Short-term Clinical Outcomes after Flanged Intrascleral Fixation of Intraocular Lenses Using Oblique Intrascleral Tunnels

Purpose@#To report the short-term clinical outcomes after intrascleral fixation of intraocular lenses (IOLs) using oblique intrascleral tunnels. @*Methods@#We retrospectively studied 17 patients (18 eyes) who underwent flanged intrascleral IOL fixation from October 2019 to October 2021. The patients were divided into those who underwent fixation using horizontal (group A) and oblique (group B) intrascleral tunnels. We compared the best-corrected visual acuities (BCVAs), cylindrical powers, refractive errors (the differences between the targeted spherical equivalents [SEs] and postoperative SEs) before and 3 months after surgery, and operating times. @*Results@#At 3 months vs. preoperatively, there were no significant differences in BCVA (-0.83 ± 0.43 vs. -0.48 ± 0.59), refractive error (-0.06 ± 0.97 diopter [D] vs. -0.05 ± 0.80 D), cylindrical power (-0.42 ± 3.81 D vs. -0.33 ± 1.20 D), or operating time (83.33 ± 28.05 minutes [min] vs. 66.33 ± 20.57 min) between groups A and B, respectively. @*Conclusions@#In terms of the short-term clinical outcomes after use of horizontal and oblique intrascleral tunnels, we found no significant differences in any parameters studied. However, use of an oblique intrascleral tunnel may shorten the operating time.

Exposure to Hazardous Substances and Their Health Effects Among Residents Living Near Three Industrial Waste Incinerators in Korea

Background@#This study aimed to evaluate exposure to various hazardous substances emitted by incineration facilities and their likely effect on the health for residents of Bugi-myeon, Cheongju, Korea, which has three incineration facilities. @*Methods@#Heavy metals, polycyclic aromatic hydrocarbons (PAHs), and dioxin concentrations in the air and soil of exposed and control areas were measured. Moreover, the exposure levels to harmful substances and its effects on health were investigated in 1,124 exposed and 232 control adults. @*Results@#PAHs and dioxin concentrations in the air in the exposed area were significantly higher than in the control area. Urinary cadmium and PAHs metabolite concentrations were significantly higher in the exposed group than in the control group. The exposure group also had a higher prevalence of depression and self-reported allergic symptoms than the control group. @*Conclusion@#The possibility of residents in Bugi-myeon being exposed to hazardous substances at incineration facilities cannot be ruled out. To prevent them from further exposure to hazardous substances, it is necessary to prohibit the expansion of additional incineration facilities in this area and to implement continuous monitoring projects for residents

Ghrelin Downregulates Lipopolysaccharide/ Leptin-Induced MUC5AC Expression in Human Nasal Epithelial Cells

Objectives@#. Obesity, which induces chronic low-grade systemic inflammation in the human body, is a known risk factor for various diseases. Recent studies have shown associations between various otorhinolaryngological diseases and obesity. In particular, inflammatory sinonasal diseases have been found to be strongly associated with obesity-related proinflammatory mediators. Many studies have been conducted to identify therapeutic agents for controlling obesity-related inflammatory airway diseases. Ghrelin, an endogenous peptide from the stomach, has anti-inflammatory and antioxidative effects in a wide range of tissues. However, the effect of ghrelin on the regulation of mucus secretion has not yet been studied in the human nasal mucosa. Therefore, we investigated the effects of ghrelin on lipopolysaccharide (LPS)/leptin-mediated MUC5AC expression and mechanisms involved in human nasal epithelial cells (HNEpCs). @*Methods@#. In HNEpCs, the effect and signaling pathways of ghrelin on LPS/leptin-induced MUC5AC expression were examined using reverse transcription polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassays, Western blotting, and immunofluorescence staining. @*Results@#. Growth hormone secretagogue receptor 1a (GHSR1a) was expressed in the HNEpCs. Ghrelin downregulated LPS/leptin-induced MUC5AC expression, which was abolished by D-Lys-3-growth hormone-releasing peptide 6 (D-Lys-3-GHRP-6). Ghrelin significantly inhibited LPS/leptin-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs). These ghrelin-mediated changes in MAPK activation were abolished by D-Lys-3-GHRP-6. These results showed that ghrelin inhibits LPS/leptin-induced MUC5AC overexpression by modulating the ERK1/2 and p38 MAPK pathways in HNEpCs. @*Conclusion@#. These findings suggest that ghrelin is a potential therapeutic agent for treating obesity-related inflammatory sinonasal diseases.

