Association of Cough Severity with Asthma Control and Quality of Life in Patients with Severe Asthma.

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.

Anticancer Activity of Astaxanthin-Incorporated Chitosan Nanoparticles.

Astaxanthin (AST)-encapsulated nanoparticles were fabricated using glycol chitosan (Chito) through electrostatic interaction (abbreviated as ChitoAST) to solve the aqueous solubility of astaxanthin and improve its biological activity. AST was dissolved in organic solvents and then mixed with chitosan solution, followed by a dialysis procedure. All formulations of ChitoAST nanoparticles showed small diameters (less than 400 nm) with monomodal distributions. Analysis with Fourier transform infrared (FT-IR) spectroscopy confirmed the specific peaks of AST and Chito. Furthermore, ChitoAST nanoparticles were formed through electrostatic interactions between Chito and AST. In addition, ChitoAST nanoparticles showed superior antioxidant activity, as good as AST itself; the half maximal radical scavenging concentrations (RC50) of AST and ChitoAST nanoparticles were 11.8 and 29.3 µg/mL, respectively. In vitro, AST and ChitoAST nanoparticles at 10 and 20 µg/mL properly inhibited the production of intracellular reactive oxygen species (ROSs), nitric oxide (NO), and inducible nitric oxide synthase (iNOS). ChitoAST nanoparticles had no significant cytotoxicity against RAW264.7 cells or B16F10 melanoma cells, whereas AST and ChitoAST nanoparticles inhibited the growth of cancer cells. Furthermore, AST itself and ChitoAST nanoparticles (20 µg/mL) efficiently inhibited the migration of cancer cells in a wound healing assay. An in vivo study using mice and a pulmonary metastasis model showed that ChitoAST nanoparticles were efficiently delivered to a lung with B16F10 cell metastasis; i.e., fluorescence intensity in the lung was significantly higher than in other organs. We suggest that ChitoAST nanoparticles are promising candidates for antioxidative and anticancer therapies of B16F10 cells.

A Comparative Study of Endoscopic versus Percutaneous Epidural Neuroplasty in Lower Back Pain: Outcomes at Six-Month Follow Up.

Background and Objectives: Endoscopic epidural neuroplasty (EEN) facilitates adhesiolysis through direct epiduroscopic visualization, offering more precise neural decompression than that exhibited by percutaneous epidural neuroplasty (PEN). We aimed to compare the effects of EEN and PEN for 6 months after treatment with lower back and radicular pain in patients. Methods: This retrospective study compared the visual analog scale (VAS) and Oswestry disability index (ODI) scores in patients with low back and radicular pain who underwent EEN or PEN with a steering catheter. The medical records of 107 patients were analyzed, with 73 and 34 undergoing EEN and PEN, respectively. Results: The VAS and ODI scores decreased at all time points after EEN and PEN. VAS and ODI scores decreased more in the EEN group than those in the PEN group at 1 day and 1- and 6-months post-procedure, indicating superior pain relief for both lower back and radicular pain through EEN. Conclusions: EEN is a superior treatment of pain control than PEN in lower back and radicular pain patients.

Role of IL-22 in acute asthma mouse model.

Introduction: Allergic asthma is often associated with eosinophilic inflammation, which is related to the T-helper cell type 2 (Th2) cytokines and responsive to corticosteroids. However, there are also phenotypes of non-Th2-mediated asthma, which have poor responsivity to corticosteroids. The leading phenotype of non-Th2-mediated asthma is neutrophilic asthma, which is considered difficult to treat. Recently, IL-22 has been found to be involved in neutrophilic inflammation in asthma. However, studies on the role of IL-22 in asthma are still controversial as IL-22 has both pro-inflammatory and anti-inflammatory roles in asthma. This study examined whether the IL-22 level increased in acute neutrophilic asthma in the mouse model. Herein, we aimed to demonstrate increased IL-22 levels in neutrophilic asthma and elucidate the pathways leading to elevated neutrophil counts.Methods: Six-week old female BALB/c mice were sensitized and challenged with PBS, ovalbumin (OVA) or OVA + lipopolysaccharide (LPS). The mice were then assigned to one of the following five groups: (1) control (PBS/ PBS), (2) OVA/PBS, (3) OVA/OVA, (4) OVA+LPS/PBS, (5) OVA+LPS/OVA+LPS.Results: The levels of Th2 cytokines, IL-17, and IL-22 were assessed, with investigation of the neutrophil chemokines. This study showed that in the acute neutrophilic asthma, the levels of IL-17 and IL-22 were significantly higher than those in the OVA/OVA group, which represents acute eosinophilic asthma. Moreover, the level of CCL20 increased in the neutrophilic asthma group.Conclusion: Thus, this study suggests that in the acute neutrophilic asthma mouse model, IL-17 and IL-22 may increase with CCL20, resulting in neutrophilic inflammation.

