21 results on '"Ryu, C."'
Search Results
2. Telomere Attrition Is Associated With Sarcoidosis
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Gandhi, S.S., primary, Lee, C., additional, Yu, S., additional, Saber, T., additional, Woo, S., additional, Mcgovern, J., additional, Fiorini, V., additional, Gulati, M., additional, Herzog, E., additional, and Ryu, C., additional
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- 2024
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3. MicroRNA Signatures Are Associated With Severe Skin and Pulmonary Involvement in Systemic Sclerosis
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Figueroa, A.A., primary, Zielonka, J., additional, Ramirez, M.A., additional, Ryu, C., additional, and Gomez, J.L., additional
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- 2024
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4. Role of Noradrenaline and Macrophage Dynamics in Pulmonary Fibrosis
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Ishikawa, G., primary, Peng, X., additional, Mcgovern, J., additional, Ghincea, A., additional, Saber, T., additional, Sun, H., additional, Sauler, M., additional, Ryu, C., additional, and Herzog, E., additional
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- 2024
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5. Innate Immune Effects of Α1-adrenoreceptor Antagonism in Sarcoidosis
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Saber, T., primary, Yu, S., additional, Lee, C.J., additional, Fiorini, V., additional, Mcgovern, J., additional, Woo, S., additional, Gulati, M., additional, Ryu, C., additional, and Herzog, E., additional
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- 2024
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6. Comparative Study of ESD and Surgical Resection for Gastric SETs Originated from MuscularisPropria
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Ryu, C. B., additional, Lee, M. S., additional, and Bae, J. Y., additional
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- 2024
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7. Long term outcomes of endoscopic submucosal dissection for undifferentiated early gastric cancer, beyond expanded criteria
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Ryu, C. B., additional, Lee, M. S., additional, and Bae, J. Y., additional
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- 2024
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8. Resistive Pulse Analysis of Chiral Amino Acids Utilizing Metal-Amino Acid Crystallization Differences
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Stringer, Blake, primary, Schmeltzer, Alexandra, additional, Ryu, C. Hyun, additional, Ren, Hang, additional, and Luo, Long, additional
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- 2024
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9. Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis.
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Unterman A, Zhao AY, Neumark N, Schupp JC, Ahangari F, Cosme C Jr, Sharma P, Flint J, Stein Y, Ryu C, Ishikawa G, Sumida TS, Gomez JL, Herazo-Maya JD, Dela Cruz CS, Herzog EL, and Kaminski N
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- Humans, Male, Female, Middle Aged, Aged, Disease Progression, Case-Control Studies, Flow Cytometry, Idiopathic Pulmonary Fibrosis immunology, Single-Cell Analysis methods, T-Lymphocytes, Regulatory immunology, Leukocytes, Mononuclear immunology
- Abstract
Rationale: Changes in peripheral blood cell populations have been observed, but not detailed, at single-cell resolution in idiopathic pulmonary fibrosis (IPF). Objectives: We sought to provide an atlas of the changes in the peripheral immune system in stable and progressive IPF. Methods: Peripheral blood mononuclear cells (PBMCs) from patients with IPF and control subjects were profiled using 10× chromium 5' single-cell RNA sequencing. Flow cytometry was used for validation. Protein concentrations of regulatory T cells (Tregs) and monocyte chemoattractants were measured in plasma and lung homogenates from patients with IPF and control subjects. Measurements and Main Results: Thirty-eight PBMC samples from 25 patients with IPF and 13 matched control subjects yielded 149,564 cells that segregated into 23 subpopulations. Classical monocytes were increased in patients with progressive and stable IPF compared with control subjects (32.1%, 25.2%, and 17.9%, respectively; P < 0.05). Total lymphocytes were decreased in patients with IPF versus control subjects and in progressive versus stable IPF (52.6% vs. 62.6%, P = 0.035). Tregs were increased in progressive versus stable IPF (1.8% vs. 1.1% of all PBMCs, P = 0.007), although not different than controls, and may be associated with decreased survival ( P = 0.009 in Kaplan-Meier analysis; and P = 0.069 after adjusting for age, sex, and baseline FVC). Flow cytometry analysis confirmed this finding in an independent cohort of patients with IPF. The fraction of Tregs out of all T cells was also increased in two cohorts of lung single-cell RNA sequencing. CCL22 and CCL18, ligands for CCR4 and CCR8 Treg chemotaxis receptors, were increased in IPF. Conclusions: The single-cell atlas of the peripheral immune system in IPF reveals an outcome-predictive increase in classical monocytes and Tregs, as well as evidence for a lung-blood immune recruitment axis involving CCL7 (for classical monocytes) and CCL18/CCL22 (for Tregs).