Tractional Retinal Detachment in Eyes with Vitreous Hemorrhage and Proliferative Diabetic Retinopathy and Posterior Vitreous Detachment in Fellow Eye

Purpose@#To predict the presence of tractional retinal detachment (TRD) in eyes with dense vitreous hemorrhage (VH) and proliferative diabetic retinopathy (PDR) by evaluating the status of posterior vitreous detachment (PVD) in fellow eyes using optical coherence tomography (OCT). @*Methods@#A total of 44 eyes from 22 patients who underwent vitrectomy due to dense VH with PDR were enrolled. Using OCT, the PVD status in the fellow eye was divided into two groups (incomplete and complete PVD). The incomplete PVD group included eyes without PVD and eyes with partial PVD. B-scan ultrasonography was performed on eyes with dense VH to evaluate the presence of TRD. Both OCT and B-scan images were reviewed by four ophthalmologists (two novices and two experienced), and the interobserver agreement was evaluated. @*Results@#There was a difference in the interobserver agreement regarding the presence of TRD in eyes with dense VH evaluated by B scan between novice and experienced ophthalmologists (novice, κ = 0.421 vs. experienced, κ = 0.814), although there was no difference between novice and experienced ophthalmologists in the interobserver agreement regarding the status of PVD in the fellow eye evaluated by OCT (novice, κ = 1.000 vs. experienced, κ = 1.000). All observed TRD during vitrectomy occurred in eyes with incomplete PVD in the fellow eye. Logistic regression analysis revealed a statistically significant relation between TRD and the age of the patient (odds ratio [OR], 0.874; p = 0.047), and between TRD and incomplete PVD in the fellow eye evaluated by OCT (OR, 13.904; p = 0.042). @*Conclusions@#Evaluation of the PVD status in the fellow eye using OCT may be a useful predictor for detecting the presence of TRD in eyes with dense VH and PDR.

Autologous Costal Cartilage Augmentation Technique for Treatment of Empty Nose Syndrome / 대한이비인후과학회지

Empty nose syndrome is a rare complication caused by excessive removal of normal tissues after nose surgery. The main symptoms of empty nose syndrome are paradoxical nasal obstruction, dryness, crust and dyspnea. Medical treatments such as irrigation, humidification, and ointment are not very effective, so surgical treatments to reconstruct the normal nasal cavity using implant materials are often considered. If the implant is not properly inserted, the symptoms persist and the implant must be removed again, resulting in the only donor site complications. Therefore, it is essential to treat the implant well and insert it precisely. Here we describe a surgical procedure to manage implant materials using autologous costal cartilage in the form of block, diced, and crushed cartilage for augmentation technique.

Orbital Apex Syndrome and Central Retinal Vein Occlusion after Blow-out Fracture Repair

