Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 19 de 19
Filter
1.
Cytokine ; 174: 156439, 2024 02.
Article in English | MEDLINE | ID: mdl-38134557

ABSTRACT

Neuregulin (NRG)-1 plays fundamental roles in several organ systems after binding to its receptors, ErbB2 and ErbB4. This study examines the role of NRG-1 in atopic dermatitis (AD), a chronic skin disease that causes dryness, pruritus, and inflammation. In mice administered Der p 38, the skin presents AD-like symptoms including filaggrin downregulation and infiltration of neutrophils and eosinophils. Noticeably, there is an increased expression of NRG-1, ErbB2, and ErbB4 in the skin. Upregulation of these proteins is significantly correlated to the clinical skin severity score. In human keratinocyte HaCaT cells, exposure to Der p 38 decreased filaggrin expression, and NRG-1 alone had no effect on the expression. However, co-treatment of Der p 38 with NRG-1 enhanced the filaggrin expression decreased by Der p 38. Pre-treatment with AG879 (an ErbB2 inhibitor) or ErbB4 siRNA blocked the recovery of filaggrin expression in the cells after co-treatment with Der p 38 and NRG-1. Der p 38 treatment enhanced the secretion of interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1). Co-treatment of Der p 38 with NRG-1 lowered the cytokine secretion increased by Der p 38, although NRG-1 alone was not effective on cytokine alteration. Neutrophil apoptosis was not altered by NRG-1 or supernatants of cells treated with NRG-1, but the cell supernatants co-treated with Der p 38 and NRG-1 blocked the anti-apoptotic effects of Der p 38-treated supernatants on neutrophils, which was involved in the activation of caspase 9 and caspase 3. Taken together, we determined that NRG-1 has anti-inflammatory effects in AD triggered by Der p 38. These results will pave the way to understanding the functions of NRG-1 and in the future development of AD treatment.


Subject(s)
Dermatitis, Atopic , Mice , Animals , Humans , Dermatitis, Atopic/genetics , Filaggrin Proteins , Neuregulin-1/pharmacology , Neuregulin-1/metabolism , Neuregulin-1/therapeutic use , Keratinocytes/metabolism , Skin/metabolism , Cytokines/metabolism , Receptor, ErbB-4/metabolism , Receptor, ErbB-4/pharmacology , Anti-Inflammatory Agents/pharmacology
2.
Sci Rep ; 13(1): 11529, 2023 07 17.
Article in English | MEDLINE | ID: mdl-37460621

ABSTRACT

This study aims to improve Korean male soldiers' mission performance and protect them from safety accidents by establishing an optimal sizing system that considers the fit of tactical gloves and production and supply efficiency. First, the wearing condition of tactical gloves was investigated through in-depth interviews and surveys. The optimal glove fit and loss coefficient ratio was then analyzed through a glove size selection experiment. Finally, the sizing system was optimized and verified by comparing the coverage rate to the current sizing system. The empirically derived loss coefficient ratio was 0.075, and the optimal sizing system for tactical gloves was S-hand length: 168 mm, hand width: 81 mm, M-hand length: 177 mm, hand width: 83 mm, L-hand length: 184 mm, hand width: 86 mm, XL-hand length: 191 mm, and hand width: 89 mm. The coverage rate of the optimal sizing system proposed in this study was 86.4%, showing an improvement of approximately 21.1% compared to the current sizing system (65.3%). In conclusion, the optimal sizing system for tactical gloves proposed in this study can realistically solve current sizing issues, as it improved the coverage rate by 21.1% without incurring additional costs for production or hindering the supply efficiency.


Subject(s)
Gloves, Protective , Military Personnel , Humans , Male , Asian People , Hand , Body Weights and Measures
3.
Sensors (Basel) ; 23(2)2023 Jan 09.
Article in English | MEDLINE | ID: mdl-36679566

