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1.
Curr Issues Mol Biol ; 46(6): 5712-5723, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38921013

RESUMO

Aspergillus fumigatus is commonly found in the airway and is associated with airway inflammatory diseases. Zinc oxide (ZO) is known to be an essential microelement that facilitates fungal survival, growth, and proliferation. This study aimed to investigate the impact of ZO on A. fumigatus-induced fungal sinusitis in rabbits. Twenty-eight New Zealand white rabbits were divided into four groups for this study. Group 1 (6 sides) was treated with intramaxillary phosphate buffer saline (PBS) served as the negative control, Group 2 (6 sides) received intramaxillary PBS and ZO, Group 3 (8 sides) was treated with intramaxillary A. fumigatus alone, and Group 4 (8 sides) treated with intramaxillary A. fumigatus with ZO. After 4 and 12 weeks, sinus mucosal cytokine and transcription factor expressions were determined. A histological analysis was performed to determine inflammatory cell infiltration, number of secretory cells, and mucosal thickness. Fungal biofilm formation was determined using confocal laser microscopy. The intramaxillary instillation of A. fumigatus conidia led to an increase in protein and mRNA expression of interleukin (IL)-1ß and IL-8 in the maxillary sinus mucosa. They were associated with mitogen-activated protein kinase and activator protein-1. Furthermore, intramaxillary instillation of fungal conidia resulted in significant enhancement of inflammatory cell infiltration, epithelial thickening, and fungal biofilm formation. However, intramaxillary ZO did not have a significant impact on A. fumigatus-induced cytokine protein and mRNA expression, and inflammatory cell infiltration and epithelial thickness in sinonasal mucosa. While intramaxillary instillation of A. fumigatus increased mucosal inflammation, cytokine production, and biofilm formation, the intramaxillary application of ZO did not have a significant influence on inflammation in the maxillary sinus mucosa.

2.
Sensors (Basel) ; 23(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36772693

RESUMO

The management of type 2 diabetes mellitus (T2DM) is generally not only focused on pharmacological therapy. Medical nutrition therapy is often forgotten by patients for several reasons, such as difficulty determining the right nutritional pattern for themselves, regulating their daily nutritional patterns, or even not heeding nutritional diet recommendations given by doctors. Management of nutritional therapy is one of the important efforts that can be made by diabetic patients to prevent an increase in the complexity of the disease. Setting a diet with proper nutrition will help patients manage a healthy diet. The development of Smart Plate Health to Eat is a technological innovation that helps patients and users know the type of food, weight, and nutrients contained in certain foods. This study involved 50 types of food with a total of 30,800 foods using the YOLOv5s algorithm, where the identification, measurement of weight, and nutrition of food were investigated using a Chenbo load cell weight sensor (1 kg), an HX711 weight weighing A/D module pressure sensor, and an IMX219-160 camera module (waveshare). The results of this study showed good identification accuracy in the analysis of four types of food: rice (58%), braised quail eggs in soy sauce (60%), spicy beef soup (62%), and dried radish (31%), with accuracy for weight and nutrition (100%).


Assuntos
Diabetes Mellitus Tipo 2 , Animais , Bovinos , Humanos , Dieta , Estado Nutricional , Nutrientes , Ovos
3.
Int J Mol Sci ; 24(3)2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36768687

RESUMO

Airborne fungi are ubiquitous in the environment and are commonly associated with airway inflammatory diseases. The innate immune defense system eliminates most inhaled fungi. However, some influence the development of chronic rhinosinusitis. Fungal CRS is thought of as not a common disease, and its incidence increases over time. Fungi are present in CRS patients and in healthy sinonasal mucosa. Although the immunological mechanisms have not been entirely explained, CRS patients may exhibit different immune responses than healthy people against airborne fungi. Fungi can induce Th1 and Th2 immune responses. In CRS, Th2-related immune responses against fungi are associated with pattern recognition receptors in nasal epithelial cells, the production of inflammatory cytokines and chemokines from nasal epithelial cells, and interaction with innate type 2 cells, lymphocytes, and inflammatory cells. Fungi also interact with neutrophils and eosinophils and induce neutrophil extracellular traps (NETs) and eosinophil extracellular traps (EETs). NETs and EETs are associated with antifungal properties and aggravation of chronic inflammation in CRS by releasing intracellular granule proteins. Fungal and bacterial biofilms are commonly found in CRS and may support chronic and recalcitrant CRS infection. The fungal-bacterial interaction in the sinonasal mucosa could affect the survival and virulence of fungi and bacteria and host immune responses. The interaction between the mycobiome and microbiome may also influence the host immune response, impacting local inflammation and chronicity. Although the exact immunopathologic role of fungi in the pathogenesis of CRS is not completely understood, they contribute to the development of sinonasal inflammatory responses in CRS.