Purpose@#To report a case of orbital apex syndrome and central retinal vein occlusion after blow-out fracture repair.Case summary: A 22-year-old man who underwent emergency re-operation in a department of plastic surgery due to pain, decreased visual acuity, and ophthalmoplegia in all direction after orbital blow-out fracture repair was referred to ophthalmologist on postoperative day 2 and there was no improvement in symptoms. He showed severe complications, including optic neuropathy and ophthalmoplegia in all direction, central retinal vein occlusion, and outer retinal disruption caused by orbital apex hemorrhage. Although we were concerned that it was too late, we started high dose steroid intravenous pulse treatment and the visual acuity, ophthalmoplegia, and retinal findings were improved. However, the optic atrophy and visual field defect did not. @*Conclusions@#After a complicated blow-out fracture repair in other department, if a patient shows severely decreased visual acuity or ocular movement limitation, a thorough and immediate ophthalmologic examination is recommended. During ophthalmologic examination, meticulous examination of the entire eye, including the retina, is required, in addition to general orbital complications. A relatively good prognosis can be expected through accurate cause analysis and appropriate treatment for the confirmed abnormal findings.

Aqueous Humor Cytokine Levels and Choroidal Thicknesses of Patients with Age‐related Macular Degeneration and Pachychoroid Neovasculopathy

Purpose@#We sought correlations between the subfoveal choroidal thickness (SCT) and changes in the levels of aqueous humor cytokines before and after anti‐vascular endothelial growth factor (anti‐VEGF) treatment of patients with neovascular age‐related macular degeneration (nAMD) and pachychoroid neovasculopathy. @*Methods@#We measured changes in the SCT and levels of aqueous humor cytokines (VEGF, soluble VEGF receptor‐2 [sVEGFR‐ 2], platelet‐derived growth factor [PDGF]‐AA, monocyte chemoattractant protein 1 [MCP‐1], interleukin [IL]‐6, and IL‐8) after anti‐ VEGF treatment of 11 eyes of 11 nAMD patients and nine eyes of nine pachychoroid neovasculopathy patients. The aqueous humor cytokine levels were compared between the two groups. @*Results@#After anti‐VEGF treatment, the aqueous levels of VEGF and PDGF‐AA decreased significantly, whereas that of sVEGFR‐2 increased. The amount of change in sVEGFR‐2 concentration before and after anti‐VEGF treatment correlated with the SCT and its change after treatment. nAMD patients with relatively thin SCTs and smaller SCT changes after anti‐VEGF treatment showed greater increases in sVEGFR‐2 levels following treatment. We found significant correlations among the MCP‐1, IL‐6, and IL‐8 levels in the nAMD group, and between the sVEGFR‐2 and MCP‐1, and MCP‐1 and PDGF‐AA, levels in the pachychoroid neovasculopathy group. @*Conclusions@#Patients with nAMD exhibited significant increases in aqueous sVEGFR‐2 levels following anti‐VEGF treatment and significant correlations among the levels of the inflammatory cytokines MCP‐1, IL‐6, and IL‐8, suggesting that angiogenic factors and inflammatory cytokines may affect the pathophysiologies of the two diseases differently.

Changes in Mucin Production in Human Airway Epithelial Cells After Exposure to Electronic Cigarette Vapor With or Without Nicotine

Objectives@#. The emergence of electronic cigarettes (e-cigarettes) has created new perceptions of the tobacco market. Unlike traditional tobacco, the greatest advantage of e-cigarettes is that they have less smell and are convenient and inexpensive. Most e-cigarette smokers believe that e-cigarette smoking is less harmful than traditional smoking. Information on the effects of e-cigarettes on human health is limited, and the issue remains controversial. @*Methods@#. We studied the effects of e-cigarette vapor on mucin (MUC5AC and MUC5B) and the change of MUC5AC and MUC5B from e-cigarette liquid with or without nicotine in respiratory epithelial cells. The effects of e-cigarette vapor with or without nicotine on mucin, along with the involved signaling pathways, were investigated using reverse transcriptase-polymerase chain reaction (PCR), real-time PCR, enzyme immunoassays, and immunoblot analysis with several specific inhibitors and small interfering RNA. @*Results@#. E-cigarette vapor with or without nicotine stimulated MUC5AC, but not MUC5B, expression in respiratory epithelial cells. In addition, we showed that e-cigarette vapor with and without nicotine induced MUC5AC expression via activation of the mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase [ERK] 1/2 and p38) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways in human airway epithelial cells. @*Conclusion@#. E-cigarette vapor with and with nicotine significantly increased MUC5AC expression in human airway epithelial cells.