ABSTRACT

To extract the phase information from multiple receivers, the conventional sound source localization system involves substantial complexity in software and hardware. Along with the algorithm complexity, the dedicated communication channel and individual analog-to-digital conversions prevent an increase in the system's capability due to feasibility. The previous study suggested and verified the single-channel sound source localization system, which aggregates the receivers on the single analog network for the single digital converter. This paper proposes the improved algorithm for the single-channel sound source localization system based on the Gaussian process regression with the novel feature extraction method. The proposed system consists of three computational stages: homomorphic deconvolution, feature extraction, and Gaussian process regression in cascade. The individual stages represent time delay extraction, data arrangement, and machine prediction, respectively. The optimal receiver configuration for the three-receiver structure is derived from the novel similarity matrix analysis based on the time delay pattern diversity. The simulations and experiments present precise predictions with proper model order and ensemble average length. The nonparametric method, with the rational quadratic kernel, shows consistent performance on trained angles. The Steiglitz-McBride model with the exponential kernel delivers the best predictions for trained and untrained angles with low bias and low variance in statistics.


Subject(s)
Software , Sound Localization , Algorithms
4.
Sci Rep ; 12(1): 13828, 2022 08 15.
Article in English | MEDLINE | ID: mdl-35970861

ABSTRACT

Childhood to adolescence is an accelerated growth period, and genetic features can influence differences of individual growth patterns. In this study, we examined the genetic basis of early age facial growth (EAFG) patterns. Facial shape phenotypes were defined using facial landmark distances, identifying five growth patterns: continued-decrease, decrease-to-increase, constant, increase-to-decrease, and continued-increase. We conducted genome-wide association studies (GWAS) for 10 horizontal and 11 vertical phenotypes. The most significant association for horizontal phenotypes was rs610831 (TRIM29; ß = 0.92, p-value = 1.9 × 10-9) and for vertical phenotypes was rs6898746 (ZSWIM6; ß = 0.1103, p-value = 2.5 × 10-8). It is highly correlated with genes already reported for facial growth. This study is the first to classify and characterize facial growth patterns and related genetic polymorphisms.


Subject(s)
Face , Genome-Wide Association Study , Maxillofacial Development , Asian People/genetics , DNA-Binding Proteins/genetics , Humans , Maxillofacial Development/genetics , Phenotype , Republic of Korea , Transcription Factors/genetics
5.
Diagnostics (Basel) ; 12(1)2022 Jan 06.
Article in English | MEDLINE | ID: mdl-35054301

ABSTRACT

Automating screening and diagnosis in the medical field saves time and reduces the chances of misdiagnosis while saving on labor and cost for physicians. With the feasibility and development of deep learning methods, machines are now able to interpret complex features in medical data, which leads to rapid advancements in automation. Such efforts have been made in ophthalmology to analyze retinal images and build frameworks based on analysis for the identification of retinopathy and the assessment of its severity. This paper reviews recent state-of-the-art works utilizing the color fundus image taken from one of the imaging modalities used in ophthalmology. Specifically, the deep learning methods of automated screening and diagnosis for diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma are investigated. In addition, the machine learning techniques applied to the retinal vasculature extraction from the fundus image are covered. The challenges in developing these systems are also discussed.

6.
PLoS One ; 16(12): e0261684, 2021.
Article in English | MEDLINE | ID: mdl-34941933

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown etiology. In several randomized clinical trials, and in the clinical practice, pirfenidone is used to effectively and safely treat IPF. However, sometimes it is difficult to use the dose of pirfenidone used in clinical trials. This study evaluated the effects of low-dose pirfenidone on IPF disease progression and patient survival in the real-world. METHODS: This retrospective, observational study enrolled IPF patients seen at the time of diagnosis at a single center from 2008 to 2018. Longitudinal clinical and laboratory data were prospectively collected. We compared the clinical characteristics, survival, and pulmonary function decline between patients treated and untreated with various dose of pirfenidone. RESULTS: Of 295 IPF patients, 100 (33.9%) received pirfenidone and 195 (66.1%) received no antifibrotic agent. Of the 100 patients who received pirfenidone, 24 (24%), 50 (50%), and 26 (26%), respectively, were given 600, 1200, and 1800 mg pirfenidone daily. The mean survival time was 57.03 ± 3.90 months in the no-antifibrotic drug group and 73.26 ± 7.87 months in the pirfenidone-treated group (p = 0.027). In the unadjusted analysis, the survival of the patients given pirfenidone was significantly better (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.48-0.99, p = 0.04). After adjusting for age, gender, body mass index, and the GAP score [based on gender (G), age (A), and two physiological lung parameters (P)], survival remained better in the patients given pirfenidone (HR = 0.56, 95% CI: 0.37-0.85, p = 0.006). In terms of pulmonary function, the decreases in forced vital capacity (%), forced expiratory volume in 1 s (%) and the diffusing capacity of lung for carbon monoxide (%) were significantly smaller (p = 0.000, p = 0.001, and p = 0.007, respectively) in patients given pirfenidone. CONCLUSIONS: Low-dose pirfenidone provided beneficial effects on survival and pulmonary function decline in the real-world practice.