Platycodin D attenuates airway inflammation via suppression Th2 transcription factor in a murine model of acute asthma.

Introduction: Bronchial asthma is a common chronic inflammatory condition of the airway tissue. Platycodin D (PLD) has antiinflammatory effects in a mouse model of allergic asthma. In this work, the anti-asthma potential of PLD was studied by investigation of its effect to suppress airway inflammation and mucin production, a murine model of asthma and the possible mechanisms.Methods: Mice were randomly assigned to five experimental groups: control, ovalbumin (OVA), OVA+ICS (intranasal fluticasone), OVA+PLD and OVA+PLD/ICS. Airway histological studies were evaluated by the H&E staining; IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid were evaluated by ELISA; GATA3 and IRF4 mRNA of airway were measured by RT-PCR and their protein level were measured by Western blotting.Results: Our study showed that PLD suppressed eosinophilic inflammation and mucin production in bronchial mucosa. Moreover, PLD inhibited production of Th2 cytokines such as IL-4, IL-5, and IL-13. Protein production of GATA3 and IRF4, were also decreased in PLD treated OVA asthma model. Taken together, our results provided evidence that PLD inhibits the airway inflammation via suppression of Th2 transcription factor production.Conclusion: These findings suggest that PLD may effectively ameliorate the progression of asthma. These results suggest that PLD could be used as a therapy for allergic asthma.

Glucagon-like peptide 1 receptor (GLP-1R) agonist relieved asthmatic airway inflammation via suppression of NLRP3 inflammasome activation in obese asthma mice model.

BACKGROUND: Obesity is a correctable factor for uncontrolled bronchial asthma. However, the effects of glucagon-like peptide-1 receptor (GLP-1R) agonist, a recently approved antiobestic drug, on airway hyperresponsiveness (AHR) and immune responses are not known. METHODS: Mice were fed with high-fat diet (HFD, 60% fat) for 8 weeks to induce obesity. Ovalbumin (OVA) sensitization and challenges were performed for 7 weeks. The mice were injected intraperitoneally with GLP-1R agonist 5 times a week for 4 weeks after OVA sensitization. After AHR measurement, expression of Th2, Th17 cytokines, and interleukin (IL)-33 were measured in BALF and lung tissues. Moreover, IL-1ß and activity level of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) were analyzed to investigate the mechanism of GLP-1R agonist on asthmatic airway inflammation. RESULTS: HFD induced significant weight gain, OVA sensitization and challenge in obese mice made eosinophilic airway inflammation, and increased AHR. Treatment with GLP-1R agonist-induced weight loss suppressed eosinophilic airway inflammation and decreased AHR. Expression of IL-4, 5, and 33 was increased in BALF of obese asthma mice followed by a decrease in response to GLP-1R agonist treatment. Moreover, lung tissue H&E stain revealed that peribronchial inflammation induced by obesity and OVA was effectively suppressed by GLP-1R agonist. Expressions of NLRP3, activated caspase-1, and IL-1ß were increased in lung tissues of obese asthma mice and demonstrated a decrease in response to GLP-1R agonist treatment. CONCLUSIONS: GLP-1R agonist effectively induced weight loss, suppressed eosinophilic bronchial airway inflammation, and AHR in obese asthma mice. These effects were mediated by suppression of NLRP3 inflammasome activity and IL-1ß. GLP-1R agonist is proposed as a novel anti-asthmatic agent targeting the obese asthmatics.

Cyclo-VEGI inhibits bronchial artery remodeling in a murine model of chronic asthma.