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- 2024
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10. Plasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts.
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Sand JMB, Jessen H, Leeming DJ, Yu S, Lee CJ, Hu B, Sun Y, Adams T, Pivarnik T, Liu A, Woo S, McGovern JR, Fiorini V, Saber T, Higuero-Sevilla JP, Gulati M, Kaminski N, Damsky W, Shaw AC, Mohanty S, Goobie G, Zhang Y, Herzog EL, and Ryu C
- Abstract
Introduction: The pathogenesis of sarcoidosis involves tissue remodelling mediated by the accumulation of abnormal extracellular matrix, which is partly the result of an imbalance in collagen synthesis, cross-linking and degradation. During this process, collagen fragments or neoepitopes, are released into the circulation. The significance of these circulating collagen neoepitopes in sarcoidosis remains unknown., Methods: We employed plasma samples from patients with sarcoidosis enrolled in A Case Control Etiologic Study of Sarcoidosis (ACCESS) and Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS), and healthy control patients recruited from the Yale community. Plasma concentrations of type III and VI collagen degradation (C3M and C6M) and formation (PRO-C3 and PRO-C6) were quantified via neoepitope-specific competitive ELISA, and statistical associations were sought with clinical phenotypes., Results: Relative to healthy controls, the plasma of both sarcoidosis cohorts was enriched for C3M and C6M, irrespective of corticosteroid use and disease duration. While circulating collagen neoepitopes were independent of Scadding stage, there was a significant association between multiorgan disease and PRO-C3, PRO-C6 and C3M in the ACCESS cohort; PRO-C3 and C6M displayed this property in GRADS. These findings were unrelated to plasma levels of interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10 and IL-13. Moreover, PRO-C3 was associated with dermatological disease in both cohorts., Discussion: In two well-characterised sarcoidosis cohorts, we discovered that the plasma is enriched for neoepitopes of collagen degradation (C3M and C6M). In multiorgan disease, there was an association with circulating neoepitopes of type III formation (PRO-C3), perhaps mediated by dermatological sarcoidosis. Further investigation in this arena has the potential to foster new insights into the pathogenic mechanisms of this complex disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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11. Comparison between upper and lower airway microbiome profiles in chronic rhinosinusitis patients.
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Hernaiz-Leonardo JC, Ryu C, Pascual A, Fan J, Caray M, Pezato R, Yang J, Sin D, and Thamboo A
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- Humans, Female, Middle Aged, Male, Chronic Disease, Adult, Aged, Bronchi microbiology, RNA, Ribosomal, 16S genetics, Bacteria isolation & purification, Bacteria genetics, Bacteria classification, Lung microbiology, Rhinosinusitis, Sinusitis microbiology, Rhinitis microbiology, Microbiota, Asthma microbiology, Paranasal Sinuses microbiology
- Abstract
Background: Dysregulation of the airway microbiota is thought to contribute to airway inflammation in both chronic rhinosinusitis (CRS) and asthma. However, the relationship between the upper and lower airway microbiome remains unclear., Methods: Sinus and lung brushes were collected from 29 CRS participants undergoing sinus surgery. DNA was extracted and submitted for 16s rRNA microbiome sequencing. Alpha and beta diversity metrics, taxonomic composition, and differences between individual taxa were compared for paired sinus and bronchial samples., Results: Twenty-three out of 29 participants had sufficient samples for analysis. The mean (standard deviation) age was 51.59 (14.57) years, and 10 (44%) patients were female. Twelve (52%) patients had comorbid asthma. Sinus brushes had significantly higher alpha diversity indexes (Shannon and Faith) compared to bronchial brushes (p < 0.001). Beta diversity metrics were significantly different between the sinus and bronchial samples. Principal coordinate analysis showed no clustering of paired nasal and bronchial samples. Sinus brushes had significantly more Lawsonella, Corynebacterium, and Staphylococcus compared to bronchia brushes, while the latter were enriched in Tropheryma and Sphingomonas, among others (false discovery rate [FDR]-adjusted p < 0.01). Finally, CRS patients with comorbid asthma had significantly higher Pseudomonas and Peptoniphilus in sinus brushes and lower Prevotella in bronchial brushes when compared to non-asthmatics (FDR-adjusted p < 0.01)., Conclusion: The sinus and bronchial bacterial microbiomes differ in important ways. Our study suggests that migration of bacteria from the sinus into the lower airways is unlikely in patients with CRS., (© 2024 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)
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- 2024
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12. A Phase I, Open-Label, Sequential, Single-Dose Clinical Trial to Evaluate the Pharmacokinetic, Pharmacodynamic, and Safety of IVL3001, a Finasteride-Based Novel Long-Acting Injection for Androgenetic Alopecia.