Subject(s)
Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/mortality , Idiopathic Pulmonary Fibrosis/physiopathology , Pyridones/administration & dosage , Age Factors , Aged , Aged, 80 and over , Body Mass Index , Disease-Free Survival , Female , Humans , Male , Middle Aged , Respiratory Function Tests , Retrospective Studies , Risk Factors , Survival Rate
7.
Front Immunol ; 12: 646316, 2021.
Article in English | MEDLINE | ID: mdl-34691014

ABSTRACT

Atopic dermatitis (AD) is a chronic relapsing pruritic disease encompassing skin inflammation and barrier dysfunction. House dust mites are key allergens that augment the development of atopic dermatitis. We aimed to investigate the pathogenic mechanism of AD due to Der p 38, recently identified by us. The frequency of IgE reactivity to Der p 38 in AD subjects was 52.6% (10/19) in the skin prick test and 57.9% (11/19) in the dot blot assay. In human keratinocyte HaCaT cells, Der p 38 triggered the impairment of filaggrin expression and induced pro-inflammatory cytokines such as IL-6, IL-8 and MCP-1 through TLR4, PI3K, AKT, c-Jun N-terminal kinase (JNK) and NF-κB pathway. Supernatants from Der p 38-treated cells blocked filaggrin expression and neutrophil apoptosis. The anti-apoptotic effect of the Der p 38-released molecules on neutrophils was accomplished by inhibition of the caspase 9/3 pathway, and by increased MCL-1 expression and BCL-2/BAX expression ratio. In C57BL/6 wild type (WT) mice, Der p 38 induced a dose-dependent increase of AD-like skin lesions, with enhanced expressions of total and Der p 38-specific IgE. Der p 38 also diminished the expressions of skin barrier proteins and induced JNK activation. However, the AD-like features following cutaneous Der p 38 exposure were observed to be reduced in the TLR4 knockout (KO) group, as compared to the WT group. Skin infiltration of neutrophils, eosinophils and mast cells was increased in the WT mice, but was not portrayed in the TLR4 KO mice. These findings indicate that Der p 38 is a novel mite allergen that triggers AD by lowering skin barrier proteins and increasing inflammatory cells. Results of this study have thereby paved the way to unveil the pathogenic mechanisms of AD.


Subject(s)
Antigens, Dermatophagoides/immunology , Arthropod Proteins/immunology , Dermatitis, Atopic/immunology , Dermatophagoides farinae/immunology , Keratinocytes/immunology , Skin/immunology , Toll-Like Receptor 4/metabolism , Adult , Animals , Antigens, Dermatophagoides/genetics , Antigens, Dermatophagoides/metabolism , Apoptosis , Apoptosis Regulatory Proteins/metabolism , Arthropod Proteins/genetics , Arthropod Proteins/metabolism , Cytokines/metabolism , Dermatitis, Atopic/genetics , Dermatitis, Atopic/metabolism , Dermatitis, Atopic/pathology , Dermatophagoides farinae/genetics , Dermatophagoides farinae/metabolism , Disease Models, Animal , Eosinophils/immunology , Eosinophils/metabolism , Eosinophils/pathology , Female , Filaggrin Proteins/metabolism , HaCaT Cells , Humans , Immunoglobulin E/blood , Inflammation Mediators/metabolism , Keratinocytes/metabolism , Male , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Neutrophils/immunology , Neutrophils/metabolism , Neutrophils/pathology , Signal Transduction , Skin/metabolism , Skin/pathology , Toll-Like Receptor 4/genetics , Young Adult
8.
J Immunol ; 207(7): 1926-1936, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34470856