Changes in Mucin Production in Human Airway Epithelial Cells After Exposure to Electronic Cigarette Vapor With or Without Nicotine

Objectives@#. The emergence of electronic cigarettes (e-cigarettes) has created new perceptions of the tobacco market. Unlike traditional tobacco, the greatest advantage of e-cigarettes is that they have less smell and are convenient and inexpensive. Most e-cigarette smokers believe that e-cigarette smoking is less harmful than traditional smoking. Information on the effects of e-cigarettes on human health is limited, and the issue remains controversial. @*Methods@#. We studied the effects of e-cigarette vapor on mucin (MUC5AC and MUC5B) and the change of MUC5AC and MUC5B from e-cigarette liquid with or without nicotine in respiratory epithelial cells. The effects of e-cigarette vapor with or without nicotine on mucin, along with the involved signaling pathways, were investigated using reverse transcriptase-polymerase chain reaction (PCR), real-time PCR, enzyme immunoassays, and immunoblot analysis with several specific inhibitors and small interfering RNA. @*Results@#. E-cigarette vapor with or without nicotine stimulated MUC5AC, but not MUC5B, expression in respiratory epithelial cells. In addition, we showed that e-cigarette vapor with and without nicotine induced MUC5AC expression via activation of the mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase [ERK] 1/2 and p38) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways in human airway epithelial cells. @*Conclusion@#. E-cigarette vapor with and with nicotine significantly increased MUC5AC expression in human airway epithelial cells.

Peroxiredoxin 2 Inhibits Lipopolysaccharide Induced Mucin Expression and Reactive Oxygen Species Production in Human Airway Epithelial Cells / 대한이비인후과학회지

Background and Objectives@#Peroxiredoxin (Prx) is an antioxidant enzyme involved in signaling pathway. Prx2 is the most abundant in mammalian gray matter neurons and has protective role under oxidative stress. MUC5AC and MUC5B are typical mucin genes in human airway epithelial cells. Even if free radicals play a key role in chronic respiratory inflammatory diseases, the effects of the Prx2 on mucin expression and oxidative stress are not clearly known. The purpose of this study is to investigate the effect of Prx2 on lipopolysaccharide (LPS)-induced MUC5AC/5B expression and reactive oxygen species (ROS) in human airway epithelial cells.Subjects and Method In NCI-H292 cells and human nasal epithelial cells, the effects of Prx2 on LPS-induced MUC5AC/5B expression and ROS production were investigated using reverse transcriptase-polymerase chain reaction, real-time polymerase chain reaction, enzyme linked immunosorbent assay (ELISA) and flow cytometry analysis. @*Results@#MUC5AC, MUC5B mRNA expression and protein production were increased by LPS. ROS production was also increased by LPS. Prx2 suppressed the LPS-induced MUC5AC mRNA expression and protein production as well as ROS production. However, Prx2 did not inhibit MUC5B mRNA expression and protein production. N-acetylcysteine, diphenyleneiodonium, and apocynin also inhibited LPS-induced ROS production. @*Conclusion@#These results may show that Prx2 suppresses LPS-induced MUC5AC expression via ROS in human airway epithelial cells.