Assuntos
Rinite , Sinusite , Humanos , Rinite/patologia , Sinusite/patologia , Mucosa Nasal/metabolismo , Inflamação/metabolismo , Fungos , Doença Crônica
4.
Int J Mol Sci ; 24(24)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38139091

RESUMO

Chronic rhinosinusitis (CRS) is characterized by inflammatory cell infiltration in the sinonasal mucosa. Eosinophil and neutrophil extracellular traps (EETs and NETs, respectively) are prominently found in CRS. This study aimed to investigate the effect of airborne fungi, Alternaria alternata and Aspergillus fumigatus, on EET and NET formation. Nasal epithelial cells, eosinophils, and neutrophils were isolated from eosinophilic CRS (ECRS), non-ECRS (NECRS), and healthy control. We determined eosinophil and neutrophil transepithelial migration after fungal treatment. We then determined the release of EETs and NETs by fungi using Sytox Green staining and determined the role of reactive oxygen species (ROS) using ROS inhibitors. We identified more abundant EETs and NETs in ECRS than in NECRS. A. alternata and A. fumigatus enhanced eosinophil and neutrophil transepithelial migration. A. fumigatus strongly induced EET and NET formation in CRS and, simultaneously, suppressed fungal metabolic activity. EET formation in CRS is associated with nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and NET formation with NADPH-oxidase and mitochondrial ROS. A. fumigatus, but not A. alternata, induced EET and NET formation, and peripheral blood eosinophils and neutrophils exhibited different immune responses against A. fumigatus following the inflammatory status of the host. Aspergillus-fumigatus-induced EET and NET formation plays a crucial role in CRS pathogenesis.


Assuntos
Armadilhas Extracelulares , Rinossinusite , Sinusite , Humanos , Neutrófilos/metabolismo , Armadilhas Extracelulares/metabolismo , Eosinófilos , Espécies Reativas de Oxigênio/metabolismo , NADP/metabolismo , Doença Crônica , Sinusite/metabolismo , Aspergillus , Aspergillus fumigatus , NADPH Oxidases/metabolismo
5.
Molecules ; 28(15)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37570665

RESUMO

Lidocaine, a local anesthetic, is known to possess anti-inflammatory properties. However, its clinical use is limited by inconveniences, such as its local synesthetic effects. This study evaluated lidocaine analogs designed and synthesized to overcome the disadvantages of lidocaine, having anti-inflammatory properties. Interleukin 5 (IL-5)-induced eosinophil activation and survival were evaluated using 36 lidocaine analogs with modified lidocaine structure on the aromatic or the acyl moiety or both. Eosinophil survival was evaluated using a CellTiter 96® aqueous cell proliferation assay kit. Superoxide production was determined using the superoxide dismutase-inhibitable reduction of cytochrome C method. Eosinophil cationic protein (ECP), IL-8, and transcription factor expression were determined using enzyme-linked immunosorbent assay. The platelet-activating factor (PAF)-induced migration assay was performed using a Transwell insert system. Compounds EI137 and EI341 inhibited IL-5-induced eosinophil survival and superoxide and ECP production in a concentration-dependent manner. These compounds also significantly reduced IL-8 production. Although compounds EI137 and EI341 significantly reduced phosphorylated ERK 1/2 expression, they did not influence other total and phosphorylated transcription factors. Moreover, 1000 µM of compound EI341 only inhibited PAF-induced migration of eosinophils. Lidocaine analogs EI137 and EI341 inhibited IL-5-mediated activation and survival of eosinophils. These compounds could be new therapeutic agents to treat eosinophilic inflammatory diseases.


