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1.
J Food Sci ; 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39366779

ABSTRACT

The objective of this study was to optimize the microbial and ingredient composition of kombucha for enhanced production of gluconic acid (GA). Fourteen strains of Komagataeibacter spp. and one yeast strain of Dekkera sp. were isolated from kombucha. Among them, Komagataeibacter swingsii SS1 (SS1) and Komagataeibacter saccharivorans SS11 (SS11) were selected for their high GA production. A rapid reduction of pH, high GA content relative to acetic acid, and high cellulose production were observed in the tea infusion fermented by the microbial consortium (SS1 + SS11 + Dekkera bruxellensis Y24). From the correlation between the materials composition and quality indicators of kombucha, the decrease in pH was the most critical quality indicator of kombucha and the most closely related to GA content. Maximal GA production (11.7 mg/mL) was obtained under the conditions of 1% (w/v) tea extract, 8.5% (w/v) glucose, and 1.5% (v/v) ethanol through the optimization of materials composition by response surface methodology. The GA content of kombucha was enhanced threefold in comparison to general kombucha by fermentation with Komagataeibacter spp. and optimization of the composition of the ingredients. Overall, this study showed that a specific microbial consortium and materials composition could be established by correlation analysis among the ingredients, which results in increased GA levels in kombucha. These findings offer valuable foundational data for both commercial production and quality control of kombucha.

2.
Bioengineering (Basel) ; 11(9)2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39329605

ABSTRACT

Whole-spine radiography can be accomplished through two methods: (1) segmented imaging employing X-ray tube angulation and detectors, or (2) the Euronext Paris Advanced Orthopedic Solutions (EOS) 2D Imaging system that can capture the entire spine in a single image using X-ray tubes and detectors oriented at a 90-degree angle. This study aimed to establish optimal EOS examination parameters based on patient morphotype and scan speed to reduce patient radiation exposure, repeat examinations, heat stress on equipment, and X-ray tube cooling time. X-ray exposure conditions involved adjustments of scan speed ranging from two to four steps, contingent upon the patient's morphotype ('S', small body; 'M', medium body; and 'L', large body. Patient dose measurements were conducted 20 times for each set of conditions. When transitioning from an 'S' to an 'M' morphotype at a constant scan speed, the entrance skin dose (ESD) exhibited an increase of approximately 41.25 ± 4.57%. A similar change from an 'M' to an 'L' morphotype resulted in an ESD increase of roughly 59.56 ± 24.00%. A transition from an 'S' to an 'L' morphotype at the same scan speed manifested an ESD elevation of approximately 124.21 ± 26.96%. This study underscores significant variations in radiation dose, ranging from 40% to 50%, when altering morphotype while maintaining a consistent scan speed.

3.
Article in English | MEDLINE | ID: mdl-39312775

ABSTRACT

With the continued increase in the number of pieces of diagnostic medical radiography equipment being used, radiation shielding in radiology departments is becoming increasingly important. Lead is the most commonly used material for radiation protection; however, there are numerous disadvantages associated with the use of lead, including environmental hazards and harm to the human body. Alternative shielding materials that can be used as replacements include barium sulfate, tungsten, or bismuth. Among alternative materials, barium sulfate appears to be the most cost-effective and easiest to process. In the present study, before constructing shielding barriers, a barrier thickness program for lead-free barrier materials based on National Council on Radiation Protection and Measurements (NCRP) Report No. 147 was used to determine the appropriate barrier thickness. The required thickness for lead-free boards for each type of diagnostic radiography room was calculated based on a tertiary general hospital in the Republic of Korea.