Ginsenoside Rb1 Attenuates TGF-β1-Induced MUC4/5AC Expression and Epithelial-Mesenchymal Transition in Human Airway Epithelial Cells / 대한이비인후과학회지

Background and Objectives@#Ginsenoside Rb1 is the main metabolite of Panax ginseng. It is known to have many beneficial properties including anti-inflammatory, antitumoral and antioxidant effects. However, the therapeutic effects of ginenoside Rb1 on inflammatory airway diseases have not been elucidated. Therefore, we investigated the effects of ginsenoside Rb1 on the TGF-β1-induced mucin gene expression and epithelial-mesenchymal transition (EMT) in human airway epithelial cells.Materials and Method We evaluated the effects of ginsenoside Rb1 on the changes of MUC4, MUC5AC, occludin, claudin 4, claudin 18, neural (N)-cadherin, and epithelial (E)-cadherin expression by TGF-β1 in NCI-H292 cells using reverse, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and western blot. @*Results@#TGF-β1 significantly increased MUC4/5AC expression. Rb1 inhibited TGF-β1- induced MUC4/5AC expression. In addition, TGF-β1 significantly attenuated occludin, claudin 18, and E-cadherin expressions but induced claudin 4 and N-cadherin expressions. On the other hand, Rb1 reversed changes in the TGF-β1- mediated expressions of cell junction molecules. @*Conclusion@#These results suggest that ginsenoside Rb1 attenuates TGF-β1-induced MUC4/5AC expressions and EMT in the human airway epithelial cells. These findings are important data demonstrating the potential of ginsenoside Rb1 as a therapeutic agent for inflammatory airway diseases.

The Progression of SARS Coronavirus 2 (SARS-CoV2): Mutation in the Receptor Binding Domain of Spike Gene

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a positive-sense singlestranded RNA (+ssRNA) that causes coronavirus disease 2019 (COVID-19). The viral genome encodes twelve genes for viral replication and infection. The third open reading frame is the spike (S) gene that encodes for the spike glycoprotein interacting with specific cell surface receptor – angiotensin converting enzyme 2 (ACE2) – on the host cell membrane. Most recent studies identified a single point mutation in S gene. A single point mutation in S gene leading to an amino acid substitution at codon 614 from an aspartic acid 614 into glycine (D614G) resulted in greater infectivity compared to the wild type SARS-CoV2. We were interested in investigating the mutation region of S gene of SARS-CoV2 from Korean COVID-19 patients. New mutation sites were found in the critical receptor binding domain (RBD) of S gene, which is adjacent to the aforementioned D614G mutation residue. This specific sequence data demonstrated the active progression of SARS-CoV2 by mutations in the RBD of S gene.The sequence information of new mutations is critical to the development of recombinant SARS-CoV2 spike antigens, which may be required to improve and advance the strategy against a wide range of possible SARS-CoV2 mutations.

The Progression of SARS Coronavirus 2 (SARS-CoV2): Mutation in the Receptor Binding Domain of Spike Gene

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a positive-sense singlestranded RNA (+ssRNA) that causes coronavirus disease 2019 (COVID-19). The viral genome encodes twelve genes for viral replication and infection. The third open reading frame is the spike (S) gene that encodes for the spike glycoprotein interacting with specific cell surface receptor – angiotensin converting enzyme 2 (ACE2) – on the host cell membrane. Most recent studies identified a single point mutation in S gene. A single point mutation in S gene leading to an amino acid substitution at codon 614 from an aspartic acid 614 into glycine (D614G) resulted in greater infectivity compared to the wild type SARS-CoV2. We were interested in investigating the mutation region of S gene of SARS-CoV2 from Korean COVID-19 patients. New mutation sites were found in the critical receptor binding domain (RBD) of S gene, which is adjacent to the aforementioned D614G mutation residue. This specific sequence data demonstrated the active progression of SARS-CoV2 by mutations in the RBD of S gene.The sequence information of new mutations is critical to the development of recombinant SARS-CoV2 spike antigens, which may be required to improve and advance the strategy against a wide range of possible SARS-CoV2 mutations.