Assuntos
Eosinófilos , Superóxidos , Superóxidos/metabolismo , Lidocaína/farmacologia , Interleucina-5/metabolismo , Interleucina-5/farmacologia , Interleucina-8/metabolismo , Fator de Ativação de Plaquetas/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo
6.
Int J Mol Sci ; 23(6)2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35328451

RESUMO

BACKGROUND: Asian sand dust (ASD) and Aspergillus fumigatus are known risk factors for airway mucosal inflammatory diseases. Bacterial and fungal biofilms commonly coexist in chronic rhinosinusitis and fungus balls. We evaluated the effects of ASD on the development of A. fumigatus biofilm formation on nasal epithelial cells. METHODS: Primary nasal epithelial cells were cultured with A. fumigatus conidia with or without ASD for 72 h. The production of interleukin (IL)-6, IL-8, and transforming growth factor (TGF)-ß1 from nasal epithelial cells was determined by the enzyme-linked immunosorbent assay. The effects of ASD on A. fumigatus biofilm formation were determined using crystal violet, concanavalin A, safranin staining, and confocal scanning laser microscopy. RESULTS: ASD and A. fumigatus significantly enhanced the production of IL-6 and IL-8 from nasal epithelial cells. By coculturing A. fumigatus with ASD, the dry weight and safranin staining of the fungal biofilms significantly increased in a time-dependent manner. However, the increased level of crystal violet and concanavalin A stain decreased after 72 h of incubation. CONCLUSIONS: ASD and A. fumigatus induced the production of inflammatory chemical mediators from nasal epithelial cells. The exposure of A. fumigatus to ASD enhanced the formation of biofilms. The coexistence of ASD and A. fumigatus may increase the development of fungal biofilms and fungal inflammatory diseases in the sinonasal mucosa.


Assuntos
Aspergillus fumigatus , Areia , Aspergillus fumigatus/metabolismo , Biofilmes , Concanavalina A/farmacologia , Poeira , Células Epiteliais/metabolismo , Violeta Genciana/metabolismo , Violeta Genciana/farmacologia , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Mucosa Nasal/metabolismo
7.
Int J Mol Sci ; 23(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36362100

RESUMO

Chronic rhinosinusitis (CRS) is a diverse chronic inflammatory disease of the sinonasal mucosa. CRS manifests itself in a variety of clinical and immunologic patterns. The histological hallmark of eosinophilic CRS (ECRS) is eosinophil infiltration. ECRS is associated with severe disease severity, increased comorbidity, and a higher recurrence rate, as well as thick mucus production. Eosinophils play an important role in these ECRS clinical characteristics. Eosinophils are multipotential effector cells that contribute to host defense against nonphagocytable pathogens, as well as allergic and nonallergic inflammatory diseases. Eosinophils interact with Staphylococcus aureus, Staphylococcal enterotoxin B, and fungi, all of which were found in the tissue of CRS patients. These interactions activate Th2 immune responses in the sinonasal mucosa and exacerbate local inflammation. Activated eosinophils were discovered not only in the tissue but also in the sinonasal cavity secretion. Eosinophil extracellular traps (EETs) are extracellular microbes trapping and killing structures found in the secretions of CRS patients with intact granule protein and filamentous chromatic structures. At the same time, EET has a negative effect by causing an epithelial barrier defect. Eosinophils also influence the local tissue microenvironment by exchanging signals with other immune cells and structural cells. As a result, eosinophils are multifaceted leukocytes that contribute to various physiologic and pathologic processes of the upper respiratory mucosal immune system. The goal of this review is to summarize recent research on the immunopathologic properties and immunologic role of eosinophils in CRS.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Eosinófilos , Pólipos Nasais/metabolismo , Sinusite/complicações , Contagem de Leucócitos , Doença Crônica
8.
Molecules ; 27(9)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35565992

RESUMO

Chronic rhinosinusitis (CRS) is characterized by chronic inflammation of the sinonasal mucosa with epithelial dedifferentiation toward the mesenchymal phenotype, known as the epithelial-mesenchymal transition (EMT). Asian sand dust (ASD) can induce nasal mucosal inflammation and cause the development of EMT. Korean red ginseng (KRG) and ginsenoside Rg3 have been used as traditional herbal medicines to treat various diseases. The aim of this study was to investigate their effect on ASD-induced EMT in nasal epithelial cells. Primary nasal epithelial cells were incubated with ASD with or without KRG or Rg3, and the production of transforming growth factor-ß1 (TGF-ß1) and interleukin (IL)-8 was measured. EMT markers were determined by RT-PCR, Western blot analysis, and confocal microscopy, and transcription factor expression by Western blot analysis. The effect on cell migration was evaluated using the wound scratch assay. Results showed ASD-induced TGF-ß1 production, downregulation of E-cadherin, and upregulation of fibronectin in nasal epithelial cells. KRG and Rg3 suppressed TGF-ß1 production (31.7% to 43.1%), upregulated the expression of E-cadherin (26.4% to 88.3% in mRNA), and downregulated that of fibronectin (14.2% to 46.2% in mRNA and 52.3% to 70.2% in protein). In addition, they suppressed the ASD-induced phosphorylation of ERK, p38, and mTOR, as well as inhibiting the ASD-induced migration of nasal epithelial cells (25.2% to 41.5%). The results of this study demonstrate that KRG and Rg3 inhibit ASD-induced EMT by suppressing the activation of ERK, p38, and mTOR signaling pathways in nasal epithelial cells.