4.
Environ Pollut ; 362: 124921, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39265764

ABSTRACT

Zinc oxide nanoparticles (ZnO-NPs) are nanomaterials mainly produced and used worldwide. They translocate to circulatory systems from various exposure routes. While blood and endothelial cells are persistently exposed to circulating ZnO-NPs, the potential risks posed by ZnO-NPs to the cardiovascular system are largely unknown. Our study identified the potential risk of thrombosis and disturbance of the blood-brain barrier (BBB) by coagulant activity on red blood cells (RBCs) caused by ZnO-NPs. ZnO-NPs promoted the externalization of phosphatidylserine and the generation of microvesicles through an imbalance of intracellular mechanisms regulating procoagulant activity in human RBCs. The coagulation cascade leading to thrombin generation was promoted in ZnO-NPs-treated human RBCs. Combined with human RBCs, ZnO-NPs caused coagulant activity on isolated rat RBCs and rat venous thrombosis models. We identified the erythrophagocytosis of RBCs into brain endothelial cells via increased PS exposure induced by ZnO-NPs. Excessive erythrophagocytosis contributes to disrupting the BBB function of endothelial cells. ZnO-NPs increased the procoagulant activity of RBCs, causing venous thrombosis. Excessive erythrophagocytosis through ZnO-NPs-treated RBCs resulted in the dysfunction of BBB. Our study will help elucidate the potential risk ZnO-NPs exert on the cardiovascular system.

5.
Aging Ment Health ; : 1-9, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39192708

ABSTRACT

OBJECTIVES: This study examined how resilience and coping strategies were associated with depressive symptoms among Korean American older adults during COVID-19. The prevalent depressive symptoms and low use of mental health services in this population have raised significant concerns among healthcare professionals. Therefore, this study aims to understand the relationships between resilience and coping types on depressive symptoms and provide valuable insights into addressing these issues within this ethnic group. METHOD: A cross-sectional survey was conducted with 132 Korean American older adults. Hierarchical linear regression analyses were performed to assess the effect of sociodemographic factors (age, gender, marital status, years of living in the U.S., self-rated health, financial security), resilience, and coping strategies (problem-focused coping, emotion-focused coping, avoidant coping) on depressive symptoms. Next, the interactions between resilience and three coping strategies for depressive symptoms were tested. RESULTS: The findings show that depressive symptoms were associated with financial security and avoidant coping. Also, resilience interacted with avoidant coping and emotion-focused coping. Among the participants with low resilience, depressive symptoms increased rapidly when avoidant and emotion-focused coping strategies increased, respectively. CONCLUSION: This study emphasizes the importance of culturally tailored interventions to promote resilience and decrease avoidant and emotion-focused coping among Korean American older adults.

6.
Stem Cell Res Ther ; 15(1): 245, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39113095

ABSTRACT

BACKGROUND: The establishment of stable porcine embryonic stem cells (pESCs) can contribute to basic and biomedical research, including comparative developmental biology, as well as assessing the safety of stem cell-based therapies. Despite these advantages, most pESCs obtained from in vitro blastocysts require complex media and feeder layers, making routine use, genetic modification, and differentiation into specific cell types difficult. We aimed to establish pESCs with a single cell-passage ability, high proliferative potency, and stable in long-term culture from in vitro-derived blastocysts using a simplified serum-free medium. METHODS: We evaluated the establishment efficiency of pESCs from in vitro blastocysts using various basal media (DMEM/F10 (1:1), DMEM/F12, and a-MEM) and factors (FGF2, IWR-1, CHIR99021, and WH-4-023). The pluripotency and self-renewal capacity of the established pESCs were analyzed under feeder or feeder-free conditions. Ultimately, we developed a simplified culture medium (FIW) composed of FGF2, IWR-1, and WH-4-023 under serum-free conditions. RESULTS: The pESC-FIW lines were capable of single-cell passaging with short cell doubling times and expressed the pluripotency markers POU5F1, SOX2, and NANOG, as well as cell surface markers SSEA1, SSEA4, and TRA-1-60. pESC-FIW showed a stable proliferation rate and normal karyotype, even after 50 passages. Transcriptome analysis revealed that pESC-FIW were similar to reported pESC maintained in complex media and showed gastrulating epiblast cell characteristics. pESC-FIW were maintained for multiple passages under feeder-free conditions on fibronectin-coated plates using mTeSR™, a commercial medium used for feeder-free culture, exhibiting characteristics similar to those observed under feeder conditions. CONCLUSIONS: These results indicated that inhibition of WNT and SRC was sufficient to establish pESCs capable of single-cell passaging and feeder-free expansion under serum-free conditions. The easy maintenance of pESCs facilitates their application in gene editing technology for agriculture and biomedicine, as well as lineage commitment studies.