Effect of Tobacco-specific Nitrosamines on MUC5AC Expression in Human Airway Epithelial Cells

Background and Objectives@#Nicotine is oxidized into tobacco-specific nitrosamines (TSNAs; NAB, NAT, NNN, NNAL, NNK) at high temperature and high pressure. TSNAs are associated with airway diseases characterized by mucus hypersecretion as a major pathophysiologic phenomenon. The aim of study is to investigate the effect of TSNAs on mucin overexpression and its molecular mechanism in human airway epithelial cells.Materials and Method: The cytotoxicity of TSNAs was evaluated using EX-Cytox and inverted microscopy. The mRNA and protein levels of MUC5AC and MUC5B were measured using real-time PCR and ELISA. @*Results@#NAB, NNN, NNAL, and NNK did not affect cell viability. NAT did not affect cell viability up to a concentration of 100 μM in human airway epithelial cells. NAT, NNN, NNAL, and NNK significantly induced MUC5AC expression, but not MUC5B expression. NAB did not affect the expression of MUC5AC and MUC5B. Propranolol (a β-adrenergic receptor antagonist) inhibited NAT, NNN, NNAL, and NNK-induced MUC5AC expression, whereas α-bungarotoxin (an α7-nicotinic acetylcholine receptor antagonist) only inhibited NNN- and NNK-induced MUC5AC expression. @*Conclusion@#These results suggested that NAT, NNN, NNAL, and NNK induce MUC5AC expression through β-adrenergic receptor and/or α7-nicotinic acetylcholine receptor in human airway epithelial cells, which may be involved in mucus hypersecretion in inflammatory airway diseases.

Effect of Resolvin D1 and E1 on Mucin Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mucin is an important component of mucus that performs the first line of defense against inhaled pathogens and particles, lubrication of organs, and protection of airway. It is hyper-secreted in inflammatory airway diseases and is associated with morbidity and mortality of the affected patients. Resolvin, an autacoid of a specific lipid structure, exhibits anti-inflammatory property against inflammatory airway diseases although its effects on mucin secretion by human airway epithelial cells have not yet been demonstrated. In this regard, we investigated the effects of Resolvin on lipopolysaccharide (LPS)-induced mucin expression in human airway epithelial cells. MATERIALS AND METHOD: In mucin-producing human NCI-H292 epithelial cells, the effects and brief signaling pathways of Resolvin D1 (RvD1) and Resolvin E1 (RvE1) on the LPS-induced MUC4, MUC5AC, and MUC5B expression were investigated using reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot analysis. RESULTS: RvD1 attenuated LPS-induced MUC4, MUC5AC, and MUC5B mRNA expression and protein production in human NCI-H292 cells while RvE1 did not. RvD1 significantly blocked LPS-induced activated phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) and p38 MAPK and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) while RvE1 did not. CONCLUSION: These results suggest that RvD1 attenuates LPS-induced MUC4, MUC5AC, and MUC5B expressions via ERK1/2 MAPK, p38 MAPK, and NF-κB signaling pathways in airway epithelial cells. Therefore, RvD1 may modulate the control of mucus-hypersecretion in inflammatory airway diseases.

Inhibitory Effects of Protopanaxadiol on Lipopolysaccharide-Induced Reactive Oxygen Species Production and MUC5AC Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES@#MUC5AC is one of the major secretory mucin genes in the human airway epithelium. MUC5AC expression is increased by a variety of inflammatory mediators. Protopanaxadiol (PPD), one of the major active metabolites in ginseng, is known to have anti-inflammatory, antitumor and antioxidant properties. However, the effects of PPD on mucin secretion of airway epithelial cells still have not been reported. Therefore, the aim of this study is to investigate the effect of PPD on lipopolysaccharide (LPS)-induced MUC5AC expression in human airway epithelial cells. MATERIALS AND METHOD: In the mucin-producing human NCI-H292 airway epithelial cells, the effect of PPD on MUC5AC expression was investigated using reverse transcription-polymerase chain reaction and enzyme immunoassay after treated with LPS. N-acetylcysteine (NAC) as a reactive oxygen species (ROS) scavenger, and apocynin as a nicotinamide adenine dinucleotide phosphate oxidase inhibitor were used to compare the inhibitory effect of PPD on LPS-induced ROS production in human NCI-H292 cells. @*RESULTS@#LPS significantly increased MUC5AC mRNA expression and protein production. LPS also increased ROS production. PPD inhibited LPS-induced MUC5AC mRNA expression and protein production as well as ROS production. In addition, NAC and apocynin inhibited LPS-induced MUC5AC mRNA expression and protein production. @*CONCLUSION@#These results demonstrate that PPD inhibits LPS-induced MUC5AC expression via ROS in human airway epithelial cells and the inhibitory effect of PPD was similar to that of NAC and apocynin. These findings indicate that PPD may be a therapeutic agent for control of mucus secretion and oxidative stress in human airway epithelial cells.