ABSTRACT

Innate immune sensing of cytosolic DNA via absent in melanoma 2 (AIM2) is a key mechanism leading to inflammatory responses. As aberrant immune responses by dysregulated AIM2 are associated with autoinflammatory diseases, activation of the AIM2 inflammasome should be tightly controlled. In this study, we discovered that ubiquitination and deubiquitination of AIM2 are critical events that regulate AIM2 inflammasome activation. In resting human macrophage cells, AIM2 is constitutively ubiquitinated and undergoes proteasomal degradation to avoid autoinflammation. Upon DNA stimulation, USP21 binds to AIM2 and deubiquitinates it, thereby increasing its protein stability. In addition to the role of USP21 in regulating AIM2 turnover, we uncovered that USP21-mediated deubiquitination of AIM2 is required for the assembly of the AIM2 inflammasome. Depletion of USP21 does not affect the DNA-binding ability of AIM2 but inhibits the formation of the AIM2-ASC complex. Our findings establish that fine-tuning of AIM2 by the ubiquitin system is important for regulating AIM2 inflammasome activation.


Subject(s)
DNA-Binding Proteins/metabolism , Inflammasomes/metabolism , Inflammation/immunology , Macrophages/immunology , Ubiquitin Thiolesterase/metabolism , Gene Expression Regulation , HEK293 Cells , Humans , Immunity, Innate , Protein Binding , Protein Stability , RNA, Small Interfering/genetics , THP-1 Cells , Ubiquitin Thiolesterase/genetics , Ubiquitination
9.
Proc Natl Acad Sci U S A ; 118(33)2021 08 17.
Article in English | MEDLINE | ID: mdl-34385328

ABSTRACT

Once inside the host cell, DNA viruses must overcome the physical barrier posed by the nuclear envelope to establish a successful infection. The mechanism underlying this process remains unclear. Here, we show that the herpesvirus exploits the immune adaptor stimulator of interferon genes (STING) to facilitate nuclear import of the viral genome. Following the entry of the viral capsid into the cell, STING binds the viral capsid, mediates capsid docking to the nuclear pore complex via physical interaction, and subsequently enables accumulation of the viral genome in the nucleus. Silencing STING in human cytomegalovirus (HCMV)-susceptible cells inhibited nuclear import of the viral genome and reduced the ensuing viral gene expression. Overexpressing STING increased the host cell's susceptibility to HCMV and herpes simplex virus 1 by improving the nuclear delivery of viral DNA at the early stage of infection. These observations suggest that the proviral activity of STING is conserved and exploited by the herpesvirus family. Intriguingly, in monocytes, which act as latent reservoirs of HCMV, STING deficiency negatively regulated the establishment of HCMV latency and reactivation. Our findings identify STING as a proviral host factor regulating latency and reactivation of herpesviruses.


Subject(s)
Cytomegalovirus/physiology , DNA, Viral/metabolism , Genome, Viral/physiology , Membrane Proteins/metabolism , Virus Replication/physiology , Capsid Proteins/genetics , Capsid Proteins/metabolism , Cell Line , DNA, Viral/genetics , Gene Expression Regulation, Viral , Membrane Proteins/genetics , RNA Interference , RNA, Small Interfering , Virus Internalization
10.
Int J Mol Sci ; 22(16)2021 Aug 05.
Article in English | MEDLINE | ID: mdl-34445142

ABSTRACT

It is difficult to treat allergic diseases including asthma completely because its pathogenesis remains unclear. House dust mite (HDM) is a critical allergen and Toll-like receptor (TLR) 4 is a member of the toll-like receptor family, which plays an important role in allergic diseases. The purpose of this study was to characterize a novel allergen, Der f 38 binding to TLR4, and unveil its role as an inducer of allergy. Der f 38 expression was detected in the body and feces of Dermatophagoides farinae (DF). Electron microscopy revealed that it was located in the granule layer, the epithelium layer, and microvilli of the posterior midgut. The skin prick test showed that 60% of allergic subjects were Der f 38-positive. Der f 38 enhanced surface 203c expression in basophils of Der f 38-positive allergic subjects. By analysis of the model structure of Der p 38, the expected epitope sites are exposed on the exterior side. In animal experiments, Der f 38 triggered an infiltration of inflammatory cells. Intranasal (IN) administration of Der f 38 increased neutrophils in the lung. Intraperitoneal (IP) and IN injections of Der f 38 induced both eosinophils and neutrophils. Increased total IgE level and histopathological features were found in BALB/c mice treated with Der f 38 by IP and IN injections. TLR4 knockout (KO) BALB/c mice exhibited less inflammation and IgE level in the sera compared to wild type (WT) mice. Der f 38 directly binds to TLR4 using biolayer interferometry. Der f 38 suppressed the apoptosis of neutrophils and eosinophils by downregulating proteins in the proapoptotic pathway including caspase 9, caspase 3, and BAX and upregulating proteins in the anti-apoptotic pathway including BCL-2 and MCL-1. These findings might shed light on the pathogenic mechanisms of allergy to HDM.