Subject(s)
Embryonic Stem Cells , Animals , Culture Media, Serum-Free/pharmacology , Swine , Embryonic Stem Cells/metabolism , Embryonic Stem Cells/cytology , Cell Differentiation , Feeder Cells/cytology , Feeder Cells/metabolism , Cell Culture Techniques/methods , Cell Proliferation , Blastocyst/cytology , Blastocyst/metabolism , Cells, Cultured
7.
Sci Rep ; 14(1): 12226, 2024 05 28.
Article in English | MEDLINE | ID: mdl-38806600

ABSTRACT

The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.


Subject(s)
Chryseobacterium , Phenylacetates , Vagina , Female , Animals , Phenylacetates/metabolism , Phenylacetates/pharmacology , Vagina/microbiology , Mice , Humans , Chryseobacterium/metabolism , Candida albicans/metabolism , Candida albicans/drug effects , Symbiosis , Hydrogen-Ion Concentration , Gardnerella vaginalis/metabolism , Gardnerella vaginalis/drug effects , Disease Models, Animal , Vaginitis/microbiology , Vaginitis/metabolism , Vaginitis/drug therapy
8.
Biol Res ; 57(1): 35, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38812008

ABSTRACT

BACKGROUND: Genetically modified pigs are considered ideal models for studying human diseases and potential sources for xenotransplantation research. However, the somatic cell nuclear transfer (SCNT) technique utilized to generate these cloned pig models has low efficiency, and fetal development is limited due to placental abnormalities. RESULTS: In this study, we unprecedentedly established putative porcine trophoblast stem cells (TSCs) using SCNT and in vitro-fertilized (IVF) blastocysts through the activation of Wing-less/Integrated (Wnt) and epidermal growth factor (EGF) pathways, inhibition of transforming growth factor-ß (TGFß) and Rho-associated protein kinase (ROCK) pathways, and supplementation with ascorbic acid. We also compared the transcripts of putative TSCs originating from SCNT and IVF embryos and their differentiated lineages. A total of 19 porcine TSCs exhibiting typical characteristics were established from SCNT and IVF blastocysts (TSCsNT and TSCsIVF). Compared with the TSCsIVF, TSCsNT showed distinct expression patterns suggesting unique TSCsNT characteristics, including decreased mRNA expression of genes related to apposition, steroid hormone biosynthesis, angiopoiesis, and RNA stability. CONCLUSION: This study provides valuable information and a powerful model for studying the abnormal development and dysfunction of trophoblasts and placentas in cloned pigs.


Subject(s)
Blastocyst , Nuclear Transfer Techniques , Trophoblasts , Animals , Trophoblasts/metabolism , Swine , Cell Differentiation , Female , Stem Cells , Fertilization in Vitro/methods
9.
Biotechnol J ; 19(3): e2300552, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38528347