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Kim H, Ryu C, Lee M, Lee KR, and Kim J
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- Humans, Male, Adult, Dihydrotestosterone pharmacokinetics, Dihydrotestosterone administration & dosage, Dihydrotestosterone blood, Middle Aged, Delayed-Action Preparations, Testosterone pharmacokinetics, Testosterone blood, Injections, Subcutaneous, Young Adult, Microspheres, Finasteride pharmacokinetics, Finasteride administration & dosage, Finasteride adverse effects, Alopecia drug therapy, 5-alpha Reductase Inhibitors pharmacokinetics, 5-alpha Reductase Inhibitors administration & dosage, 5-alpha Reductase Inhibitors adverse effects, 5-alpha Reductase Inhibitors pharmacology
- Abstract
Introduction: Hair loss is driven by multiple factors, including genetics. Androgenetic alopecia (AGA) is a condition in which treatments necessitate prolonged compliance with prescribed medications. We have developed IVL3001, a long-acting injectable (LAI) formulation of finasteride encapsulated within poly lactic-co-glycolic acid microspheres, to enhance the efficacy of the finasteride and to achieve consistent positive outcomes in adults. An open-label, sequential, single-dose phase I clinical trial was designed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) of IVL3001., Methods: A total of 40 non-smoking, healthy adult males were divided into three cohorts where the IVL3001 group received a single subcutaneous injection of 12-36 mg IVL3001 and 1 mg finasteride (Propecia
® ) once daily for 28 days. The plasma concentrations of finasteride, dihydrotestosterone (DHT), and testosterone were measured using liquid chromatography-tandem mass spectrometry. The tolerability of the injections was assessed, and compartment models were developed to predict the effective dose and assess PK/PD profiles., Results: IVL3001 and finasteride 1 mg tablets were well tolerated. IVL3001 showed consistent plasma concentrations without bursts or fluctuations. Consistent with its mechanism of action, IVL3001 reduced DHT levels. Simulation data showed that the administration of 12-36 mg of IVL3001 every 4 weeks achieved plasma concentrations similar to finasteride, with comparable DHT reduction., Conclusion: The present study represents the first clinical trial to evaluate the safety, pharmacokinetic (PK), pharmacodynamic (PD), and tolerability of finasteride long-acting injectables (LAI) in adults. The rapid onset of action sustained effective drug concentration and the prolonged half-life of IVL3001 suggest that it offers multiple benefits over conventional oral formulations in terms of therapeutic response and compliance., Trial Registration: ClinicalTrials.gov identifier, NCT04945226., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)- Published
- 2024
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13. Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
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Zhao AY, Unterman A, Abu Hussein NS, Sharma P, Nekola F, Flint J, Yan X, Adams TS, Justet A, Sumida TS, Zhao J, Schupp JC, Raredon MSB, Ahangari F, Deluliis G, Zhang Y, Buendia-Roldan I, Adegunsoye A, Sperling AI, Prasse A, Ryu C, Herzog E, Selman M, Pardo A, and Kaminski N
- Abstract
Rationale : Fibrotic hypersensitivity pneumonitis is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives : To elucidate immune aberrations in fibrotic hypersensitivity pneumonitis in single-cell resolution. Methods : Single-cell 5' RNA sequencing was conducted on peripheral blood mononuclear cells and bronchoalveolar lavage cells obtained from 45 patients with fibrotic hypersensitivity pneumonitis, 63 idiopathic pulmonary fibrosis, 4 non-fibrotic hypersensitivity pneumonitis, and 36 healthy controls in the United States and Mexico. Analyses included differential gene expression (Seurat), transcription factor activity imputation (DoRothEA-VIPER), and trajectory analyses (Monocle3/Velocyto-scVelo-CellRank). Measurements and Main Results : Overall, 501,534 peripheral blood mononuclear cells from 110 patients and controls and 88,336 bronchoalveolar lavage cells from 19 patients were profiled. Compared to controls, fibrotic hypersensitivity pneumonitis has elevated classical monocytes (adjusted-p=2.5e-3) and are enriched in CCL3
hi /CCL4hi and S100Ahi classical monocytes (adjusted-p<2.2e-16). Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis. Compared to both controls and idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis patient cells are significantly enriched in GZMhi cytotoxic T cells. These cells exhibit transcription factor activities indicative of TGFβ and TNFα/NFκB pathways. These results are publicly available at https://ildimmunecellatlas.org. Conclusions : Single-cell transcriptomics of fibrotic hypersensitivity pneumonitis patients uncovered novel immune perturbations, including previously undescribed increases in GZMhi cytotoxic CD4+ and CD8+ T cells - reflecting this disease's unique inflammatory T-cell driven nature - as well as increased S100Ahi and CCL3hi /CCL4hi classical monocytes also observed in idiopathic pulmonary fibrosis. Both cell populations may guide the development of new biomarkers and therapeutic interventions.- Published
- 2024
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14. A Case of Bilateral Diffuse Uveal Melanocytic Proliferation Followed by Massive Unilateral Uveal Proliferation.
