposed strategies were validated using data irradiated at five steps (2 mm, 6 mm, 10 mm, 14 mm, and 18 mm).
Results: The signal amplitude of row/column summed signals, which were recovered using the proposed ANN-based demultiplexing, showed strong correlation with ground truth (e.g., R2=0.98 for 125 MHz digitizer sampling rate). Moreover, both the single-step and two-stage estimation methods achieved high accuracy in DOI estimation, with an average DOI estimation accuracy of 72.9% and 74.0% at 125 MHz sampling rate when considering an error range of ± 1 DOI position. 
Significance: This novel signal multiplexing technique significantly reduces the number of required readout channels, making continuous DOI PET more cost-effective. 
., (© 2025 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)
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- 2025
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9. Block Copolymer Electrolytes with Double Primitive Cubic Structures: Enhancing Solid-State Lithium Conduction via Lithium Salt Localization.
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Lee H, Kim J, and Park MJ
- Abstract
We present a strategy for enhancing Li
+ conduction in block copolymer electrolytes by introducing trace amounts of Li salts into polystyrene- b -poly(ethylene oxide) (PS- b -PEO), wherein Li+ ions preferentially coordinate with the -OH end groups of the PEO chains, resulting in the formation of double primitive cubic ( Im 3̅ m ) structures. Compared with TFSI- anions in Li salts, smaller anions (PF6 - and BF4 - ) could facilitate ion localization more effectively, expanding the salt concentration range for developing stable Im 3̅ m structures. The Im 3̅ m structures formed in PS- b -PEOs doped with LiBF4 at r = 0.013-0.02 ( r ≡ [Li+ ]/[EO]) exhibited ionic conductivities several times higher than those doped at the conventional level (e.g., r = 0.06). The corresponding morphology factors were more than eight times higher than those of the lamellar-forming electrolytes. Notably, the activation energy value for Li+ conduction in PS- b -PEO with one Li+ ion per entire PEO chain was only 0.012 eV (by Vogel-Fulcher-Tammann), indicating that Li+ transport was less dependent on polymer relaxation. Furthermore, modifying the PEO chain ends with three -PO3 H2 groups further strengthened the Li+ -mediated end-end interactions and significantly extended the salt concentration range to form Im 3̅ m structures. In contrast, increasing the number of -OH end groups (such as diols and triols) had minimal effect on stabilizing the network morphologies.- Published
- 2025
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10. Effect of Combining Exercise with Adipose-Derived Mesenchymal Stem Cells in Muscle Atrophy Model of Sarcopenia.
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Jeong DH, Kim MJ, and Park CH
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- Animals, Rats, Male, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, AMP-Activated Protein Kinases metabolism, Rats, Sprague-Dawley, Sarcopenia therapy, Sarcopenia pathology, Sarcopenia metabolism, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells cytology, Physical Conditioning, Animal, Mesenchymal Stem Cell Transplantation methods, Muscular Atrophy therapy, Muscular Atrophy pathology, Muscular Atrophy metabolism, Muscular Atrophy etiology, Disease Models, Animal, Adipose Tissue cytology
- Abstract
Deterioration in muscle mass, strength, and physical performance due to conditions such as sarcopenia can affect daily activities and quality of life in the elderly. Exercise and mesenchymal stem cells (MSCs) are potential therapies for sarcopenia. This study evaluates the combined effects of exercise and adipose-derived MSCs (ADMSCs) in aged rats with sarcopenia. Eighteen-month-old rats were randomly divided into four groups: control, exercise (Ex), ADMSCs injection (MSC), and ADMSCs injection with exercise (MSC + Ex). Gastrocnemius (GCM) muscle mass increased in the Ex, MSC, and MSC + Ex groups compared to the control group. Although the mean CSA did not differ significantly between the groups, the size distribution of myofibers shifted toward larger sizes in the Ex and MSC + Ex groups. The MSC + Ex group performed best in functional tests, including the rotarod and hot plate tests. The protein expression levels of tumor necrosis factor (TNF) and the p-AMP-activated protein kinase (AMPK)/AMPK ratio in the GCM muscle were the lowest in the MSC + Ex group. This study demonstrates that combining exercise and ADMSC interventions was the most effective treatment for aged sarcopenic rats, suggesting a potential synergistic approach for sarcopenia treatment.
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- 2025
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11. Highly accurate Korean draft genomes reveal structural variation highlighting human telomere evolution.
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Kim J, Park JL, Yang JO, Kim S, Joe S, Park G, Hwang T, Cho MJ, Lee S, Lee JE, Park JH, Yeo MK, and Kim SY
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- Humans, DNA Repair genetics, Genomic Structural Variation, Genomics methods, Republic of Korea, East Asian People genetics, Evolution, Molecular, Genome, Human genetics, Telomere genetics
- Abstract
Given the presence of highly repetitive genomic regions such as subtelomeric regions, understanding human genomic evolution remains challenging. Recently, long-read sequencing technology has facilitated the identification of complex genetic variants, including structural variants (SVs), at the single-nucleotide level. Here, we resolved SVs and their underlying DNA damage-repair mechanisms in subtelomeric regions, which are among the most uncharted genomic regions. We generated ∼20 × high-fidelity long-read sequencing data from three Korean individuals and their partially phased high-quality de novo genome assemblies (contig N50: 6.3-58.2 Mb). We identified 131 138 deletion and 121 461 insertion SVs, 41.6% of which were prevalent in the East Asian population. The commonality of the SVs identified among the Korean population was examined by short-read sequencing data from 103 Korean individuals, providing the first comprehensive SV set representing the population based on the long-read assemblies. Manual investigation of 19 large subtelomeric SVs (≥5 kb) and their associated repair signatures revealed the potential repair mechanisms leading to the formation of these SVs. Our study provides mechanistic insight into human telomere evolution and can facilitate our understanding of human SV formation., (© The Author(s) 2025. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2025
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12. Correction: c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer.
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Park J, Chang ES, Kim JY, Chelakkot C, Sung M, Song JY, Jung K, Lee JH, Choi JY, Kim NY, Lee H, Kang MR, Kwon MJ, Shin YK, Park YH, and Choi YL
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- 2025
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13. GPR40-full agonist AM1638 alleviates palmitate-induced oxidative damage in H9c2 cells via an AMPK-dependent pathway.
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Yun S, Kim JW, Park MJ, Song E, Jang SY, Jang A, Choi KM, Baik SH, Hwang HJ, and Yoo HJ
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G protein-coupled receptor 40 (GPR40) is gaining recognition as a potential therapeutic target for several metabolic disturbances, such as hyperglycemia and excessive inflammation. GPR40 is expressed in various tissues, including the heart; however, its specific roles in cardiomyocytes remain unknown. The objective of the present study was to investigate whether treatment with AM1638, a GPR40-full agonist, reduces palmitate-mediated cell damage in H9c2 rat cardiomyocytes. AM1638 treatment increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and expression levels of the antioxidant molecules heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase-1 (NQO1). Palmitate-mediated superoxide production and levels of 4-hydroxynonenal, a biomarker of oxidative stress, decreased after treatment with AM1638. Notably, palmitate-mediated disruption of mitochondrial membrane potential, lower levels of mitochondrial complex protein, and failure of adenosine triphosphate production were all recovered by treatment with AM1638. Moreover, AM1638 blocked palmitate-mediated caspase-3 cleavage and nuclear fragmentation, thereby improving cell viability. However, these AM1638-mediated beneficial effects were abrogated by treatment with Compound C, an AMPK inhibitor. These results demonstrate that AM1638, a GPR40-full agonist, ameliorates palmitate-mediated oxidative stress in H9c2 cells in an AMPK-dependent manner.
- Published
- 2025
14. ASO Visual Abstract: Preventing Breast Cancer-Related Lymphedema-A Comprehensive Analysis of a 9-Year Single-Center Experience of Prophylactic Lymphovenous Bypass.
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Cho MJ, Senger JL, Park KU, Hansotia K, Chratian S, Kadle R, and Skoracki R
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Competing Interests: DISCLOSURE: The authors have no financial disclosures or conflicts of interest.
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- 2025
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15. Gastric Microbiota Associated with Gastric Precancerous Lesions in Helicobacter pylori -Negative Patients.
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Kim HN, Kim MJ, Jacobs JP, and Yang HJ
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Studies on the gastric microbiota associated with gastric precancerous lesions remain limited. This study aimed to profile the gastric mucosal microbiota in patients with Helicobacter pylori -negative precancerous lesions. Gastric mucosal samples were obtained from 67 H. pylori -negative patients, including those with chronic gastritis (CG), intestinal metaplasia (IM), and dysplasia. The V3-V4 region of the 16S rRNA gene was sequenced and analyzed. No significant difference was observed in the alpha or beta diversity of the gastric microbiota among the groups. However, a taxonomic analysis revealed a significant enrichment of Lautropia mirabilis and the depletion of Limosilactobacillus reuteri , Solobacxterium moorei , Haemophilus haemolyticus , and Duncaniella dubosii in the IM and dysplasia groups compared to those in the CG group. Prevotella jejuni and the genus Parvimonas were enriched in the IM group. A predictive functional analysis revealed enrichment of the ornithine degradation pathway in the IM and dysplasia groups, suggesting its role in persistent gastric mucosal inflammation associated with gastric precancerous lesions. The gastric microbiota associated with H. pylori -negative gastric precancerous lesions showed an increased abundance of oral microbes linked to gastric cancer and a reduction in anti-inflammatory bacteria. These alterations might contribute to chronic gastric mucosal inflammation, promoting carcinogenesis in the absence of H. pylori infection.