Purpose/Aim: In the context of asthma, airway bronchial remodeling and angiogenesis in the bronchial mucosa are well established. Cyclopeptidic-vascular endothelial growth inhibitor (cyclo-VEGI) is an inhibitor of the vascular endothelial growth factor (VEGF) receptor that increases the proliferation of endothelial cells and the formation of new vessels. However, changes in the bronchial arteries of patients with asthma have not been clearly elucidated. We investigated whether structural changes occurred in bronchial arteries, as well as the effects of cyclo-VEGI in a mouse model of chronic asthma (in vivo) and human fibroblasts (in vitro). Materials and Methods: A validated mouse model of allergic airway inflammation with ovalbumin (OVA) as the causative allergen was used for the study. Mice were treated with cyclo-VEGI or fluticasone during OVA challenge. In vitro experiments were conducted to determine whether fibroblasts proliferated following elastin exposure and the effects of cyclo-VEGI on them. Results: OVA sensitization and challenge led to greater perivascular smooth muscle area, more elastic fibers, and elevated expression of vascular cell adhesion molecule (VCAM)-1 antigen. These phenomena indicated changes to bronchial arteries. Cyclo-VEGI and fluticasone treatment both inhibited airway hyper-responsiveness and inflammation. Cyclo-VEGI-treated mice exhibited decreased perivascular smooth muscle area, elastin fibers, and VCAM-1 expression. Fluticasone-treated mice exhibited reductions in perivascular smooth muscle but not in perivascular elastin or VCAM-1 expression. In vitro, fibroblast proliferation was enhanced by elastin treatment, which was inhibited by cyclo-VEGI treatment. Eotaxin expression was elevated in elastin-treated fibroblasts and decreased with cyclo-VEGI treatment. Conclusions: Vascular remodeling occurred in our mouse model of chronic asthma. Cyclo-VEGI could reduce airway inflammation and hyper-responsiveness by inhibiting VCAM-1 expression and elastin deposition around the bronchial arteries.

Effect of Cognitive Training in Fully Immersive Virtual Reality on Visuospatial Function and Frontal-Occipital Functional Connectivity in Predementia: Randomized Controlled Trial.

BACKGROUND: Cognitive training can potentially prevent cognitive decline. However, the results of recent studies using semi-immersive virtual reality (VR)-assisted cognitive training are inconsistent. OBJECTIVE: We aimed to examine the hypothesis that cognitive training using fully immersive VR, which may facilitate visuospatial processes, could improve visuospatial functioning, comprehensive neuropsychological functioning, psychiatric symptoms, and functional connectivity in the visual brain network in predementia. METHODS: Participants over 60 years old with subjective cognitive decline or mild cognitive impairment from a memory clinic were randomly allocated to the VR (n=23) or the control (n=18) group. The VR group participants received multidomain and neuropsychologist-assisted cognitive training in a fully immersive VR environment twice a week for 1 month. The control group participants did not undergo any additional intervention except for their usual therapy such as pharmacotherapy. Participants of both groups were evaluated for cognitive function using face-to-face comprehensive neuropsychological tests, including the Rey-Osterrieth Complex Figure Test (RCFT) copy task; for psychiatric symptoms such as depression, apathy, affect, and quality of life; as well as resting-state functional magnetic resonance imaging (rsfMRI) at baseline and after training. Repeated-measures analysis of variance was used to compare the effect of cognitive training between groups. Seed-to-voxel-based analyses were used to identify the cognitive improvement-related functional connectivity in the visual network of the brain. RESULTS: After VR cognitive training, significant improvement was found in the total score (F1,39=14.69, P=.001) and basic components score of the RCFT copy task (F1,39=9.27, P=.005) compared with those of the control group. The VR group also showed improvements, albeit not significant, in naming ability (F1,39=3.55, P=.07), verbal memory delayed recall (F1,39=3.03, P=.09), and phonemic fluency (F1,39=3.08, P=.09). Improvements in psychiatric symptoms such as apathy (F1,39=7.02, P=.01), affect (F1,39=14.40, P=.001 for positive affect; F1,39=4.23, P=.047 for negative affect), and quality of life (F1,39=4.49, P=.04) were found in the VR group compared to the control group. Improvement in the RCFT copy task was associated with a frontal-occipital functional connectivity increase revealed by rsfMRI in the VR group compared to the control group. CONCLUSIONS: Fully immersive VR cognitive training had positive effects on the visuospatial function, apathy, affect, quality of life, and increased frontal-occipital functional connectivity in older people in a predementia state. Future trials using VR cognitive training with larger sample sizes and more sophisticated designs over a longer duration may reveal greater improvements in cognition, psychiatric symptoms, and brain functional connectivity. TRIAL REGISTRATION: Clinical Research Information Service KCT0005243; https://tinyurl.com/2a4kfasa.