Association of Retinal Artery Occlusion with Subclinical Coronary Artery Disease

BACKGROUND: To evaluate the association between retinal artery occlusion (RAO) and subclinical coronary artery disease (CAD). METHODS: We studied 41 patients with non-arteritic RAO without any history or symptoms of CAD, who had undergone coronary computed tomographic angiography (CCTA) for systemic atherosclerotic evaluation between 2007 and 2012. The age- and gender-matched control group comprised 4-fold subjects who were randomly selected from asymptomatic subjects who underwent CCTA during general health evaluation. Medical records and CCTA findings were compared between RAO patients and control groups. Multiple logistic regression analysis was carried out to assess the risk factors associated with CAD. RESULTS: Cardiovascular risk factors were not significantly different between RAO patients and control groups. RAO patients showed higher coronary artery calcium score than did control subjects (267.9 ± 674.9 vs. 120.2 ± 289.5). On CCTA, the prevalence of obstructive CAD (diameter stenosis ≥ 50%) in RAO patients was significantly higher than that in controls (29% vs. 15%; odds ratio [OR], 3.0). RAO patients demonstrated a significantly higher segment-involvement score (SIS) (2.6 ± 3.0 vs. 1.6 ± 2.4) and segment-stenosis score (SSS) (3.6 ± 4.8 vs. 2.0 ± 3.3) than did controls. After adjustment of associated factors, RAO showed significant association (OR, 3.0) with obstructive CAD and extensive CAD (SIS > 4: OR, 2.8; SSS > 8: OR, 3.4). CONCLUSION: Patients with RAO had a higher prevalence of subclinical obstructive CAD with a more extensive and heavier burden of coronary artery plaques than did age- and gender-matched controls. Physicians should understand the potential risk of CAD in RAO patients.

Endoplasmic Reticulum Stress Induces MUC5AC and MUC5B Expression in Human Nasal Airway Epithelial Cells

OBJECTIVES: Endoplasmic reticulum (ER) stress is known to be associated with inflammatory airway diseases, and three major transmembrane receptors: double-stranded RNA-activated protein kinase-like ER kinase, inositol requiring enzyme 1, and activating transcription factor 6 (ATF6) play important roles in ER stress-related proinflammatory signaling. However, the effects of ER stress and these three major signaling pathways on the regulation of the production of airway mucins in human nasal airway epithelial cells have not been elucidated. METHODS: In primary human nasal epithelial cells, the effect of tunicamycin (an ER stress inducer) and 4-phenylbutyric acid (4-PBA, ER stress inhibitor) on the expression of MUC5AC and MUC5B was investigated by reverse transcriptasepolymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and immunoblot analysis. Small interfering RNA (siRNA) transfection was used to identify the mechanisms involved. RESULTS: Tunicamycin increased the expressions of MUC5AC and MUC5B and the mRNA expressions of ER stress-related signaling molecules, including spliced X-box binding protein 1 (XBP-1), transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP), and ATF6. In addition, 4-PBA attenuated the tunicamycin-induced expressions of MUC5AC and MUC5B and the mRNA expressions of ER stress-related signaling molecules. Furthermore, siRNA knockdowns of XBP-1, CHOP, and ATF6 blocked the tunicamycin-induced mRNA expressions and glycoprotein productions of MUC5AC and MUC5B. CONCLUSION.: These results demonstrate that ER stress plays an important role in the regulation of MUC5AC and MUC5B via the activations of XBP-1, CHOP, and ATF6 in human nasal airway epithelial cells.