Subject(s)
Allergens/immunology , Antigens, Dermatophagoides/immunology , Arthropod Proteins/immunology , Dermatophagoides farinae/immunology , Hypersensitivity/immunology , Protein Binding/immunology , Toll-Like Receptor 4/immunology , Amino Acid Sequence , Animals , Epitopes/immunology , Female , Humans , Immunoglobulin E/immunology , Mice , Mice, Inbred BALB C , Mice, Knockout , Pyroglyphidae/metabolism , Skin Tests/methods
11.
J Immunol ; 207(7): 1735-1746, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34462314

ABSTRACT

The house dust mite is the most common cause of allergic diseases, and TLR4 acts as an overarching receptor for allergic responses. This study aimed to identify novel allergen binding to TLR4 in house dust mites and unveil its unique role in allergic responses. Der p 38 was purified and characterized by liquid chromatography tandem mass spectrometry-based peptide mapping. Biolayer interferometry and structure modeling unveiled TLR4-binding activity and the structure of recombinant Der p 38. The allergenicity of Der p 38 was confirmed by a skin prick test, and basophil activation and dot blot assays. The skin prick test identified 24 out of 45 allergic subjects (53.3%) as Der p 38+ subjects. Der p 38-augmented CD203c expression was noted in the basophils of Der p 38+ allergic subjects. In animal experiments with wild-type and TLR4 knockout BALB/c mice, Der p 38 administration induced the infiltration of neutrophils as well as eosinophils and exhibited clinical features similar to asthma via TLR4 activation. Persistent Der p 38 administration induced severe neutrophil inflammation. Der p 38 directly suppressed the apoptosis of allergic neutrophils and eosinophils, and enhanced cytokine production in human bronchial epithelial cells, inhibiting neutrophil apoptosis. The mechanisms involved TLR4, LYN, PI3K, AKT, ERK, and NF-κB. These findings may contribute to a deep understanding of Der p 38 as a bridge allergen between eosinophilic and neutrophilic inflammation in the pathogenic mechanisms of allergy.


Subject(s)
Antigens, Dermatophagoides/immunology , Eosinophils/immunology , Hypersensitivity/immunology , Neutrophils/physiology , Respiratory Mucosa/immunology , Animals , Antigens, Dermatophagoides/isolation & purification , Cells, Cultured , Disease Models, Animal , Epitope Mapping , Female , Humans , Immunomodulation , Mice , Mice, Inbred BALB C , Mice, Knockout , Neutrophil Activation , Protein Binding , Signal Transduction , Skin Tests , Toll-Like Receptor 4/metabolism
12.
Article in English | MEDLINE | ID: mdl-33255478