Assuntos
Transição Epitelial-Mesenquimal , Panax , Caderinas/metabolismo , Movimento Celular , Poeira , Células Epiteliais , Fibronectinas/metabolismo , Ginsenosídeos , Humanos , Inflamação/metabolismo , Panax/metabolismo , RNA Mensageiro/metabolismo , Areia , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
9.
J Korean Med Sci ; 36(40): e264, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34664801

RESUMO

BACKGROUND: Endoscopic sinus surgery (ESS) is the mainstay treatment for refractory chronic rhinosinusitis (CRS). Since various factors may contribute to the surgical outcome, it is challenging for physicians to predict surgical outcomes. The aim of study was to analyze the prognostic factors of postoperative outcomes and to establish the prediction model with the risk factors that impact the postoperative outcomes. METHODS: Medical records of CRS patients who underwent ESS at 9 institutions in 2005, 2010, and 2016 were retrospectively reviewed. We classified the patients into 2 groups based on postoperative objective endoscopic outcomes. Demographics, nose-specific symptoms, olfactory function, eosinophil counts in blood (EoB) and nasal tissue (EoT), and Lund-Mackay CT score (LMS) were collected. Univariate and multivariate analyses were performed and established a prediction equation for postoperative endoscopic objective outcomes. RESULTS: In total (n = 1,249), 27.0% were not satisfied under postoperative endoscopic examination. Of 10 variables, LMS (> 5), sinus dominancy (maxillary sinus and ethmoid sinus), EoB (> 210), and EoT (> 100) were statistically significant in univariate analysis (P < 0.05, all). In multivariate analysis, EoT (> 100) and LMS (> 5) were significantly associated with poor postoperative outcome. Furthermore, 5 significant variables were employed to establish the risk model of postoperative outcomes and P (the value of prediction probability) = 1 / (1 + exp [-0.392 + 1.088 × EoT (> 100) + 0.123 × mean LMS (> 5) - 0.366 × sinus dominancy (maxillary) + 0.064 × sinus dominancy (similar) + 0.200 × EoB (4%) + 0.344 × EoB (> 210)] was developed. CONCLUSION: Tissue eosinophil count and radiographic severity predispose to a poorer outcome of ESS and the risk model established may be helpful to predict postoperative outcomes of ESS.


Assuntos
Rinite/cirurgia , Sinusite/cirurgia , Adulto , Doença Crônica , Endoscopia , Eosinófilos/citologia , Seio Etmoidal/patologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Período Pós-Operatório , Prognóstico , República da Coreia , Estudos Retrospectivos , Rinite/patologia , Fatores de Risco , Índice de Gravidade de Doença , Sinusite/patologia , Resultado do Tratamento
10.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916022

RESUMO

Korean Red ginseng (KRG), commonly used in traditional medicine, has anti-inflammatory, anti- oxidative, and anti-tumorigenic properties. Asian sand dust (ASD) is known to aggravate upper and lower airway inflammatory responses. BEAS-2B cells were exposed to ASD with or without KRG or ginsenoside Rg3. Mucin 5AC (MUC5AC), MUC5B, and MUC8 mRNA and protein expression levels were determined using quantitative RT-PCR and enzyme-linked immunosorbent assay. Nuclear factor kappa B (NF-κB), activator protein 1, and mitogen-activated protein kinase expression and activity were determined using western blot analysis. ASD induced MUC5AC, MUC5B, and MUC8 mRNA and protein expression in BEAS-2B cells, which was significantly inhibited by KRG and Rg3. Although ASD-induced mucin expression was associated with NF-κB and p38 mitogen-activated protein kinase (MAPK) activity, KRG and Rg3 significantly suppressed only ASD-induced NF-κB expression and activity. KRG and Rg3 inhibited ASD-induced mucin gene expression and protein production from bronchial epithelial cells. These results suggest that KRG and Rg3 have potential for treating mucus-producing airway inflammatory diseases.