Intergenic recombination in feline calicivirus associated with a hemorrhagic-like disease in the Republic of Korea.

Feline calicivirus (FCV) is a common cause of upper respiratory tract disease in cats. In this study, the complete genome sequence of FCV 14Q315, which was detected from a dead domestic cat with a hemorrhagic-like disease, was analyzed to identify the genetic characteristics. The FCV 14Q315 genome was 7,684 bp. Phylogenetic analyses based on the ORF1, ORF2, and ORF3 sequences indicated that FCV 14Q315 is more closely related to FCV 15D022 than to other FCV strains. ORF1 of FCV 14Q315 shared high sequence similarity with ORF1 of FCVs 15D022 and UTCVM-H1. We further evaluated genetic recombination in ORF1 of FCV 14Q315 and detected intergenic recombination between p30 and the ORF1/ORF2 junction with high significance. Particularly, the non-recombination region in ORF1 of FCV 14Q315 showed high sequence similarity with FCVs GX2019, CH-JL2, and 15D022. The recombination region in ORF1 of FCV 14Q315 showed the highest similarity with FCV UTCVM-H1, which is associated with a hemorrhagic-like disease. The results suggest that the UTCVM-H1-like FCV was introduced into the Republic of Korea and presumably recombined with Korean FCVs by occasional mixed infections. In addition, the Korean FCV strains were located in several phylogenetic clusters with marked genetic diversity in the ORF2 region. These results imply that Korean FCVs possess high genetic diversity owing to mutations and recombination. Furthermore, it is possible that certain FCVs caused cyclical infections in the Korean cat population based on a phylogenetic analysis of FCVs isolated at different time points. Keywords: calicivirus; virulent systemic feline calicivirus; recombination; hemorrhagic-like disease.

Metabolic profiling and antioxidant activity during flower development in Agastache rugosa.

Our previous study showed that flowers of Agastache rugosa had higher phenolic levels and higher antibacterial and antioxidant capacity compared to those of the leaves and stems. The aim of this study was to provide information on the variation in primary and secondary metabolites during flower development in A. rugosa by using high performance liquid chromatography (HPLC) and assays of total anthocyanin (TAC), flavonoid (TFC), and phenolic content (TPC), as well as gas chromatography time-of-flight mass spectrometry (GC-TOFMS) analysis. Assays of TPC, TAC, and TFC showed that the floral bud (stage I) contained higher TPC than did the partially open flower (stage II) and fully open flower (stage III). However, the TFC was the highest at stage II, and the highest TAC was observed at stage III. Furthermore, HPLC analysis revealed that the level of total phenylpropanoids, including rosmarinic acid, tilianin, acacetin, 4-hydroxybenzoic acid, caffeic acid, chlorogenic acid, trans-cinnamic acid, rutin, (-)-epicatechin, quercetin, and kaempferol, was higher in stages I and II, but the concentrations of rutin and rosmarinic acid were highest in stage III. A total of 43 compounds, including amino acids, organic acids, phenolic compounds, sugars, photorespiration-related compounds, and intermediates of the tricarboxylic acid cycle, were identified through GC-TOFMS analysis. Of these compounds, most amino acids decreased during flower development. In contrast, the increase in concentrations of glucose and sucrose were observed from stages I to III. In this study, health-beneficial compounds were identified and quantified in flowers of A. rugosa. Accordingly, our results suggests that A. rugosa flowers can potentially be used as biomaterials for pharmaceuticals, cosmetics, food, and related industries. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1007/s12298-021-00945-z).

Honokiol ameliorates angiotensin II-induced hypertension and endothelial dysfunction by inhibiting HDAC6-mediated cystathionine γ-lyase degradation.