ABSTRACT

Background: Firefighters are vulnerable to irregular sleep patterns and sleep disturbance due to work characteristics such as shift work and frequent dispatch. However, there are few studies investigating intervention targeting sleep for firefighters. This preliminary study aimed to develop and test a sleep intervention, namely FIT-IN (Firefighter's Therapy for Insomnia and Nightmares), which was based on existing evidence-based treatment tailored to firefighters in consideration of their occupational characteristics. Methods: This study implemented a single-group pre-post study design, utilizing an intervention developed based on brief behavior therapy for insomnia with imagery rehearsal therapy components. FIT-IN consisted of a total of three sessions (two face-to-face group sessions and one telephone session). Participants were recruited from Korean fire stations, and a total of 39 firefighters participated. Participants completed a sleep diary for two weeks, as well as the following questionnaires to assess their sleep and psychological factors: insomnia severity index (ISI), disturbing dream and nightmare severity index (DDNSI), Epworth sleepiness scale (ESS), depressive symptom inventory-suicidality subscale (DSI), and Patient Health Questionnaire-9 (PHQ-9). These questionnaires were administered before the first session and at the end of the second session. Results: The FIT-IN program produced improvements in sleep indices. There was a significant increase in sleep efficiency (p < 0.01), and a decrease in sleep onset latency, number of awakenings, and time in bed (p < 0.05), as derived from weekly sleep diaries. In addition, significant decreases were shown for insomnia (p < 0.001) and nightmare severity (p < 0.01). Conclusion: There were significant improvements in sleep and other clinical indices (depression, PTSD scores) when comparing pre-and post-intervention scores. FIT-IN may be a feasible and practical option in alleviating sleep disturbance in this population. Further studies will be needed to ascertain FIT-IN's effectiveness.


Subject(s)
Cognitive Behavioral Therapy , Firefighters , Sleep Initiation and Maintenance Disorders , Dreams , Female , Humans , Male , Sleep , Sleep Initiation and Maintenance Disorders/therapy , Treatment Outcome
13.
Otol Neurotol ; 41(8): 1140-1148, 2020 09.
Article in English | MEDLINE | ID: mdl-33169952

ABSTRACT

OBJECTIVES: This study aimed to demonstrate the application of our automated facial recognition system to measure facial nerve function and compare its effectiveness with other conventional systems and provide a preliminary evaluation of deep learning-facial grading systems. STUDY DESIGN: Retrospective, observational. SETTING: Tertiary referral center, hospital. PATIENTS: Facial photos taken from 128 patients with facial paralysis and two persons with no history of facial palsy were analyzed. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Correlation with Sunnybrook (SB) and House-Brackmann (HB) grading scales. RESULTS: Our results had good reliability and correlation with other grading systems (r = 0.905 and 0.783 for Sunnybrook and HB grading scales, respectively), while being less time-consuming than Sunnybrook grading scale. CONCLUSIONS: Our objective method shows good correlation with both Sunnybrook and HB grading systems. Furthermore, this system could be developed into an application for use with a variety of electronic devices, including smartphones and tablets.


Subject(s)
Facial Paralysis , Facial Recognition , Facial Asymmetry , Facial Paralysis/diagnosis , Humans , Reproducibility of Results , Retrospective Studies
14.
Sensors (Basel) ; 20(9)2020 May 01.
Article in English | MEDLINE | ID: mdl-32369980

ABSTRACT

Facial expressions are one of the important non-verbal ways used to understand human emotions during communication. Thus, acquiring and reproducing facial expressions is helpful in analyzing human emotional states. However, owing to complex and subtle facial muscle movements, facial expression modeling from images with face poses is difficult to achieve. To handle this issue, we present a method for acquiring facial expressions from a non-frontal single photograph using a 3D-aided approach. In addition, we propose a contour-fitting method that improves the modeling accuracy by automatically rearranging 3D contour landmarks corresponding to fixed 2D image landmarks. The acquired facial expression input can be parametrically manipulated to create various facial expressions through a blendshape or expression transfer based on the FACS (Facial Action Coding System). To achieve a realistic facial expression synthesis, we propose an exemplar-texture wrinkle synthesis method that extracts and synthesizes appropriate expression wrinkles according to the target expression. To do so, we constructed a wrinkle table of various facial expressions from 400 people. As one of the applications, we proved that the expression-pose synthesis method is suitable for expression-invariant face recognition through a quantitative evaluation, and showed the effectiveness based on a qualitative evaluation. We expect our system to be a benefit to various fields such as face recognition, HCI, and data augmentation for deep learning.