Assuntos
Poeira , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Ginsenosídeos/farmacologia , Mucinas/genética , Panax/química , Areia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ginsenosídeos/química , Humanos , Estrutura Molecular , Mucina-5AC/biossíntese , Mucina-5AC/genética , Mucina-5B/biossíntese , Mucina-5B/genética , Mucinas/biossíntese , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo
11.
Eur Arch Otorhinolaryngol ; 277(3): 761-765, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31781838

RESUMO

PURPOSE: Fungus ball (FB) is the most common type of fungal rhinosinusitis and the prevalence of FB has increased over the past 10 years. The aim of this study was to compare the clinical characteristics of Korean adult patients with FB and chronic rhinosinusitis (CRS) without FB. METHODS: We retrospectively analyzed data on 1362 patients (147 FB and 1215 CRS) who underwent endoscopic sinus surgery at nine Korean medical centers in 2005, 2010, and 2016. We evaluated the prevalence of FB and compared the clinical characteristics of FB and CRS. Medical records, computed tomography (CT) findings, atopic status, concomitant diseases, tissue, and blood eosinophil count were assessed. RESULTS: The prevalence of FB was significantly higher in 2016 (15.9%) than in the other years (7.8% in 2005 and 7.5% in 2010). The FB patients were more likely to be female, older, have unilateral disease and less likely to have allergy compared to the CRS patients. The most common main complaint related to CRS and FB was nasal obstruction. CT determined that unilateral disease and maxillary sinus dominancy were common in patients with FB. The incidence of concomitant diseases was much higher in FB, with lower tissue and blood eosinophilia. CONCLUSION: FB is commonly encountered in older women with the increased prevalence. FB had a different clinical presentation, radiological findings, and prognosis than CRS. Further studies are needed to understand the pathophysiologic mechanisms underlying the development of FB.


Assuntos
Micoses/diagnóstico , Procedimentos Cirúrgicos Nasais/métodos , Seios Paranasais/cirurgia , Rinite/diagnóstico , Sinusite/diagnóstico , Adulto , Idoso , Doença Crônica , Endoscopia , Feminino , Humanos , Hipersensibilidade/complicações , Hipersensibilidade/diagnóstico , Masculino , Pessoa de Meia-Idade , Micoses/epidemiologia , Micoses/cirurgia , Seios Paranasais/microbiologia , Prevalência , República da Coreia/epidemiologia , Estudos Retrospectivos , Rinite/cirurgia , Sinusite/cirurgia , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
12.
Int J Mol Sci ; 21(8)2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32294933

RESUMO

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation. Airborne allergens are associated with upper and lower airway inflammatory disease. We investigated the effects of airborne allergen stimulation in the nasal epithelial cells and their effect on the peripheral blood mononuclear cells' (PBMCs) Th immune polarization. Interleukin (IL)-10, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels were determined using the enzyme-linked immunosorbent assay (ELISA) in nasal polyp tissues. Cultured primary nasal epithelial cells were stimulated with Alternaria alternata, Aspergillus fumigatus, Dermatophagoides pteronyssinus (DP), and Dermatophagoides farina (DF) for 48 hours. IL-6, IL-25, IL-33, and TSLP production were measured by ELISA, and the nuclear factor-κB (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinase (MAPK) expression were determined by western blot analyses. PBMCs were cultured with nasal epithelial cell-conditioned media (NECM), and IL-5, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured. Innate lymphoid type2 cells (ILC2) were analyzed with flowcytometry. IL-25, IL-33, and TSLP levels were significantly higher in eosinophilic nasal polyps. Alternaria, DP, and DF enhanced IL-33 and TSLP production from the nasal epithelial cells through the NF-κB, AP-1, and MAPK pathway. NECM induced IL-5, IFN-γ, and TNF-α production from PBMCs, without increasing ILC2 expression. Alternaria and house dust mites enhanced the chemical mediator production from nasal epithelial cells and these allergens may induce not only Th2 inflammatory responses but also Th1 inflammatory responses in the nasal mucosa.