Inhibitory Effects of Protopanaxadiol on Lipopolysaccharide-Induced Reactive Oxygen Species Production and MUC5AC Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: MUC5AC is one of the major secretory mucin genes in the human airway epithelium. MUC5AC expression is increased by a variety of inflammatory mediators. Protopanaxadiol (PPD), one of the major active metabolites in ginseng, is known to have anti-inflammatory, antitumor and antioxidant properties. However, the effects of PPD on mucin secretion of airway epithelial cells still have not been reported. Therefore, the aim of this study is to investigate the effect of PPD on lipopolysaccharide (LPS)-induced MUC5AC expression in human airway epithelial cells. MATERIALS AND METHOD: In the mucin-producing human NCI-H292 airway epithelial cells, the effect of PPD on MUC5AC expression was investigated using reverse transcription-polymerase chain reaction and enzyme immunoassay after treated with LPS. N-acetylcysteine (NAC) as a reactive oxygen species (ROS) scavenger, and apocynin as a nicotinamide adenine dinucleotide phosphate oxidase inhibitor were used to compare the inhibitory effect of PPD on LPS-induced ROS production in human NCI-H292 cells. RESULTS: LPS significantly increased MUC5AC mRNA expression and protein production. LPS also increased ROS production. PPD inhibited LPS-induced MUC5AC mRNA expression and protein production as well as ROS production. In addition, NAC and apocynin inhibited LPS-induced MUC5AC mRNA expression and protein production. CONCLUSION: These results demonstrate that PPD inhibits LPS-induced MUC5AC expression via ROS in human airway epithelial cells and the inhibitory effect of PPD was similar to that of NAC and apocynin. These findings indicate that PPD may be a therapeutic agent for control of mucus secretion and oxidative stress in human airway epithelial cells.

Udenafil, a Phosphodiesterase 5 Inhibitor, Reduces Body Weight in High-Fat-Fed Mice

PURPOSE: High-fat (HF) feeding induces hypothalamic leptin resistance via the activation of toll-like receptor 4 (TLR4). TLR4 deficiency confers resistance to diet-induced obesity. Udenafil, an anti-impotence drug, inhibits TLR4 in airway epithelial cells in vitro. In this study, we evaluated whether udenafil suppressed the hypothalamic expression of TLR4 and reduced body weight. MATERIALS AND METHODS: The hypothalamic expression of TLR4, phosphodiesterase 5 (PDE5), nuclear factor-κB (NF-κB), and myeloid differentiation primary response gene 88 (Myd88) was analyzed by real-time polymerase chain reaction after treating mice for 2 days with udenafil (0, 12, 120, or 600 µg/d). Furthermore, the hypothalamic expression of TLR4, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY) was analyzed after 9 days' treatment with udenafil and/or leptin. We also measured body weight and food intake following 9 days of udenafil and/or leptin treatment in control- and HF-fed mice. RESULTS: Udenafil suppressed hypothalamic TLR4 mRNA expression dose-dependently. The changes were associated with decreased PDE5, NF-κB, and Myd88 expression. Udenafil treatment for 9 days reduced body weight and caloric intake in HF-fed mice. This may have been associated with the suppression of NPY expression that was elevated by HF feeding. POMC expression was not affected by udenafil. However, udenafil did not augment the effects of leptin on the reduction of body weight and caloric intake in HF-fed mice. CONCLUSIONS: These results suggested that udenafil reduced body weight by suppressing hypothalamic TLR4 mRNA expression in HF-fed mice and the combination effect of udenafil and leptin was additive rather than synergistic.