Subject(s)
Face , Facial Expression , Computer Simulation , Emotions , Facial Muscles , Humans , Imaging, Three-Dimensional , Movement
15.
Proc Natl Acad Sci U S A ; 113(50): 14390-14395, 2016 12 13.
Article in English | MEDLINE | ID: mdl-27911820

ABSTRACT

The innate immune system detects viral nucleic acids and induces type I interferon (IFN) responses. The RNA- and DNA-sensing pathways converge on the protein kinase TANK-binding kinase 1 (TBK1) and the transcription factor IFN-regulatory factor 3 (IRF3). Activation of the IFN signaling pathway is known to trigger the redistribution of key signaling molecules to punctate perinuclear structures, but the mediators of this spatiotemporal regulation have yet to be defined. Here we identify butyrophilin 3A1 (BTN3A1) as a positive regulator of nucleic acid-mediated type I IFN signaling. Depletion of BTN3A1 inhibits the cytoplasmic nucleic acid- or virus-triggered activation of IFN-ß production. In the resting state, BTN3A1 is constitutively associated with TBK1. Stimulation with nucleic acids induces the redistribution of the BTN3A1-TBK1 complex to the perinuclear region, where BTN3A1 mediates the interaction between TBK1 and IRF3, leading to the phosphorylation of IRF3. Furthermore, we show that microtubule-associated protein 4 (MAP4) controls the dynein-dependent transport of BTN3A1 in response to nucleic acid stimulation, thereby identifying MAP4 as an upstream regulator of BTN3A1. Thus, the depletion of either MAP4 or BTN3A1 impairs cytosolic DNA- or RNA-mediated type I IFN responses. Our findings demonstrate a critical role for MAP4 and BTN3A1 in the spatiotemporal regulation of TBK1, a central player in the intracellular nucleic acid-sensing pathways involved in antiviral signaling.


Subject(s)
Antigens, CD/metabolism , Butyrophilins/metabolism , Dyneins/metabolism , Interferon Regulatory Factor-3/metabolism , Microtubule-Associated Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Active Transport, Cell Nucleus , Antigens, CD/genetics , Butyrophilins/antagonists & inhibitors , Butyrophilins/genetics , Cell Line , DNA, Viral/immunology , Gene Knockdown Techniques , HEK293 Cells , HeLa Cells , Humans , Immunity, Innate , Interferon Type I/biosynthesis , Microtubules/metabolism , Models, Biological , Phosphorylation , RNA, Small Interfering/genetics , RNA, Viral/immunology , Signal Transduction
16.
Biol Pharm Bull ; 38(7): 1081-6, 2015.
Article in English | MEDLINE | ID: mdl-26133719

ABSTRACT

To identify bioactive natural products possessing anti-inflammatory activity, the potential of fulgidic acid from the rhizomes of Cyperus rotundus and the underlying mechanisms involved in its anti-inflammatory activity were evaluated in this study. Fulgidic acid reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Consistent with these findings, fulgidic acid suppressed the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein level, as well as iNOS, COX-2, TNF-α, and IL-6 at mRNA levels. Fulgidic acid suppressed the LPS-induced transcriptional activity of activator protein-1 (AP-1) as well as the phosphorylation of c-Fos and c-Jun. On the other hand, fulgidic acid did not show any effect on LPS-induced nuclear factor κB (NF-κB) activity. Taken together, these results suggest that the anti-inflammatory effect of fulgidic acid is associated with the suppression of iNOS, COX-2, TNF-α, and IL-6 expression through down-regulating AP-1 activation in LPS-induced RAW264.7 macrophages.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Cyperus , Linoleic Acids/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Cell Line , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Dinoprostone/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Linoleic Acids/isolation & purification , Lipopolysaccharides , Mice , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Rhizome , Transcription Factor AP-1/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
17.
Cell Host Microbe ; 17(6): 838-51, 2015 Jun 10.
Article in English | MEDLINE | ID: mdl-26067606

ABSTRACT

Temporal profiles of miRNA activity during productive virus infection can provide fundamental insights into host-virus interactions. Most reported miRNA targetome analyses in the context of virus infection have been performed in latently infected cells and lack reliable models for quantifying the suppression efficacy at specific miRNA target sites. Here, we identified highly competent temporal miRNA targetomes during lytic HCMV infection by using AGO-CLIP-seq together with a bioinformatic method that quantifies miRNA functionality at a specific target site, called ACE-scoring. The repression efficiency at target sites correlates with the magnitude of the ACE-score, and temporal HCMV-encoded miRNA targetomes identified by ACE-scoring were significantly enriched in functional categories involved in pathways central for HCMV biology. Furthermore, comparative analysis between human and viral miRNA targetomes supports the existence of intimate cooperation and co-targeting between them. Our holistic survey provides a valuable resource for understanding host-virus interactions during lytic HCMV infection.