ABSTRACT

Production of therapeutic monoclonal antibody (mAb) in transgenic plants has several advantages such as large-scale production and the absence of pathogenic animal contaminants. However, mAb with high mannose (HM) type glycans has shown a faster clearance compared to antibodies produced in animal cells. The neonatal Fc receptor (FcRn) regulates the persistence of immunoglobulin G (IgG) by the FcRn-mediated recycling pathway, which salvages IgG from lysosomal degradation within cells. In this study, Fc-engineering of antirabies virus therapeutic mAb SO57 with the endoplasmic reticulum (ER)-retention peptide signal (Lys-Asp-Glu-Leu; KDEL) (mAbpK SO57) in plant cell was conducted to enhance its binding activity to human neonatal Fc receptor (hFcRn), consequently improve its serum half-life. Enzyme-linked immunosorbent assay (ELISA) and Surface plasmon resonance assay showed altered binding affinity of the Fc region of three different mAbpK SO57 variants [M252Y/S254T/T256E (MST), M428L/N434S (MN), H433K/N434F (HN)] to hFcRn compared to wild type (WT) of mAbpK SO57. Molecular modeling data visualized the structural alterations in these mAbpK SO57. All of the mAbpK SO57 variants had HM type glycan structures similar to the WT mAbpK SO57. In addition, the neutralizing activity of the three variants against the rabies virus CVS-11 was effective as the WT mAbpK SO57. These results indicate that the binding affinity of mAbpK SO57 variants to hFcRn can be modified without alteration of N-glycan structure and neutralization activity. Taken together, this study suggests that Fc-engineering of antirabies virus mAb can be applied to enhance the efficacy of therapeutic mAbs in plant expression systems.


Subject(s)
Histocompatibility Antigens Class I , Immunoglobulin G , Receptors, Fc , Humans , Antibodies, Monoclonal/metabolism , Histocompatibility Antigens Class I/genetics , Immunoglobulin G/biosynthesis , Immunoglobulin G/genetics , Polysaccharides , Receptors, Fc/genetics , Protein Engineering/methods , Plants/genetics , Plants/metabolism
10.
Sci Total Environ ; 921: 171059, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38378062

ABSTRACT

Emission uncertainty in North Korea can act as an obstacle when developing air pollution management plans in the country and neighboring countries when the transboundary transport of air pollutants is considered. This study introduces a novel approach for adjusting and reallocating North Korean CO emissions, aiming to complement the limited observational and emissions data on the country's air pollutants. We utilized ground observations from demilitarized zone (DMZ) and vertical column density (VCD) data from a TROPOspheric Monitoring Instrument (TROPOMI), which were combined with the Community Multi-Scale Air Quality (CMAQ) chemistry transport model simulations. The Clean Air Support System (CAPSS) and Satellite Integrated Joint Monitoring of Air Quality (SIJAQ) emissions inventories served as the basis for our initial simulations. A two-step procedure was proposed to adjust both the emission intensity and the spatial distribution of emissions. First, air quality simulations were conducted to explore model sensitivity to changes in North Korean CO emissions with respect to ground concentrations. DMZ observations then constrained these simulations to estimate corresponding emission intensity. Second, the spatial structure of North Korean CO emission sources was reconstructed with the help of TROPOMI CO VCD distributions. Our two-step hybrid method outperformed individual emissions adjustment and spatial reallocation based solely on surface or satellite observations. Validation using ground observations from the Chinese Dandong site near the China-North Korea border revealed significantly improved model simulations when applying the updated CO emissions. The adjusted CO emissions were 10.9 times higher than those derived from the bottom-up emissions used in this study, highlighting the lack of information on North Korean pollutants and emission sources. This approach offers an efficient and practical solution for identifying potential missing emission sources when there is limited on-site information about air quality on emissions.