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- 2025
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16. [ 11 C]PS13 Demonstrates Pharmacologically Selective and Substantial Binding to Cyclooxygenase-1 in the Human Brain.
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Ghazanfari N, Liow JS, Kim MJ, Cureton R, Lee A, Knoer C, Jenkins M, Hong J, Santamaria JAM, Shetty HU, Galassi A, Wighton P, Nørgaard M, Greve DN, Zoghbi SS, Pike VW, Innis RB, and Zanotti-Fregonara P
- Subjects
- Humans, Male, Adult, Female, Ketoprofen pharmacokinetics, Ketoprofen metabolism, Protein Binding, Carbon Radioisotopes, Radiopharmaceuticals pharmacokinetics, Young Adult, Tissue Distribution, Cyclooxygenase 1 metabolism, Brain diagnostic imaging, Brain metabolism, Positron-Emission Tomography
- Abstract
Our laboratory recently developed [
11 C]PS13 as a PET radioligand to selectively measure cyclooxygenase-1 (COX-1). The cyclooxygenase enzyme family converts arachidonic acid into prostaglandins and thromboxanes, which mediate inflammation. The total brain uptake of [11 C]PS13, which is composed of both specific binding and background uptake, can be accurately quantified with gold standard methods of compartmental modeling. This study sought to quantify the specific binding of [11 C]PS13 to COX-1 in healthy human brain using scans performed with arterial input function at baseline and after blockade by the COX-1-selective inhibitor ketoprofen. Methods: Eight healthy volunteers underwent two 90-min [11 C]PS13 PET scans with radiometabolite-corrected arterial input function, at baseline and about 2 h after oral administration of ketoprofen (75 mg). Results: Two-tissue compartment modeling effectively identified the total uptake of radioactivity in the brain (as distribution volume), showing the highest densities in the hippocampus, the occipital cortex, and the banks of the central sulcus. All brain regions exhibited displaceable and specific binding, and thus none could be used as a reference region. Ketoprofen blocked approximately 84% of the binding sites on COX-1 in the whole brain. After full occupancy was extrapolated, the average whole-brain values of [11 C]PS13 were 1.6 ± 0.8 mL·cm-3 for specific uptake, 1.7 ± 0.6 mL·cm-3 for background uptake, and 1.1 ± 0.5 for the specific-to-background ratio. The hippocampus had the highest specific-to-background ratio value of 2.7 ± 0.9. Conclusion: [11 C]PS13 exhibited high specific binding to COX-1 in the human brain, but its quantification requires arterial blood sampling., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2025
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17. eIF2α phosphorylation-ATF4 axis-mediated transcriptional reprogramming mitigates mitochondrial impairment during ER stress.
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Le HT, Yu J, Ahn HS, Kim MJ, Chae IG, Cho HN, Kim J, Park HK, Kwon HN, Chae HJ, Kang BH, Seo JK, Kim K, and Back SH
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Eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, which regulates all 3 unfolded protein response pathways, helps maintain cellular homeostasis and overcome endoplasmic reticulum (ER) stress through transcriptional and translational reprogramming. However, transcriptional regulation of mitochondrial homeostasis by eIF2α phosphorylation during ER stress is not fully understood. Here, we report that the eIF2α phosphorylation-activating transcription factor 4 (ATF4) axis is required for the expression of multiple transcription factors, including nuclear factor erythroid 2-related factor 2 and its target genes responsible for mitochondrial homeostasis during ER stress. eIF2α phosphorylation-deficient (A/A) cells displayed dysregulated mitochondrial dynamics and mitochondrial DNA replication, decreased expression of oxidative phosphorylation complex proteins, and impaired mitochondrial functions during ER stress. ATF4 overexpression suppressed impairment of mitochondrial homeostasis in A/A cells during ER stress by promoting the expression of downstream transcription factors and their target genes. Our findings underscore the importance of the eIF2α phosphorylation-ATF4 axis for maintaining mitochondrial homeostasis through transcriptional reprogramming during ER stress., Competing Interests: DECLARATION OF COMPETING INTERESTS The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2025
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18. Co-occurrence patterns between Chlorophyta and nucleocytoplasmic large DNA virus in coastal ecosystem, South Korea.
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Kim MJ, Kim KE, Kim HJ, Kim YJ, Lee TK, Kim SM, Cha HG, and Jung SW
- Abstract
Nucleocytoplasmic large DNA viruses (NCLDVs) are known to infect phytoplankton and play a significant role in regulating their population dynamics. In this study, we aimed to investigate the co-occurrence patterns between phytoplankton and NCLDVs in the southern coastal ecosystem of South Korea. We collected seawater every month from March 2018 to December 2020 and analyzed the samples using Cytochrome c Oxidase subunit I metabarcoding and metagenomic analyses. Chlorophyta (36.08%) was the most abundant eukaryotic taxon, with Bathycoccaceae (58.25%) and Mamiellaceae (41.51%) being the most dominant families within Chlorophyta. Bathycoccaceae was dominant in winter, whereas Mamiellaceae was dominant in summer. In the NCLDV community, Phycodnaviridae (75.12%) was found to be the major family. The co-occurrence pattern of Phycodnaviridae showed a high correlation with Bathycoccaceae and Mamiellaceae, which is explained by the "boom-and-bust" concept. In particular, we predicted co-occurrence patterns between Bathycoccus prasinos and Prasnovirus, with known infectious relationships, and confirmed co-occurrence patterns between B. prasinos and Coccolithovirus and Micromonas pusilla and Prymnesiovirus, with unknown infectious relationships. These co-occurrence patterns between Chlorophyta and Phycodnaviridae provide valuable insights into the control of pico-sized primary production and the microbial loop of the coastal ecosystem., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)
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- 2025
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19. Transferrin-binding domain inserted-adenovirus hexon engineering enables systemic immune evasion and intratumoral T-cell activation.
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Lee DH, Kwon Y, Um KH, Yoo JK, Ha W, Kim KS, Cha J, Cho HE, Park KS, Kye MJ, and Choi JW
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- Animals, Humans, Mice, Immune Evasion, Oncolytic Virotherapy methods, Genetic Vectors genetics, Genetic Vectors immunology, Cell Line, Tumor, Lymphocyte Activation immunology, CD8-Positive T-Lymphocytes immunology, Transferrin metabolism, Oncolytic Viruses immunology, Oncolytic Viruses genetics, Neisseria meningitidis immunology, Neisseria meningitidis genetics, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Female, Adenoviridae immunology, Adenoviridae genetics, Capsid Proteins immunology, Capsid Proteins genetics
- Abstract
Rationale: Adenovirus-based therapies have encountered significant challenges due to host immunity, particularly from pre-existing antibodies. Many trials have struggled to evade antibody response; however, the efficiency of these efforts was limited by the diversity of antibody Fv-region recognizing multiple amino acid sequences. Methods: In this study, we developed an antibody-evading adenovirus vector by encoding a plasma-rich protein transferrin-binding domain. The coding sequence was employed from Neisseria Meningitides and inserted in the experimentally-optimized site within the adenovirus capsid protein. Result: This engineered antibody-evading oncolytic adenovirus overcame the reduction in productivity and infectivity typically caused by the insertion of a foreign domain. We observed decreased immune recognition and compromised formation of anti-adenovirus antibodies. Furthermore, the anti-tumor efficacy was demonstrated both in vitro and in vivo , with increased recruitment of CD8
+ T cells. Conclusion: This novel antibody-evading strategy effectively evades neutralizing antibodies and innate immunity while boosting cytotoxic immunity by recruiting CD8+ T cells at the tumor site. Additionally, this strategy holds potential for application in other gene therapies and adenovirus vectors., Competing Interests: Competing Interests: D. H. L., Y. K., K. H. U., J. K. Y., W. H., K. K., and M. J. K. partially received research grants from Curigin. Ltd. J. C., H. C., K. S. P., and J. W. C. declares no competing interests associated with this manuscript., (© The author(s).)- Published
- 2025
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20. Plant P450 forms indigo and indirubin when expressed in Escherichia coli.
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Sagwan-Barkdoll L, Kim MJ, Berim A, Gang DR, and Anterola AM
- Subjects
- Molecular Structure, Indoles metabolism, Indoles chemistry, Escherichia coli genetics, Escherichia coli metabolism, Cytochrome P-450 Enzyme System metabolism, Cytochrome P-450 Enzyme System genetics, Indigo Carmine metabolism, Isatis metabolism, Isatis chemistry, Isatis genetics, Isatis enzymology
- Abstract
Indigo and indirubin are derived from indoxyl molecules, which generally occur as indoxyl glycosides in woad (Isatis tinctoria L.) and other indigo-producing plants. Indoxyl glycosides are biosynthesized from indole via 3-hydroxylation to form indoxyl, followed by one or more glycosylations. Enzymes that attach and remove sugars to and from indoxyl have already been isolated and characterized, while enzymes that convert indole into indoxyl in plants have remained elusive, until the identification of P450s and flavin-containing monooxygenases that hydroxylate indole. A P450 gene from woad (named CYP71B102) was heterologously expressed in E. coli, resulting in the formation of indigo and indirubin, as well as isatin and 2-oxindole, which along with indoxyl are putative precursors of indirubin. The addition of either isatin or 2-oxindole to the recombinant E. coli reduced the levels of indigo and increased the amount of indirubin, whereas coexpression of CYP71B102 with isatin hydroxylase (which degrades isatin) increased the levels of indigo and decreased the amount of indirubin, albeit slightly. The results suggest that CYP71B102 hydroxylates indole at both the 2- and 3- positions to produce 2-oxindole and indoxyl, respectively, and that the coupling of indoxyl with either 2-oxindole or isatin forms indirubin, while dimerization of indoxyl forms indigo. This P450 gene is thus likely involved in the biosynthesis of indirubin in woad, as well as the formation of indigo and its glycosidic precursors, even if other types of enzymes, such as flavin-containing monooxygenases, may be involved in indole hydroxylation in other indigo-producing plants., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aldwin M. Anterola reports financial support was provided by Fred C Gloeckner Foundation Inc. Aldwin M. Anterola reports funding was provided by Blueline Biotech LLC. Aldwin M. Anterola reports a relationship with Blueline Biotech LLC that includes: equity or stocks. Aldwin M. Anterola has patent Indole-derived compound production issued to Board of Trustees of Southern Illinois University. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)
- Published
- 2025
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21. Increasing trends of laparoscopic procedures in non-obstetric surgery during pregnancy over 17 years at a single center: Retrospective case-control study.