Assuntos
Alternaria/imunologia , Mucosa Nasal/imunologia , Pyroglyphidae/imunologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Citocinas/metabolismo , Suscetibilidade a Doenças/imunologia , Humanos , Imunidade Inata , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Mucosa Nasal/metabolismo , Rinite/etiologia , Rinite/metabolismo , Rinite/patologia , Sinusite/etiologia , Sinusite/metabolismo , Sinusite/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th1/metabolismo , Células Th2/metabolismo
13.
Molecules ; 25(19)2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33023110

RESUMO

The present study aims to investigate the immunomodulatory effects of essential oil from Chamaecyparis obtusa (EOCO) in an ovalbumin (OVA)-induced allergic rhinitis (AR) mouse model. BALB/c mice were intraperitoneally sensitized and stimulated with OVA. From day 22 to 35, 0.01% and 0.1% ECOC was intranasally administered 1 h before OVA stimulation. Nasal symptoms, as well as serum total and OVA-specific immunoglobulin (Ig) E levels, were measured. Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and their production by activated splenocytes were measured. Histological changes in the sinonasal mucosa were evaluated through hematoxylin and eosin and periodic acid-Schiff staining procedure. Th cytokines and their transcription factor mRNA expressions were determined using reverse-transcription polymerase chain reaction. Intranasal EOCO administration significantly suppressed allergic symptoms, OVA-specific IgE level, sinonasal mucosal inflammatory cell infiltration, and mucus-producing periodic acid-Schiff (PAS) positive cell count. EOCO also significantly inhibited IL-4, IL-10, and TNF-α levels in NLF and activated splenocytes. Th2 and Treg related cytokines and their transcription factors in sinonasal mucosa were significantly suppressed through intransal EOCO instillation. In conclusion, repetitive EOCO intranasal instillation showed anti-inflammatory and anti-allergic effects by suppressing nasal symptoms and inhibiting the production and expression of inflammatory mediators in the OVA-induced AR mouse model.


Assuntos
Chamaecyparis/química , Fatores Imunológicos/uso terapêutico , Óleos Voláteis/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Animais , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Fatores Imunológicos/farmacologia , Mediadores da Inflamação/metabolismo , Camundongos Endogâmicos BALB C , Líquido da Lavagem Nasal , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Óleos Voláteis/farmacologia , Ovalbumina/imunologia , Rinite Alérgica/sangue , Baço/patologia , Fatores de Transcrição/metabolismo
14.
Bioconjug Chem ; 29(5): 1669-1676, 2018 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-29578690

RESUMO

Mitochondria-specific delivery methods offer a valuable tool for studying mitochondria-related diseases and provide breakthroughs in therapeutic development. Although several small-molecule and peptide-based transporters have been developed, peptoids, proteolysis-resistant peptidomimetics, are a promising alternative to current approaches. We designed a series of amphipathic peptoids and evaluated their cellular uptake and mitochondrial localization. Two peptoids with cyclohexyl residues demonstrated highly efficient cell penetration and mitochondrial localization without significant adverse effects on the cells and mitochondria. These mitochondria-targeting peptoids could facilitate the selective and robust targeted delivery of bioactive compounds, such as drugs, antioxidants, and photosensitizers, with minimal off-target effects.


Assuntos
Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos , Mitocôndrias/metabolismo , Peptoides/metabolismo , Linhagem Celular , Portadores de Fármacos/efeitos adversos , Portadores de Fármacos/análise , Células HeLa , Humanos , Mitocôndrias/efeitos dos fármacos , Doenças Mitocondriais/tratamento farmacológico , Doenças Mitocondriais/metabolismo , Peptoides/efeitos adversos , Peptoides/análise
15.
Psychosom Med ; 80(2): 193-199, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29189598

RESUMO

OBJECTIVE: Patients with sleep-related breathing disorders are known to have more severe psychiatric symptoms than good sleepers. The aim of this study was to compare the psychiatric symptoms of participants with obstructive sleep apnea (OSA), those with simple snoring (SS), and normal controls (NC). METHODS: A total of 386 participants (260 with OSA, 75 with SS, and 51 NC) completed self-report questionnaires including the Symptoms Checklist 90-Revised and underwent nocturnal polysomnography. The scores of nine primary symptom dimensions and three global distress indices of the Symptoms Checklist 90-Revised were compared among the three groups, adjusting for age, sex, and body mass index. RESULTS: Participants with suspected OSA (OSA + SS) reported more severe psychiatric symptoms than the NC group. Compared with the participants with OSA, those with SS manifested more severe obsessive-compulsive (1.4 (1.0) versus 1.1 (0.7), p = .008) and depressive (1.2 (1.2) versus 0.8 (0.8), p = .031) symptoms and higher Global Severity Index (1.0 (0.9) versus 0.7 (0.6), p = .039) and Positive Symptom Distress Index (2.0 (0.8) versus 1.7 (0.6), p = .009). Only higher Pittsburgh Sleep Quality Index values predicted higher Global Severity Index (B = 0.11, p = .041) and Positive Symptom Distress Index (B = 0.46, p = .007) in suspected OSA participants. CONCLUSIONS: This study found that individuals with suspected OSA experienced more severe psychiatric symptoms than NCs and that psychiatric symptoms were more severe in the SS group than in the OSA group. The psychiatric symptoms of suspected OSA patients were associated with subjective sleep quality rather than with the apnea-hypopnea index.