11.
Cancers (Basel) ; 16(3)2024 Feb 03.
Article in English | MEDLINE | ID: mdl-38339410

ABSTRACT

BACKGROUND: The extra-capsular spread (ECS) of lymph node metastasis (LNM) is a hallmark of aggressive primary tumor phenotype in head and neck cancer (HNC); however, the factors influencing ECS are poorly understood. PATIENTS AND METHODS: This was a retrospective study, including 190 cases of oral tongue cancer (OTC), 148 cases of oropharyngeal cancer (OPC) (118 HPV-positive and 30 HPV-negative), and 100 cases of hypopharyngeal cancer (HPC). Tumor dimension, tumor biological variables (lymphovascular/perineural invasion and histologic grade), and LNM variables (LNM number and size) were analyzed according to the presence of ECS using multivariable logistic regression and receiver operating characteristic (ROC) curve analyses. RESULTS: LNM variables were significant factors for ECS in all subsites of HNC (p < 0.05), except HPV-positive OPC. In OTC, tumor dimensional variables were significantly related to ECS (p < 0.01). Meanwhile, in OPC and HPC, neither the primary tumor dimension nor the T status were significant factors for ECS occurrence. The predictability of ECS by ROC curve using multiple variables was 0.819 [95% confidence interval: 0.759-0.878] in OTC, 0.687 [0.559-0.815] in HPV-positive OPC, 0.823 [0.642-1.000] in HPV-negative OPC, and 0.907 [0.841-0.973] in HPC. CONCLUSION: LNM variables were correlated with ECS occurrence for most HNC subsites, and site-dependent primary tumor characteristics might contribute differentially to the ECS development of LNM in HNC.

12.
Biosensors (Basel) ; 14(1)2024 Jan 21.
Article in English | MEDLINE | ID: mdl-38275308

ABSTRACT

The development of therapeutic interventions for diseases necessitates a crucial step known as drug screening, wherein potential substances with medicinal properties are rigorously evaluated. This process has undergone a transformative evolution, driven by the imperative need for more efficient, rapid, and high-throughput screening platforms. Among these, microfluidic systems have emerged as the epitome of efficiency, enabling the screening of drug candidates with unprecedented speed and minimal sample consumption. This review paper explores the cutting-edge landscape of microfluidic-based drug screening platforms, with a specific emphasis on two pioneering approaches: organ-on-a-chip and C. elegans-based chips. Organ-on-a-chip technology harnesses human-derived cells to recreate the physiological functions of human organs, offering an invaluable tool for assessing drug efficacy and toxicity. In parallel, C. elegans-based chips, boasting up to 60% genetic homology with humans and a remarkable affinity for microfluidic systems, have proven to be robust models for drug screening. Our comprehensive review endeavors to provide readers with a profound understanding of the fundamental principles, advantages, and challenges associated with these innovative drug screening platforms. We delve into the latest breakthroughs and practical applications in this burgeoning field, illuminating the pivotal role these platforms play in expediting drug discovery and development. Furthermore, we engage in a forward-looking discussion to delineate the future directions and untapped potential inherent in these transformative technologies. Through this review, we aim to contribute to the collective knowledge base in the realm of drug screening, providing valuable insights to researchers, clinicians, and stakeholders alike. We invite readers to embark on a journey into the realm of microfluidic-based drug screening platforms, fostering a deeper appreciation for their significance and promising avenues yet to be explored.


Subject(s)
High-Throughput Screening Assays , Microfluidics , Animals , Humans , Caenorhabditis elegans , Drug Evaluation, Preclinical , Microphysiological Systems , Lab-On-A-Chip Devices
13.
Chemosphere ; 349: 140794, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38008293