- Author
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Na ED, Roh M, Lim SJ, Kwak MJ, Kim H, Baek MJ, Ahn EH, Jung SH, and Jang JH
- Subjects
- Humans, Female, Pregnancy, Retrospective Studies, Adult, Case-Control Studies, Pregnancy Trimesters, Young Adult, Laparoscopy statistics & numerical data, Laparoscopy methods, Laparoscopy trends, Pregnancy Complications surgery, Pregnancy Complications epidemiology
- Abstract
Objective: This study aimed to examine the diseases requiring surgery during pregnancy, the changes in surgical methods over time, and the characteristics of surgeries performed in different trimesters., Methods and Materials: A retrospective study conducted at Bundang CHA Hospital between 2006 and 2023 analyzed surgeries performed during pregnancy and compared laparoscopic and open approaches across the three trimesters of pregnancy. Additionally, general (appendicitis, cholecystitis) and gynecologic (heterotopic pregnancy, adnexal torsion) cases were compared., Results: Among 36 181 delivery patients, 101 (0.28%) underwent surgery. The most common conditions were appendicitis (44.6%), cholecystitis (1.9%), heterotopic pregnancy (23.8%), adnexal torsion (27.7%), and cancer (1.9%). The laparoscopic group had a shorter operative time (41.5 ± 19.3 vs. 57.9 ± 33.9 min, p = 0.009) and hospital stay (4.9 ± 2.7 vs. 9.0 ± 9.8 days, p = 0.016) than open surgery group. Heterotopic pregnancy (47.1%) and adnexal torsion (39.2%) were common in the first trimester, whereas appendicitis peaked in the second (80%) and third trimesters (66.7%). The increasing use of assisted reproductive technology (ART) has led to a rise in gynecological patients requiring surgery in the first trimester, resulting in more laparoscopic surgeries during this period. Interestingly, an increase in laparoscopic surgery was also observed in general surgery during the second and third trimesters. Perioperative tocolysis was more frequent (51.1% vs. 3.8%, p < 0.001) and of longer duration (4.6 ± 8.8 vs. 0.1 ± 0.6 days, p = 0.001) after general surgical procedures., Conclusion: Laparoscopic surgery during pregnancy offers several advantages such as shorter operative time and hospital stay. Since 2011, laparoscopic surgery for the entire gestational period has been on the rise., (© 2024 Japan Society of Obstetrics and Gynecology.)
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- 2025
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22. Emodin disrupts the KITENIN oncogenic complex by binding ErbB4 and suppresses colorectal cancer progression in dual blockade with KSRP-binding compound.
- Author
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Varlı M, Ji M, Kim E, Kim SJ, Choi B, Ha HH, Kim KK, Paik MJ, and Kim H
- Subjects
- Humans, Animals, Cell Line, Tumor, Mice, Mice, Nude, Molecular Docking Simulation, Mice, Inbred BALB C, Emodin pharmacology, Receptor, ErbB-4 metabolism, Receptor, ErbB-4 antagonists & inhibitors, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Colorectal Neoplasms metabolism
- Abstract
Background: The KITENIN/ErbB4 complex has been reported to participate in metastasis, which is the principal reason of death in most colorectal cancer patients., Purpose: New therapeutics need to be developed to suppress the malignant effects of the KITENIN/ErbB4 complex, which is related to drug resistance. The present study aimed to evaluate changes in cancer cell invasion capacity, transcriptional regulators, and cellular bioenergetics after targeting the KITENIN/ErbB4 complex with emodin. Moreover, we aimed to reveal the mechanistic effects of emodin and observe the dual blockade effects of ErbB4-targeted therapy with KH-type splicing regulatory protein (KSRP) and search for new alternative blockade pathways., Methods: Using in vitro, in vivo, molecular-docking, and metabolomics studies, we evaluated the anticancer effect of emodin alone or in combination with DKCC14S., Results: Emodin treatment decreased KITENIN and ErbB4 protein levels. The dysfunctional KITENIN/ErbB4 complex suppressed KITENIN-mediated cell invasion and downregulated AP-1 activity, aerobic glycolysis, and the levels of transcriptional regulators associated with cell metabolism. We conclude that emodin targets the KITENIN/ErbB4 complex and offering a novel mechanism by which it disrupts KITENIN-mediated signaling. Furthermore, we were demonstrated that the dual blocking effect of emodin and DKC-C14S on the KITENIN complex showed synergistic effects in suppressing colorectal cancer progression under in cell-based and animal assay., Conclusion: The results suggest that co-treatment with ErbB4 and KSRP-binding compounds could constitute a potential strategy for controlling colorectal cancer progression by disrupting the KITENIN complex., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)
- Published
- 2025
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23. Polyphenol extract from Tagetes erecta L. flowers stimulates osteogenesis via β-catenin activation.
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Sanjaya SS, Park J, Choi YH, Park HS, Sadanaga T, Jung MJ, and Kim GY
- Subjects
- Animals, Mice, Osteoporosis drug therapy, Glycogen Synthase Kinase 3 beta metabolism, Cell Differentiation drug effects, Core Binding Factor Alpha 1 Subunit metabolism, Alkaline Phosphatase metabolism, Cell Line, Zebrafish, Osteogenesis drug effects, beta Catenin metabolism, Plant Extracts pharmacology, Flowers chemistry, Polyphenols pharmacology, Molecular Docking Simulation, Tagetes chemistry, Osteoblasts drug effects
- Abstract
Background: Osteoporosis, a prevalent bone disorder, results in reduced bone mineral density and mass. With minimal side effects, medicinal plant-based natural remedies are increasingly explored for osteoporosis. However, the osteogenic potential of Tagetes erecta L. flower, traditionally used for cardiovascular and renal diseases, has not yet been studied., Objective: This study investigates the osteogenic effects of the polyphenol-enriched extract from T. erecta L. flowers (TE) and its main components on osteoblast differentiation, with an emphasis on anti-osteoporotic activity., Methods: The osteogenic activity of TE was assessed in MC3T3-E1 preosteoblast cells, analyzing osteogenic alkaline phosphatase (ALP) activity via a colorimetric assay and mineralization through Alizarin Red S staining over 14 d. Expression levels of osteogenic markers-transcription factor osterix (SP7), runt-related transcription factor 2 (RUNX2), and ALP-were quantified through quantitative reverse transcription-polymerase chain reaction and western blotting. In vivo effects were evaluated using zebrafish larvae for bone formation and anti-osteoporotic properties. Vertebral development was visualized by staining mineralized structures with calcein or Alizarin Red S. Prednisolone (PDS) was administered to zebrafish larvae to model osteoporosis. Furthermore, molecular docking simulations were conducted to assess the binding affinity of TE components to the ATP-binding pocket of glycogen synthase kinase-3β (GSK-3β), and their inhibitory potential on GSK-3β kinase activity was quantified by in vitro kinase assays. Cellular thermal shift assay (CETSA) was performed to monitor direct bindings of TE and its main components to GSK3-3β., Results: TE promoted vertebral and cranial bone formation in zebrafish larvae, elevating key osteogenic genes, such as sp7, runx2a, runx2b, and alpl. Among TE components, kaempferol and patuletin significantly enhanced vertebral formation, while isorhamnetin showed moderate effects. Patulitrin and quercetagetin did not increased vertebral formation. In MC3T3-E1 cells, TE increased ALP activity, mineralization, and the expression of SP7, RUNX2, and ALP. It also induced GSK-3β phosphorylation at serine 9 and promoted β-catenin nuclear translocation. Inhibition of β-catenin signaling reversed TE-induced osteogenic effects. Molecular docking suggested strong GSK-3β binding by TE components, with patuletin showing notable inhibition GSK-3β activity (half-maximal inhibitory concentration = 379.3 ng/mL) and enhancing vertebral formation. CETSA confirmed that TE and its main components, kaempferol and patuletin, degrades GSK-3β. Additionally, TE alleviated PDS-induced osteoporosis in both cellular and zebrafish models., Conclusion: By targeting GSK-3β and activating β-catenin-mediated pathways, TE shows promise as a novel anti-osteoporotic agent. This study highlights the potential of TE for therapeutic use in bone health, warranting further clinical trials to confirm its applicability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)
- Published
- 2025
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24. In silico modeling of electric field modulation by transcranial direct current stimulation in stroke patients with skull burr holes: Implications for safe clinical application.