Subject(s)
Cytomegalovirus Infections/virology , Cytomegalovirus/genetics , Gene Expression Regulation, Viral , Host-Pathogen Interactions , MicroRNAs , Cytomegalovirus/pathogenicity , Gene Expression Profiling/methods , HeLa Cells/virology , Humans , Interferons/metabolism , Janus Kinases/metabolism , MicroRNAs/genetics , Reproducibility of Results , STAT Transcription Factors/metabolism , Sequence Analysis, RNA/methods , Signal Transduction/genetics
18.
Cell Host Microbe ; 13(6): 678-90, 2013 Jun 12.
Article in English | MEDLINE | ID: mdl-23768492

ABSTRACT

Virulence of human cytomegalovirus (HCMV) clinical isolates correlates with carriage of a 15 kb segment in the UL/b' region of the viral genome, which is absent from attenuated strains. The mechanisms by which this segment contributes to HCMV virulence remain obscure. We observed that intergenic RNA sequences within the 15 kb segment function as a microRNA (miRNA) decay element (miRDE) and direct the selective, sequence-specific turnover of mature miR-17 and miR-20a encoded within the host miR-17-92 cluster. Unlike canonical miRNA-mRNA interactions, the miRNA-miRDE interactions did not repress miRDE expression. miRNA binding site mutations retargeted miRDE to other miR-17-92 cluster miRNAs, which are otherwise resistant to miRDE-mediated decay. miRDE function was required to accelerate virus production in the context of lytic HCMV infection. These results indicate a role for viral noncoding RNA in regulating cellular miRNAs during HCMV pathogenesis and suggest that noncoding RNAs may play a role in mature miRNA turnover.


Subject(s)
Cytomegalovirus/physiology , Host-Pathogen Interactions , MicroRNAs/metabolism , RNA Stability , RNA, Viral/metabolism , Virus Replication , Binding Sites , Cell Line , DNA Mutational Analysis , DNA, Intergenic , Gene Expression Profiling , Humans
19.
J Food Prot ; 76(1): 133-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23317869

ABSTRACT

There has been an increasing interest in the use of natural plant materials as alternative food preservatives. We examined the antimicrobial effects of natural plant materials used as additives against foodborne pathogens in laboratory media and Sulgidduk, oriental-style rice cakes. Cinnamon, mugwort, and garlic powder solutions (3%) were tested for their antimicrobial activities against pathogens in laboratory media. Sulgidduk prepared with different amounts of cinnamon powder (1, 3, and 6%) was inoculated with a Staphylococcus aureus or Bacillus cereus cocktail. The samples were air or vacuum packaged and stored at 22 ± 1°C for 72 h, and microbial growth was determined. Cinnamon powder showed more inhibitory properties against pathogens such as Salmonella enterica serovar Typhimurium, Escherichia coli O157:H7, Listeria monocytogenes, S. aureus, and B. cereus than did mugwort or garlic powder. The populations of S. aureus and B. cereus in Sulgidduk containing cinnamon powder were significantly lower than in the control during storage time. Different packaging methods did not result in a significant difference in pathogen growth. In a sensory evaluation, Sulgidduk containing 1 and 3% cinnamon powder did not significantly differ from the control sample in any of the attributes tested other than flavor. These results indicate that natural plant materials such as cinnamon powder could be used as food additives to improve the microbiological stability of rice cakes.


Subject(s)
Cinnamomum zeylanicum , Food Preservation/methods , Food Preservatives/pharmacology , Plant Preparations/pharmacology , Artemisia , Bacillus cereus/drug effects , Bacillus cereus/growth & development , Colony Count, Microbial , Consumer Product Safety , Dose-Response Relationship, Drug , Escherichia coli O157/drug effects , Escherichia coli O157/growth & development , Food Contamination/analysis , Food Contamination/prevention & control , Food Microbiology , Garlic , Humans , Listeria monocytogenes/drug effects , Listeria monocytogenes/growth & development , Oryza/microbiology , Powders , Salmonella typhimurium/drug effects , Salmonella typhimurium/growth & development , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Taste
SELECTION OF CITATIONS
SEARCH DETAIL
...