ABSTRACT

The contribution of ozonation to the formation of particulate nitrosodi-methylamine (NDMA) in the aqueous aerosol phase was investigated using measurement data from 2018 in Seoul, Republic of Korea and a box model. The correlation between the NDMA concentration and aerosol liquid water content and box model results showed that aqueous aerosol phase reactions, including nitrosation and ozonation, might contribute to the formation of NDMA. The concentration of NDMA and the ratio of O3/dimethylamine exhibited a negative correlation, suggesting that the contribution of ozonation to NDMA formation may not be significant. Furthermore, when the daily concentration of NDMA exceeded 10 ng/m3, the pH was 3.96 ± 0.48, indicating that the impact of ozonation on NDMA concentration might not be significant. To quantitatively investigate the contribution of ozonation, the ozonation mechanism that forms NDMA was included in the box model developed in our previous study. The model results showed that the ozonation contributed to the ambient concentration of NDMA (7.9 ± 3.8% (winter); 1.9 ± 3.0% (spring); 10.0 ± 0.77% (summer); 3.6 ± 7.3% (autumn)). It is estimated that the relatively higher O3/NOx ratio in summer (1.63 ± 0.69; 0.64 ± 0.52 (winter); 1.14 ± 0.92 (spring); 0.52 ± 0.54 (autumn)) could enhance ozonation and that relatively lower pH in summer (2.2 ± 0.4; 5.3 ± 1.2 (winter); 3.9 ± 1.2 (spring); 3.9 ± 0.7 (autumn)) could hinder nitrosation compared to that in other seasons.


Subject(s)
Ozone , Water Pollutants, Chemical , Water Purification , Dimethylnitrosamine , Hydrogen-Ion Concentration , Water Pollutants, Chemical/analysis , Methylamines , Water , Atmosphere , Aerosols , Water Purification/methods
14.
Int J Mol Sci ; 24(23)2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38069329

ABSTRACT

Neuromuscular diseases (NMDs) are a genetically or clinically heterogeneous group of diseases that involve injury or dysfunction of neuromuscular tissue components, including peripheral motor neurons, skeletal muscles, and neuromuscular junctions. To study NMDs and develop potential therapies, remarkable progress has been made in generating in vitro neuromuscular models using engineering approaches to recapitulate the complex physical and biochemical microenvironments of 3D human neuromuscular tissues. In this review, we discuss recent studies focusing on the development of in vitro co-culture models of human motor neurons and skeletal muscles, with the pros and cons of each approach. Furthermore, we explain how neuromuscular in vitro models recapitulate certain aspects of specific NMDs, including amyotrophic lateral sclerosis and muscular dystrophy. Research on neuromuscular organoids (NMO) will continue to co-develop to better mimic tissues in vivo and will provide a better understanding of the development of the neuromuscular tissue, mechanisms of NMD action, and tools applicable to preclinical studies, including drug screening and toxicity tests.


Subject(s)
Neuromuscular Diseases , Humans , Muscle, Skeletal , Neuromuscular Junction , Motor Neurons , Organoids
15.
Front Vet Sci ; 10: 1285530, 2023.
Article in English | MEDLINE | ID: mdl-38033636

ABSTRACT

Stem cell factor (SCF), a cytokine growth factor, is expressed in various tissues of the male and female reproductive organs, including the testis, ovary, and endometrium. Its primary function involves cell survival, differentiation, and proliferation, achieved through its binding to the c-kit receptor. This study aimed to scrutinize the effects of SCF treatment during in vitro culture (IVC) on both the developmental potential and the efficiency of establishing embryonic stem cells (ESCs) from fertilized and cloned porcine embryos. The rates of cleavage and blastocyst formation exhibited no significant differences between fertilized and cloned embryos, even with the addition of SCF. However, it's worth noting that embryos cloned with Cloud eGFP as donor cells demonstrated notably increased rates of hatched blastocysts when treated with SCF, and this increase was statistically significant (p < 0.05). Furthermore, following the complete dissection of the blastocysts, although there was no significant difference in the SCF-treated group, the area of expansion was significantly reduced (p < 0.01) in the group treated with the antagonistic blocker (ACK2) compared to both the control and SCF-treated groups. These outcomes suggest that the SCF/c-kit signaling pathway might play a pivotal role in embryo implantation. As anticipated, the efficiency of deriving ESCs was significantly higher (p < 0.01) in the group subjected to SCF treatment (12.82 ± 1.02%) compared to the control group (5.41 ± 2.25%). In conclusion, this study highlights the crucial role of SCF in enhancing the quality of porcine embryos, a vital step in obtaining high-quality ESCs.