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Yoon MJ, Kim H, Yoo YJ, Im S, Kim TW, Dhaher YY, Kim D, and Lim SH
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Stroke Rehabilitation methods, Electrodes, Magnetic Resonance Imaging, Transcranial Direct Current Stimulation methods, Stroke physiopathology, Computer Simulation, Skull surgery
- Abstract
Background: Transcranial direct current stimulation (tDCS) has emerged as a promising tool for stroke rehabilitation, supported by evidence demonstrating its beneficial effects on post-stroke recovery. However, patients with skull defects, such as burr holes, have been excluded from tDCS due to limited knowledge regarding the effect of skull defects on the electric field., Objective: We investigated the effect of burr holes on the electric field induced by tDCS and identified the electrode location that modulates the electric field., Methods: We generated mesh models of the heads of five patients with burr holes and five age-matched control patients who had never undergone brain surgery, based on magnetic resonance imaging. Then we conducted tDCS simulations, with the cathode fixed in one position and the anode in various positions. Regression analysis was employed to investigate the relationship between the electric field at the burr hole and the distance from the burr hole to the anode., Results: In patients with burr holes, the electric field intensity increased as the anode approached the burr hole, reaching a maximum electric field when the anode covered it, with this pattern remaining consistent across all patient models. Assuming the holes were filled with cerebrospinal fluid, the maximum electric field was 1.20 ± 0.20 V/m (mean ± standard deviation, SD). When the anode was positioned more than 60 mm away from the burr hole, the electric field at the burr hole remained low and constant, with an average value of 0.29 ± 0.04V/m (mean ± SD). In contrast, for all patients without burr holes, the electric field intensity stayed constant regardless of the anode's position, with a maximum amplitude of 0.36 ± 0.04 V/m (mean ± SD). Furthermore, when the burr hole was assumed to be filled with scar tissue, the mean peak electric field was 0.93 ± 0.16 V/m, indicating that the electric field strength varies depending on the conductivity of the tissue filling the burr hole., Conclusion: Based on the simulations, the minimum recommended distance from the burr hole to the anode is 60 mm to prevent unintended stimulation of the brain cortex during tDCS. These findings will contribute to the development of safe and effective tDCS treatments for patients with burr holes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships that may be considered potential competing interests: Donghyeon Kim has equity in Neurophet, Inc. Hyungtaek Kim is employed by Neurophet, Inc. No other author has any potential conflict of interest relevant to this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2025
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25. Comparative analysis of the oncologic outcomes and risk factors for open conversion in laparoscopic surgery for non-metastatic colorectal cancer: A retrospective multicenter study.
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Kang JH, Kim EM, Kim MJ, Oh BY, Yoon SN, Kang BM, and Kim JW
- Subjects
- Humans, Male, Female, Retrospective Studies, Middle Aged, Aged, Risk Factors, Postoperative Complications epidemiology, Colectomy methods, Neoplasm Staging, Adult, Colorectal Neoplasms surgery, Colorectal Neoplasms pathology, Laparoscopy, Conversion to Open Surgery statistics & numerical data, Length of Stay, Operative Time
- Abstract
Purpose: Laparoscopic colon surgery is now commonly used for colorectal cancer (CRC) resection. The objective of this study was to compare the oncologic outcomes between open conversion and laparoscopic surgery, and to identify risk factors for open conversion., Methods: We retrospectively reviewed the medical records of patients who underwent curative resection for stage 0-III CRC at five Hallym University-affiliated hospitals between January 2011 and June 2021. The patients were divided into the conversion and laparoscopic groups according to whether laparoscopic surgery was completed., Results: Out of 2231 patients, laparoscopic surgery was completed in 2131 patients and 100 (4.5 %) converted to open surgery. The operation time (P = 0.028) and postoperative hospital stay (P = 0.036) were longer in the conversion group than in the laparoscopic group. Overall (P = 0.022) and severe (Clavien-Dindo classification grade ≥3) (P = 0.048) complications were more frequent in the conversion group than in the laparoscopic group. The 5-year recurrence-free survival (RFS) rate was worse in the conversion group than in the laparoscopic group (P = 0.002). In the multivariable analysis, open conversion was not a prognostic factor for RFS (P = 0.082). Abdominal surgery history (P = 0.021), obstruction (P < 0.001), and T4 stage (P < 0.001) were independently associated with open conversion., Conclusion: The conversion group had worse perioperative and oncologic outcomes. History of abdominal surgery, obstruction, and T4 stage were associated with open conversion. However, conversion itself was not associated with RFS., Competing Interests: Declarations of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)
- Published
- 2025
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26. Lactobacillus paragasseri SBT2055 attenuates obesity via the adipose tissue-muscle-gut axis in obese mice.
- Author
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Kim MJ, Shin SK, Han JW, Kim JE, Lee MJ, Bae HR, and Kwon EY
- Subjects
- Animals, Mice, Male, Lactobacillus, Adipose Tissue metabolism, Sarcopenia prevention & control, Feces microbiology, Muscle, Skeletal drug effects, Adipose Tissue, White drug effects, Adipose Tissue, White metabolism, Disease Models, Animal, Lipid Metabolism drug effects, Gastrointestinal Microbiome drug effects, Obesity microbiology, Mice, Inbred C57BL, Diet, High-Fat adverse effects, Probiotics administration & dosage, Probiotics pharmacology, Mice, Obese
- Abstract
The anti-obesity effects of Lactobacillus paragasseri (L. paragasseri) have been reported, but the exact mechanisms have not been elucidated. There are also no reports on the impact of L. paragasseri on the gut microbiota environment. Recently, the incidence of sarcopenia due to obesity has increased regardless of age, exacerbating metabolic disorders caused by obesity. Therefore, we investigate the beneficial effects of L. paragasseri SBT2055 (LG2055) on obesity along with obese sarcopenia and gut microbiome changes. C57BL/6 J mice were fed a high-fat diet (HFD) and LG2055 (1×10
8 or 1×1010 CFU/mice, low-dose LG2055 (LP) or high-dose LG2055 (HP), respectively was administered orally. LG2055 supplementation significantly reduced white adipose tissues compared to the HFD group and modified plasma lipid profiles to normal levels. The anti-obesity efficacy of LG2055 was due to increased lipid excretion into feces by reducing the mRNA levels of fatty acid binding protein 1 (Fabp1), fatty acid binding protein 2 (Fabp2), fatty acid transport protein 4 (Fatp4), cluster of differentiation 36 (Cd36), and apolipoprotein 48 (ApoB48) in the small intestine. The body fat reduction inhibits ectopic lipid accumulation in the muscles, leading to improvements in muscle mass, grip strength, hind leg thickness, muscle protein levels, and muscle fiber size in both LP and HP groups. LG2055 increased gut microbiota diversity and elevated the levels of Bacteroidota, resulting in a lower Firmicutes/Bacteroidota ratio compared to the HFD group. Changes in the Bacteroidota showed a negative correlation with body fat and plasma free fatty acid (FFA) while exhibiting a positive correlation with lean body mass, grip strength, and hind leg thickness. Our results demonstrated the anti-obesity effects of LG2055 through the white adipose tissue (WAT)-muscle-gut axis, suggesting its potential as an anti-obesity agent., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)- Published
- 2025
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27. Validation of the High-Performance Liquid Chromatography Method for Determining Quercitrin in Capsicum annuum L. Cultivar Dangjo.
- Author
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Fauziah AN, Kim MJ, So BR, Son JE, and Jung SK
- Abstract
Capsicum annuum L. cultivar Dangjo (DJ), developed as a novel crop, possesses potential health benefits, such as reducing blood glucose levels. DJ contains flavonoid glycosides, bioactive compounds that have been found in various plants and have promising pharmacological effects. A representative flavonol glycoside is quercitrin, a standard compound. Notwithstanding, its adoption by the food industry, it is necessary to standardize the quantification of quercitrin in DJ. Thus, an analytical method needs to be developed and validated to quantify quercitrin accurately. In this study, we established a high-performance liquid chromatography (HPLC) method for quantifying quercitrin in DJ extracts (DJEs); then, we validated the method, to ensure its accuracy and reliability. Our results demonstrated that the HPLC method effectively detecteds quercitrin in DJE samples, consistently reporting retention times and peak spectra similar to those in the standard solutions. The linearity assessment revealed a linear response within the concentration range of 2.5 to 15.0 μg/mL, which was supported by strong correlation coefficients (R
2 >0.9997). Accuracy assessment via recovery studies produced satisfactory results (89.02%-99.30%), with a relative standard deviation (RSD) within acceptable limits (0.50%-5.95%). Precision analysis confirmed the repeatability and reproducibility of the method, with RSD values within the Association of Official Agricultural Chemists (AOAC) standard criteria (≤8%). Overall, our study provides a validated HPLC method for quercitrin quantification in DJEs, facilitating its standardization and ensuring the accuracy of the analysis. This method is potentially valuable for quality control and further research on the health-promoting properties of DJ., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (© 2024 The Korean Society of Food Science and Nutrition.)- Published
- 2024
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28. Magnolia kobus DC. Regulates Vascular Smooth Muscle Cell Proliferation by Modulating O -GlcNAc and MOF Expression.