Hypertension and endothelial dysfunction are associated with various cardiovascular diseases. Hydrogen sulphide (H2 S) produced by cystathionine γ-lyase (CSE) promotes vascular relaxation and lowers hypertension. Honokiol (HNK), a natural compound in the Magnolia plant, has been shown to retain multifunctional properties such as anti-oxidative and anti-inflammatory activities. However, a potential role of HNK in regulating CSE and hypertension remains largely unknown. Here, we aimed to demonstrate that HNK co-treatment attenuated the vasoconstriction, hypertension and H2 S reduction caused by angiotensin II (AngII), a well-established inducer of hypertension. We previously found that histone deacetylase 6 (HDAC6) mediates AngII-induced deacetylation of CSE, which facilitates its ubiquitination and proteasomal degradation. Our current results indicated that HNK increased endothelial CSE protein levels by enhancing its stability in a sirtuin-3-independent manner. Notably, HNK could increase CSE acetylation levels by inhibiting HDAC6 catalytic activity, thereby blocking the AngII-induced degradative ubiquitination of CSE. CSE acetylation and ubiquitination occurred mainly on the lysine 73 (K73) residue. Conversely, its mutant (K73R) was resistant to both acetylation and ubiquitination, exhibiting higher protein stability than that of wild-type CSE. Collectively, our findings suggested that HNK treatment protects CSE against HDAC6-mediated degradation and may constitute an alternative for preventing endothelial dysfunction and hypertensive disorders.

Clinical pathway for enhanced recovery after surgery for gastric cancer: A prospective single-center phase II clinical trial for safety and efficacy.

BACKGROUND: We aimed to evaluate the safety and efficacy of a clinical pathway (CP) for enhanced recovery after surgery (ERAS) in gastric cancer patients, including early oral feeding and discharge on postoperative day 4. METHODS: We performed a prospective, single-center, phase II clinical trial. Based on proposed indications for an ERAS CP in our retrospective study, we enrolled 133 patients younger than 65 years who were undergoing minimally invasive subtotal gastrectomy. The primary endpoint was the ERAS CP completion rate. Secondary endpoints included complication, mortality, hospital stay, and readmission. RESULTS: Among 133 patients, six patients were dropped out from this study. The ERAS CP completion rate (77.2%, 98 of 127) was comparable to the historical control group that completed a conventional CP (85.4%, P = .085). The postoperative complication incidence (13.4%, 15 of 127) was also similar to that of the conventional CP group (9.5%, P = .174). We identified reduced hospital stays (4.7 ± 1.3 vs 7.2±2.3 days; P < .001) and lower hospital costs ($7771 vs 8539; P < .001) in the ERAS CP group compared with the conventional CP group. CONCLUSIONS: An ERAS CP can be safely and effectively adopted for patients with gastric cancer without increasing the complication rate and could shorten hospital stays. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01642953).

Effect of nintedanib on airway inflammation in a mouse model of acute asthma.

Objective: New treatments are needed for cases of asthma that are refractory to traditional therapies. In this study, we examined the effect of oral nintedanib, an intracellular inhibitor of tyrosine kinases, on airway hyper-responsiveness (AHR) and airway smooth muscle cells, using a mouse model of experimental asthma. Methods: Asthma was experimentally induced in mice via subcutaneous injection of ovalbumin (OVA). A group of saline-injected mice served as a control group. The OVA mice were then divided into four treatment groups according to the dose of nintedanib. AHR was examined via exposure to vaporized methacholine. Airway inflammation was assessed via bronchoalveolar lavage fluid (BALF) cell counts and Th2 cytokine concentrations. Results: Baseline levels of AHR and airway inflammation were higher in OVA mice than in the control group. Treatment with nintedanib lowered AHR, BALF cell counts and BALF cytokine levels in a dose-dependent fashion. The effect of nintedanib was comparable to that of dexamethasone. In particular, treatment with nintedanib lowered the expression of transforming growth factor-ß1 and inhibited the expression and phosphorylation of platelet-derived growth factor receptor-ß, vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2, fibroblast growth factor receptor 2 (FGFR2), FGFR3, and extracellular signal-regulated kinase. Conclusions: Nintedanib lowered AHR and the expression of factors associated with airway inflammation and remodeling in a mouse model of experimental asthma. Our results suggest that nintedanib may be useful in the treatment of asthma.

Evaluation of Human MSCs Treatment Frequency on Airway Inflammation in a Mouse Model of Acute Asthma.