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Ryu C, Havens SJ, Chen J, DiMaio DJ, and Rishi P
- Abstract
Objective: To report a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) followed by massive unilateral uveal proliferation., Methods: Retrospective case report., Results: A 47-year-old female with history of metastatic ovarian carcinoma initially presented with bilateral vision loss and multifocal red patches on posterior poles consistent with BDUMP. Five years later, she presented with bilateral neovascular glaucoma and unilateral iris and ciliary body mass concerning for malignancy. Enucleation revealed diffuse uveal growth involving almost the entirety of the uveal tract., Conclusions: BDUMP can rarely be associated with uveal proliferation. Routine examinations are recommended to monitor for any changes concerning malignancy.
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- 2024
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15. Sodium Bicarbonate Decreases Alcohol Consumption in Mice.
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Lin J, Rivadeneira AP, Ye Y, Ryu C, Parvin S, Jang K, Garraway SM, and Choi I
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- Animals, Mice, Male, Female, Hydrogen-Ion Concentration, Ethanol, Sucrose pharmacology, Quinine pharmacology, Taste drug effects, Alcohol Drinking, Sodium Bicarbonate pharmacology, Mice, Inbred C57BL, Reward
- Abstract
We previously reported that mice with low neuronal pH drink more alcohol, demonstrating the importance of pH for alcohol reward and motivation. In this study, we tested whether systemic pH affects alcohol consumption and if so, whether it occurs by changing the alcohol reward. C57BL/6J mice were given NaHCO
3 to raise their blood pH, and the animals' alcohol consumption was measured in the drinking-in-the-dark and two-bottle free choice paradigms. Alcohol consumption was also assessed after suppressing the bitterness of NaHCO3 with sucrose. Alcohol reward was evaluated using a conditioned place preference. In addition, taste sensitivity was assessed by determining quinine and sucrose preference. The results revealed that a pH increase by NaHCO3 caused mice to decrease their alcohol consumption. The decrease in high alcohol contents (20%) was significant and observed at different ages, as well as in both males and females. Alcohol consumption was also decreased after suppressing NaHCO3 bitterness. Oral gavage of NaHCO3 did not alter quinine and sucrose preference. In the conditioned place preference, NaHCO3 -treated mice spent less time in the alcohol-injected chamber. Conclusively, the results show that raising systemic pH with NaHCO3 decreases alcohol consumption, as it decreases the alcohol reward value.- Published
- 2024
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16. Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts.