- Author
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Na HJ, Kim JM, Kim Y, Lee SH, and Sung MJ
- Abstract
Vascular smooth muscle cells (VSMCs) undergo metabolic pathway transitions, including aerobic glycolysis, fatty acid oxidation, and amino acid metabolism, which are important for their function. Metabolic dysfunction in VSMCs can lead to age-related vascular diseases. O -GlcNAcylation, a nutrient-dependent posttranslational modification linked specifically to glucose metabolism, plays an important role in this context. Magnolia kobus DC. (MK), derived from the flower buds of Magnolia biondii , is known for its anticancer, anti-allergy, and anti-inflammatory properties. However, the role of O -GlcNAcylation in VSMCs under aging and the association between MK and O -GlcNAc remain unclear. Therefore, the present study aimed to determine the effects of O -GlcNAc on VSMC proliferation, along with the expression of MOF (males absent on the first, KAT8) and its correlation with the efficacy of MK. The results showed that aging and O -GlcNAc induction increased the expression levels of O -GlcNAc, O -GlcNAc transferase (OGT), ataxia telangiectasia mutated (ATM) protein, and MOF in mouse vascular smooth muscle cells (MOVAS) and aorta tissue. Transfection with OGT siRNA reduced the expression of MOF and OGT, indicating that OGT regulates MOF and influences cell proliferation. MK treatment reduced the expression of OGT, ATM, and MOF, which was correlated with O -GlcNAc levels. These findings suggest that O -GlcNAcylation is important for VSMC homeostasis and may be a novel target for vascular diseases. Thus, MK exhibits potential as a new drug candidate for treating vascular diseases by modulating O -GlcNAcylation and MOF interactions., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (© 2024 The Korean Society of Food Science and Nutrition.)
- Published
- 2024
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29. Cesarean Delivery Upon Request in Pregnancies Following Vaginal Delivery: A Nationwide Study.
- Author
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Jung YM, Wi W, Cho KD, Hong SJ, Oh MJ, Cho GJ, and Park JS
- Subjects
- Humans, Female, Pregnancy, Adult, Retrospective Studies, Odds Ratio, Pregnancy Outcome, Cesarean Section, Trial of Labor, Delivery, Obstetric
- Abstract
Background: The increasing rate of cesarean delivery (CD) is a significant concern in many societies worldwide. Vaginal delivery (VD) is preferred over CD for subsequent pregnancies after successful VD, for women with no specific obstetrical indications, primarily because of concerns about potential complications arising from the surgical procedure. However, the factors that influence the decision of requesting a CD have not yet been thoroughly investigated. This study aimed to examine the underlying reasons that lead mothers to choose CDs in subsequent pregnancies following a VD., Methods: This retrospective study included women who underwent VD in their first pregnancy between 2011 and 2020 and had a second pregnancy and childbirth within the study period. The analysis focused on women eligible for a trial of labor (TOL) in their second pregnancy, excluding those with conditions necessitating a CD. The study defined two groups: the TOL in second pregnancy (TOLS) group, consisting of women with one previous VD who attempted a VD in their subsequent pregnancy; and the CD on maternal request in second pregnancy (CDRS) group, comprising women with one past VD who opted for a CD in their second pregnancy without medical indication. The TOLS and CDRS groups were compared regarding obstetric and neonatal outcomes., Results: During the study period, 372,749 women met the inclusion criteria: 368,311 women in TOLS group and 4,438 women in CDRS group. In the regression analysis for the CDRS, several factors were identified as increasing the risk of choosing CD, including age (adjusted odds ratio [aOR], 1.06; 95% confidence interval [CI], 1.05-1.07), interval between the first and second pregnancies (aOR, 1.32; 95% CI 1.29-1.35), a history of pre-existing hypertension (aOR, 1.76; 95% CI, 1.17-2.65), gestational diabetes mellitus (GDM) during the first pregnancy (aOR, 1.19; 95% CI, 1.05-1.36), hypertensive disease during pregnancy (HDP) (aOR, 1.33; 95% CI, 1.06-1.67), preterm labor during the first pregnancy (aOR, 1.57; 95% CI, 1.32-1.86), postpartum hemorrhage (aOR, 1.33; 95% CI, 1.21-1.47), traumatic event during delivery (aOR, 1.19; 95% CI, 1.12-1.28), surgical VD (aOR, 1.29; 95% CI, 1.19-1.40), and pregnancies with abortive outcomes between the first and second pregnancies (aOR, 1.18; 95% CI, 1.08-1.29). Additionally, women with pre-existing diabetes (aOR, 1.53; 95% CI, 1.24-1.89), pre-existing hypertension (aOR, 1.69; 95% CI, 1.26-2.26), GDM (aOR, 1.23; 95% CI, 1.11-1.37), or HDP (aOR, 2.57; 95% CI, 2.24-2.94) during the second pregnancy continued to exhibit an increased risk of opting for CD even after adjustment., Conclusion: CD after VD was more prevalent among women with certain demographic characteristics and obstetric histories. Investigating the factors influencing women to request CD can be helpful in making informed decisions about safe delivery methods and may also affect the CD rate., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)
- Published
- 2024
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30. Cognitive and neurodegenerative trajectories of subjective cognitive decline according to baseline biomarkers: Results of the CoSCo study.
- Author
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Hong YJ, Choi SH, Kim S, Jeong JH, Park KH, Wang MJ, Kang S, and Yang DW
- Abstract
Introduction: Alzheimer's disease (AD) is now diagnosed biologically. Since subjective cognitive decline (SCD) may indicate preclinical AD, assessing AD-biomarkers is crucial. We investigated cognitive and neurodegenerative trajectories in SCD over 24 months based on biomarker positivity, and evaluated the predictive value of plasma biomarkers., Methods: The CoSCo prospective cohort included older adults with SCD. Participants were categorized into high- and low-risk groups based on plasma biomarkers (amyloid beta [Aβ] 42/40, phosphorylated tau 181 [p-tau181], and glial fibrillary acidic protein [GFAP]), and magnetic resonance imaging (MRI) findings to compare outcomes., Results: High-risk SCDs (n = 23, 23%) revealed greater decline in general cognition, memory recall, frontal function, and hippocampal volumes compared to low-risk SCDs. Combined scores of plasma and MRIs yielded the best predictions compared with other biomarker categories., Discussion: SCD participants with high-risk experience faster cognitive and neurodegenerative declines. A combination of plasma biomarkers and MRIs could be used for screening and prognosis., Highlights: This is part of a multicenter prospective cohort study in Korea. We investigated cognitive and atrophic trajectories in SCD over 24 months. High risk SCDs revealed greater cognitive decline and hippocampal atrophy. Integration of plasma and MRIs yielded better predictions than other categories. Risk stratification using plasma and MRIs can be used for screening and prognosis., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
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- 2024
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31. Green Tea Attenuates the Particulate Matter (PM) 2.5 -Exposed Gut-Brain Axis Dysfunction through Regulation of Intestinal Microenvironment and Hormonal Changes.
- Author
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Kim JM, Lee HL, Go MJ, Kim HJ, Sung MJ, and Heo HJ
- Subjects
- Animals, Mice, Brain drug effects, Brain metabolism, Plant Extracts pharmacology, Male, Cytokines metabolism, Fatty Acids, Volatile metabolism, Hormones metabolism, Hormones blood, Intestines drug effects, Intestines microbiology, Antioxidants metabolism, Particulate Matter, Gastrointestinal Microbiome drug effects, Tea chemistry, Mice, Inbred BALB C, Brain-Gut Axis drug effects
- Abstract
Chronic exposure to particulate matter (PM)
2.5 causes brain damage through intestinal imbalance. This study was estimated to confirm the regulatory activity of green tea against chronic PM2.5 exposure-induced abnormal gut-brain axis (GBA) in BALB/c mice. The green tea, as an aqueous extract of matcha (EM), ameliorated the colon length, short chain fatty acid contents, antioxidant biomarkers, myeloperoxidase (MPO) activity, and serum inflammatory cytokines. EM regulated the gut microbiota related to tryptophan intake and hormone metabolism. EM showed regulatory effect of intestinal tight junction (TJ) protein, inflammatory response, and apoptotic biomarkers. In addition, EM improved PM2.5 -induced tryptophan-related hormonal metabolic dysfunction in intestinal tissue and serum. Through the ameliorating effect on GBA function, the consumption of EM presented the protective effect against inflammatory effect, apoptosis, synaptic damage, and hormonal activity in cerebral tissue, and suppressed abnormal change of brain lipid metabolites. In particular, EM intake showed relatively excellent improvement effects on indicators including Bacteroides , Ruminococcus , Murinobaculaceae , Allopreyotella , cyclooxygenase-2 (COX-2), acetylcholinesterase (AChE), 11,12-dihydroxyeicosatrienoic acid (DHET), and intestinal acetate from the PM group. These findings indicate that the dietary intake of EM might provide a regulatory effect against PM2.5 -exposed GBA dysfunction via the intestinal microbiota and hormonal changes.- Published
- 2024
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32. Structure-guided design of a peripherally restricted chemogenetic system.
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Kang HJ, Krumm BE, Tassou A, Geron M, DiBerto JF, Kapolka NJ, Gumpper RH, Sakamoto K, Dewran Kocak D, Olsen RHJ, Huang XP, Zhang S, Huang KL, Zaidi SA, Nguyen MT, Jo MJ, Katritch V, Fay JF, Scherrer G, and Roth BL
- Subjects
- Animals, Humans, Mice, Neurons metabolism, Designer Drugs pharmacology, Designer Drugs chemistry, Blood-Brain Barrier metabolism, Action Potentials drug effects, Male, HEK293 Cells, Pain metabolism, Rats, Mice, Inbred C57BL, Ganglia, Spinal metabolism, Cryoelectron Microscopy
- Abstract
Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools for remotely controlling cellular signaling, neural activity, behavior, and physiology. Using a structure-guided approach, we provide a peripherally restricted Gi-DREADD, hydroxycarboxylic acid receptor DREADD (HCAD), whose native receptor is minimally expressed in the brain, and a chemical actuator that does not cross the blood-brain barrier (BBB). This was accomplished by combined mutagenesis, analoging via an ultra-large make-on-demand library, structural determination of the designed DREADD receptor via cryoelectron microscopy (cryo-EM), and validation of HCAD function. Expression and activation of HCAD in dorsal root ganglion (DRG) neurons inhibit action potential (AP) firing and reduce both acute and tissue-injury-induced inflammatory pain. The HCAD chemogenetic system expands the possibilities for studying numerous peripheral systems with little adverse effects on the central nervous system (CNS). The structure-guided approach used to generate HCAD also has the potential to accelerate the development of emerging chemogenetic tools for basic and translational sciences., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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33. Lesson for the clinical nephrologist: thrombotic microangiopathy associated with metastatic prostate cancer.