Assuntos
Sintomas Comportamentais/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Ronco/epidemiologia , Adulto , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , República da Coreia/epidemiologia
16.
Sleep Breath ; 21(4): 885-892, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28455734

RESUMO

PURPOSE: This study developed formulas to predict obstructive sleep apnea (OSA) and the Apnea-Hypopnea Index (AHI) in Korean patients with suspected OSA using clinical, anthropometric, and cephalometric variables. METHODS: We evaluated relevant variables in 285 subjects with suspected OSA. These included demographic characteristics, sleep-related symptoms, medical history, clinical scales, anthropometric measurements including facial surface measurements, and cephalometric measurements. All participants underwent full-night laboratory polysomnography. The prediction formula for the probability of OSA was created by logistic regression analysis and confirmed by the bootstrap resampling technique. The formula for predicting the AHI was developed using multiple linear regression analysis. RESULTS: The probability of having OSA was as follows: p = 1 / (1 + exponential (exp)-f ), where f = -16.508 + 1.445 × loudness of snoring 4 + 0.485 × loudness of snoring 3 + 0.078 × waist circumference + 0.209 × subnasale-to-stomion distance + 0.183 × thickness of the uvula (UTH) supine + 0.041 × age. The AHI prediction formula was as follows: -112.606 + 3.516 × body mass index + 0.683 × mandibular plane-hyoid supine + 10.915 × loudness of snoring 4 + 6.933 × loudness of snoring 3 + 1.297 × UTH supine + 0.272 × age. CONCLUSION: This is the first study to establish formulas to predict OSA and the AHI in Koreans with suspected OSA using cephalometric and other variables. These results will contribute to prioritizing the order in which patients with suspected OSA are referred for polysomnography.


Assuntos
Antropometria , Cefalometria , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Apneia Obstrutiva do Sono/complicações , Ronco/complicações , Adulto Jovem
17.
Sleep Breath ; 21(2): 369-375, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27815846

RESUMO

PURPOSE: The relationship between the severity of the apnea-hypopnea index (AHI) and the quality of life (QOL) in patients with obstructive sleep apnea (OSA) has been inconsistent in previous studies. This study aimed to identify the core factor associated with the QOL of suspected OSA patients and to compare the QOL of subjects with OSA and simple snoring (SS). METHODS: Two hundred eighty-five subjects who were clinically suspected to have OSA underwent nocturnal polysomnography (PSG) and completed self-report questionnaires including the World Health Organization Quality of Life Short Form (WHOQOL-BREF) and the Pittsburgh Sleep Quality Index (PSQI). The effects of the clinical and PSG variables on the QOL score were analyzed using multiple stepwise regression analyses, and the QOL of OSA and SS groups was compared. RESULTS: In correlation analyses, the most significant factor that correlated with the QOL of the subjects was the PSQI total score (p < 0.001), while the AHI was not related to the WHOQOL-BREF total score. In multiple linear regression analysis, the PSQI total score was the most significant factor associated with the QOL of participants (p < 0.001). The mean score of the WHOQOL-BREF did not differ significantly between the OSA group and the SS group. CONCLUSION: This study suggests that the main factor affecting the QOL of suspected OSA subjects is their subjective sleep quality. We therefore conclude that patients with OSA symptoms estimate their QOL based on their subjective sleep perception rather than AHI.


Assuntos
Atitude Frente a Saúde , Polissonografia , Qualidade de Vida/psicologia , Apneia Obstrutiva do Sono/psicologia , Higiene do Sono , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/diagnóstico , Estatística como Assunto , Inquéritos e Questionários
18.
Ann Allergy Asthma Immunol ; 116(6): 559-64, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27156749