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Fiorini V, Hu B, Sun Y, Yu S, McGovern J, Gandhi S, Woo S, Turcotte-Foster SJ, Pivarnik T, Khan Z, Adams T, Herzog EL, Kaminski N, Gulati M, and Ryu C
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- Humans, Male, Female, Middle Aged, Adult, Toll-Like Receptor 9 genetics, Toll-Like Receptor 9 blood, Cohort Studies, DNA, Mitochondrial blood, DNA, Mitochondrial genetics, Fatigue blood, Fatigue etiology, Sarcoidosis blood, Sarcoidosis complications, Sarcoidosis genetics
- Abstract
Background: Patients with sarcoidosis who develop severe clinical phenotypes of pulmonary fibrosis or multiorgan disease experience debilitating symptoms, with fatigue being a common chief complaint. Studies that have investigated this patient-related outcome measure (PROM) have used the Fatigue Assessment Scale (FAS), a self-reported questionnaire that reflects mental and physical domains. Despite extensive work, its cause is unknown and treatment options remain limited. Previously, we showed that the plasma of patients with sarcoidosis with extrapulmonary disease endorsing fatigue was enriched for mitochondrial DNA (mtDNA), a ligand for the innate immune receptor toll-like receptor 9 (TLR9). Through our cross-disciplinary platform, we investigated a relationship between sarcoidosis-induced fatigue and circulating mtDNA., Research Question: Is there a psychobiologic mechanism that connects sarcoidosis-induced fatigue and mtDNA-mediated TLR9 activation?, Study Design and Methods: Using a local cohort of patients at Yale (discovery cohort) and the National Institutes of Health-sponsored Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis study (validation cohort), we scored the FAS and quantified in the plasma, mtDNA concentrations, TLR9 activation, and cytokine levels., Results: Although FAS scores were independent of corticosteroid use and Scadding stage, we observed a robust association between FAS scores, which included mental and physical domains, and multiorgan sarcoidosis. Subsequently, we identified a significant correlation between plasma mtDNA concentrations and all domains of fatigue. Additionally, we found that TLR9 activation is associated with all aspects of the FAS and partially mediates this PROM through mtDNA. Last, we found that TLR9-associated soluble mediators in the plasma are independent of all facets of fatigue., Interpretation: Through our cross-disciplinary translational platform, we identified a previously unrecognized psychobiologic connection between sarcoidosis-induced fatigue and circulating mtDNA concentrations. Mechanistic work that investigates the contribution of mtDNA-mediated innate immune activation in this PROM and clinical studies with prospective cohorts has the potential to catalyze novel therapeutic strategies for this patient population and those with similar conditions., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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17. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract.
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Mao T, Kim J, Peña-Hernández MA, Valle G, Moriyama M, Luyten S, Ott IM, Gomez-Calvo ML, Gehlhausen JR, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee CJ, Silva Monteiro V, Lucas C, Dong H, Yang Y, Gopinath S, Wilen CB, Palm N, Dela Cruz CS, and Iwasaki A
- Subjects
- Animals, Mice, Humans, COVID-19 immunology, COVID-19 prevention & control, COVID-19 virology, Respiratory Tract Infections immunology, Respiratory Tract Infections drug therapy, Respiratory Tract Infections virology, Respiratory Tract Infections prevention & control, Nasal Mucosa immunology, Nasal Mucosa virology, Nasal Mucosa drug effects, Disease Models, Animal, COVID-19 Drug Treatment, Mesocricetus, Female, Influenza A virus drug effects, Influenza A virus immunology, Neomycin pharmacology, Neomycin administration & dosage, Administration, Intranasal, Antiviral Agents pharmacology, Antiviral Agents administration & dosage, SARS-CoV-2 immunology, SARS-CoV-2 drug effects
- Abstract
Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections., Competing Interests: Competing interests statement:A.I. co-founded and consults for RIGImmune, Xanadu Bio and PanV, consults for Paratus Sciences, InvisiShield Technologies, and is a member of the Board of Directors of Roche Holding Ltd.
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- 2024
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18. Effects of Heat Stress on the Laying Performance, Egg Quality, and Physiological Response of Laying Hens.
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Kim HR, Ryu C, Lee SD, Cho JH, and Kang H
- Abstract
As high temperature and relative humidity (RH) are the main environmental factors causing heat stress, the temperature-humidity index (THI) serves as an indicator of heat stress in livestock animals. This study aimed to determine the effects of heat stress on the laying performance, physiological responses, egg quality, and blood profile of laying hens by subjecting them to environmental conditions with varying THI levels (68-85) for 28 days. The indicators of laying performance, such as feed intake (-30%) and egg production rate (-11%), significantly decreased in the hens exposed to severe heat stress (33 °C, 66% RH) compared to those exposed to thermoneutral conditions (21 °C, 68% RH). Moreover, severe heat stress reduced the egg yolk color, eggshell thickness and strength, and Haugh units of the eggs produced by the laying hens. Furthermore, a significant increase in serum K
+ and a decrease in Na+ levels were observed in the hens subjected to severe heat stress compared with those under thermoneutral conditions. Our results indicate that heat stress alters the physiological responses and metabolism of laying hens, resulting in a lower egg quality and production rate.- Published
- 2024
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19. Damage sensing through TLR9 Promotes Viral Clearance and Recovery During Influenza Infection.