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Tümay C, Sachs A, Stiefel I, and Kim MJ
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Competing Interests: Declarations. Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest. Ethical approval: This case report was conducted in compliance with ethical standards for research involving human subjects. All procedures conformed to the ethical standards of the institutional and/or national research committee and adhered to the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Human and animal rights: This case report does not contain any studies with human participants or animals performed by any of the authors. Informed consent: Written informed consent was obtained from the patient for publication of this case.
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- 2024
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34. Discovery of Isograndidentatin D, a Novel Phenolic Glycoside, and Anti- Helicobacter pylori Phenolics from Salix koreensis Twigs.
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Jang YS, Kang DM, Ko YJ, Ra MJ, Jung SM, Ahn MJ, Lee S, and Kim KH
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Salix koreensis Anderss (Salicaceae), commonly referred to as Korean willow, is native to East Asia, particularly Korea and China, and it has been used in traditional Korean folk medicine for its potent anti-inflammatory, analgesic, and antioxidant properties. In our ongoing research efforts to discover biologically new natural products, phytochemical analysis on an ethanolic extract of S. koreensis twigs yielded the isolation and identification of ten phenolic compounds ( 1 - 10 ), including a newly discovered phenolic glycoside ( 1 ) named isograndidentatin D, isolated via HPLC purification. The structure of compound 1 was determined through extensive 1D and 2D NMR spectral data analysis and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). Its absolute configuration was established using DP4+ probability analysis combined with gauge-including atomic orbital NMR chemical shift calculations and chemical reaction methods. The other known compounds were identified as isograndidentatin B ( 2 ), trichocarposide ( 3 ), glanduloidin C ( 4 ), tremuloidin ( 5 ), 3- O -acetylsalicin ( 6 ), 2- O -acetylsalicin ( 7 ), salicin ( 8 ), salireposide ( 9 ), and coumaric acid ( 10 ), confirmed by comparing their NMR spectra with previously reported data and further verified through liquid chromatography/mass spectrometry (LC/MS) analysis. The isolated compounds 1 - 10 were tested for their anti- Helicobacter pylori activities. Among these, compounds 4 and 5 demonstrated moderate anti- H. pylori activity at a concentration of 100 μM. Specifically, compound 5 showed an inhibitory activity of 35.9 ± 5.4%, making it slightly more potent than compound 4 , with 34.0 ± 1.0% inhibition. These results were comparable to that of quercetin, a known anti- H. pylori agent used as a positive control in this study, which showed 38.4 ± 2.3% inhibition. The remaining compounds exhibited very weak inhibitory effects. This study highlights the potential of S. koreensis twigs as a valuable natural source of bioactive compounds for therapeutic applications against H. pylori .
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- 2024
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35. Preventing Breast Cancer-Related Lymphedema: A Comprehensive Analysis of a 9-Year Single-Center Experience of Prophylactic Lymphovenous Bypass.
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Cho MJ, Senger JL, Park KU, Hansotia K, Chratian S, Kadle R, and Skoracki RJ
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Background: Prophylactic lymphovenous bypass (pLVB) is a microsurgical technique aimed to prevent breast cancer-related lymphedema (BCRL) after axillary lymph node dissection (ALND) by redirecting lymphatic flow from the ligated lymphatics into neighboring veins. This report describes the authors' 9-year institutional experience of pLVB in patients undergoing ALND to prevent BCRL., Methods: Patients who underwent ALND were reviewed. Demographic and oncologic data were analyzed. The primary outcomes included limb circumference and perometry. The secondary outcomes included patient-reported outcomes, incidence of cellulitis, and need for therapeutic lymphovenous bypass (LVB). Furthermore, the study identified risk factors for the development of BCRL within the ALND plus pLVB population., Results: Of the 370 patients, 25% underwent ALND plus pLVB. Demographic and oncologic features were similar between the two cohorts, and the average follow-up time was 23 months. The rate of BCRL was 8.7% in the ALND plus pLVB group and 20.1% in the no-pLVB group (p < 0.05), whereas the postoperative circumferential measurements were significantly improved among the ALND plus pLVB patients. In addition, the patients treated with ALND plus pLVB had a lower incidence of positive symptoms of lymphedema (pain, tightness, heaviness) and were less likely to require therapeutic LVB. The medical history of cardiac arrythmia was identified as a risk factor for the development of lymphedema in the ALND plus pLVB cohort., Conclusions: Prophylactic lymphovenous bypass contributes to a decreased incidence of lymphedema as well as improved patient symptoms and limb functionality. Furthermore, pLVB modulates disease severity for patients who experience BCRL. The authors advocate that pLVBs should be routinely offered to breast cancer patients undergoing ALND., Competing Interests: DISCLOSURE: The authors have no financial disclosures or conflict of interest., (© 2024. Society of Surgical Oncology.)
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- 2024
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36. Correction to: Phylosymbiosis in Seven Wild Fish Species Collected Off the Southern Coast of Korea: Skin Microbiome Most Strongly Reflects Evolutionary Pressures.
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Han GH, Yu J, Kang MJ, Park MJ, Noh CH, Kim YJ, and Kwon KK
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- 2024
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37. Long-Chain Polysaturated Fatty Acid in Atrial Fibrillation-Associated Stroke: Lipidomic-GWAS Study.
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Jung Y, Kim B, Kim CK, Won HH, Suhyun C, Oh KM, Shin MJ, Hwang GS, and Seo WK
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Background and Purpose This study aimed to explore the relationship between lipidomic domains, particularly free fatty acids (FFAs), and the presence of AF in patients with acute stroke, and to identify mechanisms of AF-associated stroke through genetic studies. Methods A total of 483 patients of stroke in patients without AF (n = 391) and with AF (n = 92) were selected from a prospectively collected stroke registry. Lipidomic profiling was conducted and the lipid components associated with AF were explored using fold-change analyses and clustering. Genotyping was conducted through trait comparison. Colocalization was also performed. Results Among the lipidomic domains, the free fatty acid (FFA) class was positively associated with AF. Long-chain fatty acids with 14-24 carbons and unsaturated FFAs distinguished AF. Clustering analysis based on FFAs revealed differences in AF proportion across groups. GWAS identified two loci associated with clustered groups of FFA metabolites: near MIR548F3 associated with FFA 20:1, FFA 20:2, FFA 22:5, and FFA 22:6; and near RPL37A associated with FFA 22:5 and FFA 22:6. These loci were associated with increased fibrinogen levels. In the GWAS for the FFA metabolite-quantitative trial locus analysis, loci near rs28456 and rs3770088, and FFA 20:4-QTLs were co-localized with the eQTLs of FADS2, a gene involved in the peroxisome proliferative-activated receptor gamma-related signaling pathway, in the whole blood, left ventricle, and atrial appendage tissue. Conclusion Elevated FFA levels, especially those of long-chain unsaturated FFAs, are strongly associated with AF-associated stroke. This relationship is regulated by the peroxisome proliferator-activated receptor gamma-related signaling pathway., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)
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- 2024
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38. More than carriers, orosomucoids are key metabolic modulators.
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Heo MJ, Cheon I, and Kim KH
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Orosomucoids (ORMs) have historically been considered as carriers involved in drug and lipid delivery. However, recent studies indicate ORM2 as a hepatokine involved in metabolic regulation. Here, we highlight the functions of ORM2 in controlling metabolic health and disease, focusing on its newly discovered regulatory mechanisms., Competing Interests: Declaration of interests All authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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39. USP21-EGFR signaling axis is functionally implicated in metastatic colorectal cancer.
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Shin JH, Kim MJ, Kim JY, Choi B, Kang Y, Kim SH, Lee HJ, Kwon D, Cho YB, Kim KK, Chun E, and Lee KY
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The emerging role of ubiquitin-specific peptidase 21 (USP21) in stabilizing Fra-1 (FOSL1) highlights its involvement in promoting colorectal cancer (CRC) metastasis. Additionally, a reciprocal link between EGFR signaling and Fra-1 activation has been identified, mediated through matrix metalloproteinases (MMPs). However, the functional implications of the USP21-EGFR signaling axis in metastatic CRC (mCRC) are not fully understood. To investigate the clinical correlation between USP21 and EGFR expression, RNA-Seq data from tumor tissues (n = 27) and matched normal tissues (n = 27) of 27 mCRC patients were analyzed. Functional studies were performed, including the use of CRISPR/Cas9 to generate USP21-knockout (USP21-KO) CRC cells, in vitro assays for cancer progression and tumor formation, in vivo xenograft assays in NSG mice. Additionally, the therapeutic effect of the USP21 inhibitor, BAY-805, was evaluated. We found that elevated levels of USP21 and EGFR expression in mCRC patients were associated with poorer survival outcomes. Mechanistically, USP21 was found to enhance EGFR stability by deubiquitinating EGFR, leading to reduced EGFR degradation. USP21-KO colon cancer cells exhibited significantly reduced proliferation, migration, colony formation, and 3D tumor spheroid formation in response to EGF. Furthermore, the tumorigenic activity in vivo was markedly diminished in NSG mice xenografted with USP21-KO colon cancer cells. Importantly, BAY-805 demonstrated a notable inhibitory effect on the formation of 3D tumor spheroids in colorectal cancer cells stimulated with EGF. These findings suggest that USP21 could be a valuable therapeutic target and predictive biomarker for managing mCRC driven by EGF., Competing Interests: Competing interests: The authors declare no competing interests. Ethics declarations: Tumor and matched normal tissues from 27 patients with primary CRC were obtained in accordance with the ethical principles stated in the Declaration of Helsinki. This study was approved by the institutional review board of Samsung Medical Center (IRB# 2010-04-004). We obtained written informed consent from each patient prior to surgery for using their pathological specimens for research use. All animal experimental procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of the Bioanalysis Center Animal Facility (IACUC #: 23-10-01), GenNBio Inc., (© 2024. The Author(s).)