16.
J Korean Med Sci ; 38(41): e328, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37873628

ABSTRACT

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. METHODS: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009-2020 were enrolled. RESULTS: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. CONCLUSION: These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.


Subject(s)
Hemoglobinuria, Paroxysmal , Hypertension, Pulmonary , Renal Insufficiency , Thromboembolism , Humans , Middle Aged , Hemoglobinuria, Paroxysmal/drug therapy , Hemoglobinuria, Paroxysmal/complications , Hemoglobinuria, Paroxysmal/epidemiology , Hypertension, Pulmonary/complications , Renal Insufficiency/complications , Cost of Illness , Republic of Korea , Spasm/complications , Hemolysis
17.
Food Chem Toxicol ; 181: 114084, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37816477

ABSTRACT

Parabens are widely used as preservatives, added to products commonly used by humans, and to which individuals are exposed orally or dermally. Once absorbed into the body, parabens move into the bloodstream and travel through the systemic circulation. We investigated the potential impact of parabens on the enhanced generation of thrombin by red blood cells (RBCs), which are the principal cellular components of blood. We tested the effects of methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP), and p-hydroxybenzoic acid on freshly isolated human RBCs. BuP and simultaneous exposure to BuP and PrP significantly increased phosphatidylserine (PS) externalization to the outer membranes of RBCs. PS externalization by BuP was found to be mediated by increasing intracellular Ca2+ levels in RBCs. The morphological changes in BuP-treated RBCs were observed under an electron microscope. The BuP-exposed RBCs showed increased thrombin generation and adhesion to endothelial cells. Additionally, the externalization of PS exposure and thrombin generation in BuP-treated RBCs were more susceptible to high shear stress, which mimics blood turbulence under pathological conditions. Collectively, we observed that BuP induced morphological and functional changes in RBCs, especially under high shear stress, suggesting that BuP may contribute to the thrombotic risk via procoagulant activity in RBCs.


Subject(s)
Parabens , Phosphatidylserines , Humans , Parabens/toxicity , Calcium/pharmacology , Thrombin/pharmacology , Endothelial Cells , Erythrocytes
18.
J Xray Sci Technol ; 31(5): 1115-1124, 2023.
Article in English | MEDLINE | ID: mdl-37545249

ABSTRACT

BACKGROUND: Neonatal patients located in incubators are exposed to as many as 159 radiographs until discharge. To reduce the dose exposed to the patient, factors that may cause unnecessary exposure to the patient were judged. When conducting portable X-rays of neonatal patients located in an incubator, it is not easy to determine the exact field size because collimation light is exposed on the acrylic plate, an incubator canopy, and the resulting shadow is reflected on the patient's body. OBJECTIVE: This study aims to measure the organ dose exposed to the patient according to the field size when a portable radiograph is given to a neonatal patient in a neonatal intensive care unit (NICU) incubator. METHODS: To identify the absorbed organ dose depending on the radiation field size during portable X-ray examination of neonatal patient, a Monte Carlo N-Particle (MCNP) simulation, a SpeckCalc program, and a neonatal phantom from the ICRP 89 are applied for the calculation. According to the minimal field size (MinFS) standards of the European Commission (EC), the smaller field size is intended to measure tightly from the top of the lung apices to the bottom of the genitals; a larger field size is also calculated by adding 6 cm in width and length. RESULTS: Compared to the hospital C condition from the previous study, the larger and smaller field sizes are decreased by an average of 45% and 67%, respectively. Study results also show a 42% reduction in smaller field size compared to the larger field size. CONCLUSION: When taking chest and abdomen radiographic images of neonatal patients in incubators, appropriate field sizes are required to prevent inappropriate dose absorption for non-thoracic organs.