RESUMO

BACKGROUND: Eosinophils and fibroblasts are known to play major roles in the pathogenesis of nasal polyps. Fungi are commonly found in nasal secretion and are associated with airway inflammation. OBJECTIVE: To investigate whether activated eosinophils by airborne fungi can influence the production of extracellular matrix (ECM) from nasal fibroblasts. METHODS: Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria or Aspergillus, respectively, for 24 hours and ECM messenger RNA (mRNA) and protein expressions were measured. Eosinophils isolated from healthy volunteers were stimulated with Alternaria or Aspergillus for 4 hours then superoxide, eosinophil peroxidase, and transforming growth factor ß1 were measured. Then activated eosinophils were cocultured with nasal fibroblasts for 24 hours, and ECM mRNA expressions were measured. RESULTS: Alternaria strongly enhanced ECM mRNA expression and protein production from nasal fibroblasts. Alternaria also induced the production of superoxide, eosinophil peroxidase, and transforming growth factor ß1 from eosinophils, and activated eosinophils enhanced ECM mRNA expression when they were cocultured without the Transwell insert system. CONCLUSION: Eosinophils activated with Alternaria enhanced ECM mRNA expression from nasal polyp fibroblasts. Alternaria plays an important role in tissue fibrosis in the pathogenesis of nasal polyps by directly or indirectly influencing the production of ECM from nasal fibroblasts.


Assuntos
Alternaria , Eosinófilos/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Actinas/metabolismo , Aspergillus , Células Cultivadas , Técnicas de Cocultura , Peroxidase de Eosinófilo/metabolismo , Fibronectinas/metabolismo , Humanos , Pólipos Nasais , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Conchas Nasais
19.
Biol Pharm Bull ; 37(8): 1295-300, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25087951

RESUMO

Bee venom (BV) has been used as an anti-inflammatory and immune modulating agent in Oriental medicine. This study used a mouse model to investigate the anti-allergic effect of BV, which is used in the treatment of various inflammatory diseases in traditional medicine. BV was obtained from the National Institute of Agricultural Science and Technology of Korea. Female BALB/C mice were sensitized by intraperitoneal injection of ovalbumin (OVA). BV was administered nasally prior to the intranasal instillation of OVA. Allergic behavior, serum OVA-specific immunoglobulin E (IgE), interleukin (IL)-4, IL-10, and interferon-gamma (INF-γ) levels in nasal lavage fluid were measured. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate histological change. BV attenuated nasal symptoms and inhibited the production of OVA-specific IgE and IL-4 in sensitized mice. The degree of inflammatory cell infiltration and goblet cell hyperplasia was attenuated by BV. Thus, BV effectively reduced allergic inflammation in a mouse model of allergic rhinitis, suggesting its potential as a useful therapeutic agent to treat allergic rhinitis.


Assuntos
Antialérgicos/uso terapêutico , Venenos de Abelha/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Alérgenos/imunologia , Animais , Antialérgicos/farmacologia , Venenos de Abelha/farmacologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Camundongos Endogâmicos BALB C , Mucinas/imunologia , NF-kappa B/imunologia , Líquido da Lavagem Nasal/imunologia , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Ovalbumina/imunologia , Rinite Alérgica/sangue , Rinite Alérgica/imunologia , Fator de Transcrição AP-1/imunologia
20.
Biomedicines ; 12(9)2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39335479

RESUMO

Allergic rhinitis (AR) is a common chronic disease that significantly impacts the quality of life. Lidocaine is known to have anti-inflammatory and immunomodulatory effects. This study evaluated the effect of lidocaine analogs in a Dermatophagoides pteronyssinus (DP)-induced AR mouse model. An AR model was developed using BALB/c mice via intraperitoneal sensitization with DP and intranasal challenge with DP. One hour before stimulation with DP, lidocaine analogs, EI137 and EI341 (at a dose of 0.5 or 5 ug/g), were administered intranasally. Nasal symptoms and serum total IgE, interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels were evaluated. Reverse-transcription polymerase chain reaction was used to determine IL-4, IL-10, and IFN-γ, as well as the expression of their mRNA transcription factors in the sinonasal mucosa. Histologic changes were evaluated using hematoxylin and eosin and periodic acid-Schiff staining. The DP-induced AR mouse model had increased serum levels of total IgE and cytokines. EI137 and EI341 significantly suppressed the levels of total IgE, IL-4, and TNF-α. Intranasal instillation of EI137 and EI341 significantly inhibited IL-4, IL-10, and IFN-γ mRNA expression, as well as inflammatory cells and mucus-producing goblet cells. Lidocaine analogs also suppressed DP-stimulated IL-4, IFN-γ, and IFN-γ production by splenocytes. Intranasal instillation of EI137 and EI341 exhibited anti-allergic and anti-inflammatory effects, influenced by Th1 and Th2 inflammatory cytokines. These lidocaine analogs suppressed DP-induced sinonasal mucosal inflammation, inflammatory cell infiltration, and mucus hypersecretion.

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