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- 2024
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40. Chronic Kidney Disease and Infection Risk: A Lower Incidence of Peritonsillar Abscesses in Specific CKD Subgroups in a 16-Year Korean Nationwide Cohort Study.
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Kwon MJ, Kang HS, Kim JH, Kim JH, Bang WJ, Yoo DM, Lee NE, Han KM, Kim NY, Choi HG, Kim MJ, and Kim ES
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Peritonsillar abscesses and deep neck infection are potentially serious infections among patients with chronic kidney disease (CKD), posing risks for severe complications and drawing significant public health concern. This nationwide, population-based longitudinal study (2002-2019) assessed the extended relationship between chronic kidney disease (CKD) and the likelihood of peritonsillar abscess and deep neck infection in a Korean cohort. Using a 1:4 propensity score overlap-weighted matching, we included 16,879 individuals with CKD and 67,516 comparable controls, accounting for demographic variables and comorbidities to ensure balanced group comparisons. Hazard ratios (HRs) and 95% confidence intervals (CIs) for deep neck infection and peritonsillar abscesses in relation to CKD history were calculated with a propensity score overlap-weighted Cox proportional hazards model. Our results revealed no significant increase in the overall incidence of deep neck infections or peritonsillar abscesses in CKD patients compared to controls. Interestingly, CKD patients demonstrated a 50% reduced likelihood of developing peritonsillar abscesses (HR 0.50; 95% CI = 0.30-0.83; p = 0.007), particularly among subgroups aged 70 years or older, females, non-smokers, rural residents, overweight individuals, and those with lower comorbidity burdens (e.g., absence of hypertension, hyperlipidemia, or hyperglycemia). In summary, the results suggest that lifestyle modifications and the effective management of comorbidities could reduce the risk of peritonsillar abscess in certain CKD subgroups. Our findings may help to alleviate public health concerns regarding peritonsillar abscesses and deep neck infections as CKD-related comorbidities.
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- 2024
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41. Metabolomic analysis combined with machine learning algorithms enables the evaluation of postharvest pecan color stability.
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Kang MJ, Pegg RB, Kerr WL, Wells ML, Conner PJ, and Suh JH
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- Carya chemistry, Carya metabolism, Anthocyanins chemistry, Anthocyanins metabolism, Algorithms, Flavonoids chemistry, Flavonoids metabolism, Machine Learning, Metabolomics, Color
- Abstract
Nut kernel color is a crucial quality indicator affecting the consumers first impression of the product. While growing evidence suggests that plant phenolics and their derivatives are linked to nut kernel color, the compounds (biomarkers) responsible for kernel color stability during storage remain elusive. Here, pathway-based metabolomics with machine learning algorithms were employed to identify key metabolites of postharvest pecan color stability. Metabolites in phenylpropanoid, flavonoid, and anthocyanin biosynthetic pathways were analyzed in the testa of nine pecan cultivars using liquid chromatography-mass spectrometry. With color measurements, different machine learning models were compared to find relevant biomarkers of pecan color phenotypes. Results revealed potential marker compounds that included flavonoid precursors and anthocyanidins as well as anthocyanins (e.g., peonidin, delphinidin-3-O-glucoside). Our findings provide a foundation for future research in the area, and will help select genes/proteins for the breeding of pecans with stable and desirable kernel color., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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42. Age- and oxidative stress-induced centrosome amplification and renal stones in Drosophila Malpighian tubules.
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Na HJ, Sung MJ, and Park JS
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- Animals, Reactive Oxygen Species metabolism, Disease Models, Animal, Oxidative Stress, Malpighian Tubules metabolism, Centrosome metabolism, Kidney Calculi etiology, Kidney Calculi metabolism, Aging metabolism, Drosophila
- Abstract
Renal diseases, including cancer, are rapidly increasing worldwide, driven by rising temperatures and changing diets, especially among younger people. Renal stones, a major risk for chronic renal disease, are increasingly common due to various health issues. Research on the underlying mechanisms, drug discovery, and the effects of aging and stress is limited. We used Drosophila, due to its similarity to the human renal system and ease of use, to identify cancer hallmarks and renal stone formation related to aging and oxidative stress. Our results indicate that centrosome amplification and stone formation increase with age and oxidative stress, and high sucrose feeding also heightens stone formation in the renal system. Our results show a close relationship between these diseases and aging, reactive oxygen species (ROS) stress, and chronic diseases. We suggest that the Drosophila renal model could be a powerful tool to study the relationship between age and age-related diseases and to discovering new agents for nephropathy., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists.)
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- 2024
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43. Urinary GADD45G Protein Excretion Is Associated with IgA Nephropathy Progression.
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Lee MJ, Yim H, Park JE, Park I, Kim H, and Shin GT
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Background : Growth arrest and DNA damage 45G (GADD45G) is a family of proteins involved in DNA damage response and cell growth arrest. In this study, we show evidence that urinary GADD45G protein is associated with the progression of IgA nephropathy. Methods : Patients diagnosed with IgA nephropathy without reversible acute kidney injury at study initiation and with at least one subsequent serum creatinine (SCr) measurement were included. A 50% or greater increase in SCr level was used as an endpoint for the deterioration of renal function. Enzyme-linked immunosorbent assay (ELISA) was performed using a Human GADD45G ELISA kit. Renal biopsy tissues were stained with a monoclonal mouse anti-GADD45G antibody. Results : Forty-five patients whose renal biopsy revealed IgA nephropathy were enrolled. Urinary GADD45G and urinary protein concentrations were 1.26 [0.69-2.20] μg/g creatinine and 0.65 [0.24-1.60] g/g creatinine, respectively. Urinary GADD45G showed significant positive correlations with SCr-slopes and urinary protein. The SCr-slope of the highest tertile group of urinary GADD45G (above 1.95 μg/g creatinine) was significantly higher than that of the lowest tertile group (below 0.90 μg/g). Univariate Cox regression analysis showed that urinary GADD45G was significantly associated with deterioration of renal function. A Kaplan-Meier test showed a significant difference in event-free survival for deterioration of renal function between the highest urinary GADD45G tertile group and other tertile groups. The area under the receiver operating characteristics (ROC) curve indicated urinary GADD45G had a good performance in predicting renal outcome (cut-off point 1.67 μg/g, positive predictive value 36.8%, negative predictive value 100%). Immunohistochemistry showed that GADD45G was expressed across all pathologic grades of IgA nephropathy and mainly detected in the cytoplasm of renal tubules, whereas no staining was noted in normal tissues. Conclusions : Urinary GADD45G excretion was significantly associated with kidney disease progression in patients with IgA nephropathy.
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- 2024
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44. Application of Pathomic Features for Differentiating Dysplastic Cells in Patients with Myelodysplastic Syndrome.
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Hong Y, Jeong S, Park MJ, Song W, and Lee N
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Myelodysplastic syndromes (MDSs) are a group of hematologic neoplasms accompanied by dysplasia of bone marrow (BM) hematopoietic cells with cytopenia. Recently, digitalized pathology and pathomics using computerized feature analysis have been actively researched for classifying and predicting prognosis in various tumors of hematopoietic tissues. This study analyzed the pathomic features of hematopoietic cells in BM aspiration smears of patients with MDS according to each hematopoietic cell lineage and dysplasia. We included 24 patients with an MDS and 21 with normal BM. The 12,360 hematopoietic cells utilized were to be classified into seven types: normal erythrocytes, normal granulocytes, normal megakaryocytes, dysplastic erythrocytes, dysplastic granulocytes, dysplastic megakaryocytes, and others. Four hundred seventy-six pathomic features quantifying cell intensity, shape, and texture were extracted from each segmented cell. After comparing the combination of feature selection and machine learning classifier methods using 5-fold cross-validation area under the receiver operating characteristic curve (AUROC), the quadratic discriminant analysis (QDA) with gradient boosting decision tree (AUROC = 0.63) and QDA with eXtreme gradient boosting (XGB) (AUROC = 0.64) showed a high AUROC combination. Through a feature selection process, 30 characteristics were further analyzed. Dysplastic erythrocytes and granulocytes showed lower median values on heatmap analysis compared to that of normal erythrocytes and granulocytes. The data suggest that pathomic features could be applied to cell differentiation in hematologic malignancies. It could be used as a new biomarker with an auxiliary role for more accurate diagnosis. Further studies including prediction survival and prognosis with larger cohort of patients are needed.
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- 2024
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45. Phylosymbiosis in Seven Wild Fish Species Collected Off the Southern Coast of Korea: Skin Microbiome Most Strongly Reflects Evolutionary Pressures.