Subject(s)
Incubators , Infant, Newborn , Humans , X-Rays , Monte Carlo Method , Radiography , Phantoms, Imaging , Radiation Dosage
19.
Food Chem Toxicol ; 179: 113985, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37572985

ABSTRACT

Phthalates in contaminated foods and personal care products are one of the most frequently exposed chemicals with a public health concern. Phthalate exposure is related to cardiovascular diseases, including diabetic vascular complications and cerebrovascular diseases, yet the mechanism is still unclear. The blood-brain barrier (BBB) integrity disruption is strongly associated with cardiovascular and neurological disease exacerbation. We investigated BBB damage by di-(2-ethylhexyl) phthalate (DEHP) or its metabolite mono-(2-ethylhexyl) phthalate (MEHP) using brain endothelial cells and rat models. BBB damage by the subthreshold level of MEHP, but not a DEHP, significantly increased by the presence of methylglyoxal (MG), a reactive dicarbonyl compound whose levels increase in the blood in hyperglycemic conditions in diabetic patients. Significant potentiation in apoptosis and autophagy activation, mitochondria-derived reactive oxygen species (ROS) production, and mitochondrial metabolic disturbance were observed in brain ECs by co-exposure to MG and MEHP. N-acetyl cysteine (NAC) restored autophagy activation as well as tight junction protein impairment induced by co-exposure to MG and MEHP. Intraperitoneal administration of MG and MEHP significantly altered mitochondrial membrane potential and tight junction integrity in rat brain endothelium. This study may provide novel insights into enhancing phthalate toxicity in susceptible populations, such as diabetic patients.


Subject(s)
Diethylhexyl Phthalate , Rats , Animals , Diethylhexyl Phthalate/toxicity , Pyruvaldehyde , Blood-Brain Barrier/metabolism , Endothelial Cells/metabolism , Oxidative Stress , Energy Metabolism , Mitochondria/metabolism
20.
Nutrients ; 15(15)2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37571343

ABSTRACT

Hepatocellular carcinoma (HCC) has a poor prognosis and a low survival rate. Drugs without side effects are desperately needed since chemotherapy has a negative effect on the host cells. Previous research has firmly established that plant-based compounds have significant bioactivities without a negative impact on the host. Flavonoids, in particular, are a class of compounds with both anti-inflammatory and anti-cancer properties. Prunetrin (PUR) is a glycosyloxyisoflavone (Prunetin 4'-O-glucoside) derived from Prunus sp., and its other form, called prunetin, showed optimistic results in an anti-cancerous study. Hence, we aimed to discover the anti-cancer ability of prunetrin in liver cancer Hep3B cells. Our cytotoxicity results showed that PUR can decrease cell viability. The colony formation assay confirms this strongly and correlates with cell cytotoxicity results. Prunetrin, in a dose-dependent manner, arrested the cell cycle in the G2/M phase and decreased the expression of cyclin proteins such as Cyclin B1, CDK1/CDC2, and CDC25c. Prunetrin treatment also promoted the strong cleavage of two important apoptotic hallmark proteins called PARP and caspase-3. It also confirms that apoptosis occurs through the mitochondrial pathway through increased expression of cleaved caspase-9 and increased levels of the pro-apoptotic protein Bak. Bak was significantly increased with the declining expression of the anti-apoptotic protein Bcl-xL. Next, it inhibits the mTOR/AKT signaling pathways, proving that prunetrin includes apoptosis and decreases cell viability by suppressing these pathways. Further, it was also observed that the activation of p38-MAPK was dose-dependent. Taken together, they provide evidence that prunetrin has an anti-cancerous ability in Hep3B liver cancer cells by arresting the cell cycle via p38 and inhibiting mTOR/AKT.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Proto-Oncogene Proteins c-akt/metabolism , Carcinoma, Hepatocellular/metabolism , Flavonoids/pharmacology , Flavonoids/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Cell Cycle Checkpoints , Signal Transduction , Apoptosis , TOR Serine-Threonine Kinases/metabolism , Apoptosis Regulatory Proteins , Cell Line, Tumor , Cell Proliferation
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