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Kim J, Yuan Y, Agaronyan K, Zhao A, Wang VD, Gupta G, Essayas H, Kaminski A, McGovern J, Yu S, Woo S, Lee CJ, Saleh T, Hu B, Sun Y, Ishikawa G, Bain W, Evankovich J, Herzog EL, Cruz CSD, Ryu C, and Sharma L
- Abstract
Host response aimed at eliminating the infecting pathogen, as well as the pathogen itself, can cause tissue injury. Tissue injury leads to the release of a myriad of cellular components including mitochondrial DNA, which the host senses through pattern recognition receptors. How the sensing of tissue injury by the host shapes the anti-pathogen response remains poorly understood. In this study, we utilized mice that are deficient in toll-like receptor-9 (TLR9), which binds to unmethylated CpG DNA sequences such as those present in bacterial and mitochondrial DNA. To avoid direct pathogen sensing by TLR9, we utilized the influenza virus, which lacks ligands for TLR9, to determine how damage sensing by TLR9 contributes to anti-influenza immunity. Our data show that TLR9-mediated sensing of tissue damage promotes an inflammatory response during early infection, driven by the myeloid cells and associated cytokine responses. Along with the diminished inflammatory response, the absence of damage sensing through TLR9 led to impaired viral clearance manifested as a higher and prolonged influenza burden in the lung. The absence of TLR9 led to extensive infection of myeloid cells including monocytes and macrophages rendering them highly inflammatory, despite having a low initial inflammatory response. The persistent inflammation driven by infected myeloid cells led to persistent lung injury and impaired recovery in influenza-infected TLR9-/- mice. Further, we show elevated circulating TLR9 ligands in the plasma samples of patients with influenza, demonstrating its clinical relevance. Overall, over data show an essential role of damage sensing through TLR9 in promoting anti-influenza immunity.
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- 2024
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20. Superior Ophthalmic Vein Thrombosis Associated With Asymptomatic COVID-19 Infection.
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Menke BA, Ryu C, and Chundury RV
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- Female, Humans, Aged, Eye blood supply, Diplopia etiology, Venous Thrombosis etiology, Venous Thrombosis complications, COVID-19 complications, Exophthalmos etiology, Thrombosis, Varicose Veins complications
- Abstract
Superior ophthalmic vein thrombosis is a rare condition scarcely described in clinical literature with potentially severe consequences including permanent vision loss. This report details the case of a 70-year-old woman who presented with acute binocular horizontal diplopia, relative proptosis of the OD by 4 mm, and pain OD. On exam, visual acuity was 20/20 OD and 20/30 OS with full extraocular movements. CT revealed proptosis OD with a thrombosed superior ophthalmic varix. Evaluation for etiology of hypercoagulability was unremarkable, although the patient did have an asymptomatic COVID-19 infection 1 month prior. To the authors' knowledge, this is the first reported case of superior ophthalmic vein thrombosis secondary to an asymptomatic COVID-19 infection., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)
- Published
- 2024
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21. Evaluation of Food Effect on the Pharmacokinetics of Velufenacin, a New Muscarinic Receptor Antagonist, in Healthy Subjects.
- Author
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Khwarg J, Chung WK, Lee S, Yang E, Ryu C, Lee DY, Lee MJ, Jang IJ, Yu KS, and Lee S
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- Humans, Healthy Volunteers, Cross-Over Studies, Administration, Oral, Receptors, Muscarinic, Meals, Muscarinic Antagonists adverse effects
- Abstract
Velufenacin (DA-8010) is a new muscarinic receptor antagonist under development for the treatment of overactive bladder. This study aimed to evaluate the effect of food on the pharmacokinetics (PK) and safety of velufenacin in healthy subjects. A randomized, open-label, single-dose, 4-sequence, 4-treatment, 4-period crossover study was conducted. Subjects received a single oral dose of velufenacin 2.5 or 5 mg in a fasted or fed (high-fat meal) state in each period with a 7-day washout. PK parameters including maximum plasma concentration (C
max ) and area under the concentration-time curve from time 0 to the last measurable point were compared between the fed and fasted states. Twenty-seven subjects completed the study. The mean area under the concentration-time curve from time 0 to the last measurable point of the velufenacin 2.5 and 5 mg doses under the fed condition showed a 1.5- and 1.3-fold increase, respectively, compared to the fasted condition. The corresponding values for Cmax were a 2.3- and 2.0-fold increase, respectively. The time to reach Cmax was comparable regardless of the dose or food intake, showing median values of 4.5-5.0 hours. These results suggest a modest increase of velufenacin absorption by food intake. Velufenacin was generally safe and well tolerated at the 2.5 and 5 mg doses regardless of food., (© 2023, The American College of Clinical Pharmacology.)- Published
- 2024
- Full Text
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