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Han GH, Yu J, Kang MJ, Park MJ, Noh CH, Kim YJ, and Kwon KK
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- Animals, Republic of Korea, Gills microbiology, Biological Evolution, Species Specificity, Microbiota, Skin microbiology, Phylogeny, RNA, Ribosomal, 16S genetics, Fishes microbiology, Symbiosis, Bacteria classification, Bacteria genetics, Bacteria isolation & purification
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Phylosymbiosis is defined as the relationship in which the microbiome recapitulates the phylogeny of the host and has been demonstrated in a variety of terrestrial organisms, although it has been understudied in fish, the most phylogenetically diverse vertebrate. Given that the species-specificity of fish microbiomes was detected in multiple body parts and differed by body parts, we assumed that the phylogenetic reflection of the microbiome would differ across body parts. Thus, we analyze the difference of phylosymbiotic relationships in the microbial communities found in three body parts (skin, gills, and intestine) of seven wild fish species from four families (Labridae, Sebastidae, Sparidae, and Rajidae) via 16S rRNA gene amplicon sequencing. Fishes were purchased at Docheon port market in Tongyeong City, Korea and were transported to nearby research institutes for aliveness. Mantel tests using dissimilarity values of microbiomes and hosts' divergence times showed that the differences in microbial communities in all three body parts were related to the hosts' divergence time. This pattern was the most pronounced in the skin. Furthermore, fishes from the same family showed similar bacterial compositions on their skins and gills, with clear differences depending on the family, with the exception of Labridae. These results suggest that the skin microbiome is particularly vulnerable to evolutionary pressures. We hypothesized that the evolution of the fish immune system and the difference in feeding habits induced the stronger phylosymbiotic signal in the skin. Collectively, this dataset will be useful for understanding the fish microbiome and give insights into phylosymbiosis of aquatic animals across body parts., Competing Interests: Declarations. Ethics approval: All the experimental procedures were performed in accordance with the Institutional Animal Care and Use Committee (IACUC) guidelines for the care and use of animals. Han completed the course, ‘Usage and Managements of laboratory animals’ hosted by Bioethics Information Center (BIC). Yu, Kang, and Noh completed the course, ‘Usage and Managements of laboratory animals’ hosted by Korea Association For Laboratory Animals (KAFLA). Consent to Publish: All the authors consented to this paper’s publication. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)
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- 2024
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46. Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility.
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Kim D, Cho YH, Kang MJ, Lee SJ, Lee S, Yun BH, Chi H, An J, Lee K, Han J, Chi S, Song MY, Cha SH, and Lee EJ
- Abstract
Background: Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function., Methods: SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test., Results: The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight., Conclusion: These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts.
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- 2024
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47. Effects of Blue Light on Fruiting Body Production and Ergothioneine Content During Sawdust Cultivation of Shiitake ( Lentinula edodes ).
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Kim MJ, Jeong Y, Park MJ, Jang Y, and Ka KH
- Abstract
The cultivation period of shiitake ( Lentinula edodes ) is approximately 120-150 d, which is longer than that of other edible mushrooms. The development of fruiting bodies in shiitake is affected by light exposure. In this study, we investigated the effects of blue light on the production and ergothioneine contents of shiitake mushrooms. Fruiting body production (yield) on the medium irradiated with blue light increased in both cultivars (L808, 555 ± 60 g/3 kg medium; Sanbackhyang, 1090 ± 106 g/3 kg medium). Additionally, blue light increased the ergothioneine contents and antioxidative activities, and the ergothioneine content of L808 (about 2.8 mg/g) was higher than that of Sanbackhyang (about 1.2 mg/g). These results suggest that blue light is effective in shortening the cultivation period and increasing ergothioneine contents during shiitake cultivation., Competing Interests: There are no relevant financial or non-financial competing interests to report., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Korean Society of Mycology.)
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- 2024
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48. Anti-necroptotic effects of human Wharton's jelly-derived mesenchymal stem cells in skeletal muscle cell death model via secretion of GRO-α.
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Park SE, Kwon SJ, Kim SJ, Jeong JB, Kim MJ, Choi SJ, Oh SY, Ryu GH, Jeon HB, and Chang JW
- Subjects
- Humans, Animals, Mice, Female, Muscular Dystrophy, Duchenne therapy, Muscular Dystrophy, Duchenne metabolism, Muscular Dystrophy, Duchenne pathology, Disease Models, Animal, Pregnancy, Placenta metabolism, Placenta cytology, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells cytology, Wharton Jelly cytology, Necroptosis drug effects, Muscle, Skeletal metabolism
- Abstract
Human mesenchymal stem cells (hMSCs) have therapeutic applications and potential for use in regenerative medicine. However, the use of hMSCs in research and clinical medicine is limited by a lack of information pertaining to their donor-specific functional attributes. In this study, we compared the characteristics of same-donor derived placenta (PL) and Wharton's jelly (WJ)-derived hMSCs, we also compared their mechanism of action in a skeletal muscle disease in vitro model. The same-donor-derived hWJ- and hPL-MSCs exhibited typical hMSC characteristics. However, GRO-α was differentially expressed in hWJ- and hPL-MSCs. hWJ-MSCs, which secreted a high amount of GRO-α, displayed a higher ability to inhibit necroptosis in skeletal muscle cells than hPL-MSCs. This demonstrates the anti-necroptotic therapeutic effect of GRO-α in the skeletal muscle cell death model. Furthermore, GRO-α also exhibited the anti-necroptotic effect in a Duchenne muscular dystrophy (DMD) mouse model. Considering their potential to inhibit necroptosis in skeletal muscle cells, hWJ-MSCs and the derived GRO-α are novel treatment options for skeletal muscle diseases such as DMD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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49. Effects of high-fat diet on folic acid-induced kidney injury in mice.
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Kim D, Son M, Ha S, Kim J, Kim MJ, Yoo J, Kim BM, Chung HY, Lee H, Kim D, Kim S, and Chung KW
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- Animals, Mice, Male, Mice, Inbred C57BL, Kidney metabolism, Kidney pathology, Kidney drug effects, Fibrosis, Pyroptosis drug effects, Kidney Diseases metabolism, Kidney Diseases pathology, Kidney Diseases etiology, Kidney Diseases chemically induced, Lipid Metabolism drug effects, Signal Transduction drug effects, Folic Acid administration & dosage, Folic Acid pharmacology, Diet, High-Fat adverse effects, Obesity metabolism, Inflammasomes metabolism
- Abstract
Obesity is recognized as a significant contributor to the onset of kidney disease. However, the key processes involved in the development of kidney disease in obese individuals are not well understood. Here, we investigated the effects of high-fat diet (HFD)-induced obesity on folic acid (FA)-induced kidney injury in mice. Mice were fed an HFD for 12 weeks to induce obesity, followed by an additional intraperitoneal injection of FA. The results showed that mice fed HFD developed higher levels of kidney damage than those in the chow group. In contrast, mice exposed to both HFD and FA showed less fibrosis and inflammatory responses compared to the FA only treated group. Furthermore, the HFD with FA group exhibited elevated lipid accumulation in the kidney and reduced expression of mitochondrial proteins compared to the FA-treated group. Under in vitro experimental conditions, we found that lipid accumulation induced by oleic acid treatment reduced inflammatory and fibrotic responses in both renal tubules and fibroblasts. Finally, RNA sequencing analysis revealed that the inflammasome and pyroptosis signaling pathways were significantly increased in the HFD group with FA injection. In summary, these findings suggest that obesity increases renal injury due to a lack of appropriate inflammatory, fibrotic, and metabolic responses and the activation of the inflammasome and pyroptosis signaling pathways., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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50. Calorie restriction exacerbates folic acid-induced kidney fibrosis by altering mitochondria metabolism.
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Kim MJ, Hwang T, Ha S, Kim H, Kim J, Kim D, Yoo JA, Kim BM, Chung HY, Kim D, Lee J, Lee H, Kim S, and Chung KW
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- Animals, Male, Mice, Oxidative Phosphorylation drug effects, Cell Line, Acute Kidney Injury metabolism, Acute Kidney Injury chemically induced, Folic Acid pharmacology, Folic Acid administration & dosage, Caloric Restriction, Mitochondria metabolism, Mitochondria drug effects, Fibrosis, Kidney metabolism, Kidney drug effects, Kidney pathology, Mice, Inbred C57BL
- Abstract
Calorie restriction (CR) is known to confer health benefits, including longevity and disease prevention. Although CR is promising in preventing chronic kidney disease (CKD), its potential impact on the progression of kidney fibrosis from acute kidney injury (AKI) to CKD remains unclear. Here, we present evidence that CR exacerbates renal damage in a mouse model of folic acid (FA)-induced renal fibrosis by altering mitochondrial metabolism and inflammation. Mice subjected to CR (60% of ad libitum) for three days were subjected to high dose of FA (250 mg/kg) injection and maintained under CR for an additional week before being sacrificed. Biochemical analyses showed that CR mice exhibited increased kidney injury and fibrosis. RNA sequencing analysis demonstrated decreased electron transport and oxidative phosphorylation (OXPHOS) in CR kidneys with injury, heightened inflammatory, and fibrotic responses. CR significantly decreased OXPHOS gene and protein levels and reduced β-oxidation-associated proteins in the kidney. To determine whether defects in mitochondrial metabolism is associated with inflammation in the kidney, further in vitro experiments were performed. NRK52E kidney epithelial cells were treated with antimycin A to induce mitochondrial damage. Antimycin A treatment significantly increased chemokine expression via a STING-dependent pathway. Serum restriction in NRK49F kidney fibroblasts was observed to enhance the fibrotic response induced by TGFβ under in vitro conditions. In summary, our results indicate that CR exacerbates fibrosis and inflammatory responses in the kidney by altering mitochondrial metabolism, highlighting the importance of adequate energy supply for an effective response to AKI and fibrosis development., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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