BACKGROUND: Studies in experimental models of allergic asthma have shown that mesenchymal stem cells (MSCs) have therapeutic potential for T-helper 2 (TH2) cell-mediated inflammation. However, the mechanisms underlying these therapeutic effects are not fully understood and their safety has not been confirmed. METHODS: Using a mouse model of experimental allergic asthma, we investigated the efficacy of human adipose-derived mesenchymal stem cells (hADSCs) or human bone marrow-derived mesenchymal stem cells (hBMSCs) according to treatment frequency and timing. RESULTS: Ovalbumin (OVA)-sensitized and -challenged mice exhibited airway hyperresponsiveness (AHR), airway inflammation, and significant increases in TH2 cytokine levels. Both double and single human mesenchymal stem cell (hMSC) treatments significantly decreased AHR and bronchoalveolar lavage fluid counts. In addition, single treatment with hMSCs showed significant attenuation of allergic airway inflammation. However, double treatment with hMSCs during OVA -sensitization and -challenge further increased inflammatory cell infiltration, and TH2 cytokine levels. CONCLUSION: The results of treatment with hADSCs or hBMSCs suppresses AHR and airway inflammation. However, double hMSC treatment significantly induces eosinophilic airway inflammation and lung histological changes. Therefore, double hMSC treatment is ineffective against asthma and single injection frequency appears to be more important for the treatment of asthma. These results suggest that hMSC therapy can be used for treatment of asthma patients but that it should be used carefully.

Complete genome analysis of a SARS-like bat coronavirus identified in the Republic of Korea.

Bats have been widely known as natural reservoir hosts of zoonotic diseases, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) caused by coronaviruses (CoVs). In the present study, we investigated the whole genomic sequence of a SARS-like bat CoV (16BO133) and found it to be 29,075 nt in length with a 40.9% G+C content. Phylogenetic analysis using amino acid sequences of the ORF 1ab and the spike gene showed that the bat coronavirus strain 16BO133 was grouped with the Beta-CoV lineage B and was closely related to the JTMC15 strain isolated from Rhinolophus ferrumequinum in China. However, 16BO133 was distinctly located in the phylogenetic topology of the human SARS CoV strain (Tor2). Interestingly, 16BO133 showed complete elimination of ORF8 regions induced by a frame shift of the stop codon in ORF7b. The lowest amino acid identity of 16BO133 was identified at the spike region among various ORFs. The spike region of 16BO133 showed 84.7% and 75.2% amino acid identity with Rf1 (SARS-like bat CoV) and Tor2 (human SARS CoV), respectively. In addition, the S gene of 16BO133 was found to contain the amino acid substitution of two critical residues (N479S and T487 V) associated with human infection. In conclusion, we firstly carried out whole genome characterization of the SARS-like bat coronavirus discovered in the Republic of Korea; however, it presumably has no human infectivity. However, continuous surveillance and genomic characterization of coronaviruses from bats are necessary due to potential risks of human infection induced by genetic mutation.

Pravastatin alleviates allergic airway inflammation in obesity-related asthma mouse model.

Background: Obesity is one of the factors associated with severe, uncontrolled asthma. The effect of pravastatin on asthmatic airway inflammation in obesity has not been evaluated. Methods: C57BL/6 mice were fed a high-fat diet (HFD) to induce obesity with or without ovalbumin (OVA) sensitization and challenge. Pravastatin was administered intraperitoneally during the OVA treatment. Airway inflammation and airway hyper-responsiveness (AHR) were analyzed and lung tissues were examined. The changes in mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt signaling pathways were measured in the lung tissues. Results: HFD with OVA sensitization and challenge exacerbated eosinophilic and neutrophilic airway inflammation and increased AHR compared to lean asthma mice. The levels of cytokines examined in bronchoalveolar lavage fluid (BALF) revealed that the expressions of IL-4, 5, and 17 were elevated in the obese asthmatic group and decreased after pravastatin treatment, indicating that both the Th2 and Th17 pathways were stimulated by HFD-induced obesity and OVA challenge and suppressed by pravastatin treatment. Moreover, the serum leptin and adiponectin ratio was elevated only in obese asthmatic mice and decreased with pravastatin administration. Pravastatin successfully alleviated the airway inflammation of lung tissues and AHR in both obese and lean asthmatic mice, however, treatment with pravastatin had no effects on BALF cell counts and cytokines in lean asthma mice. In lung tissues, the phosphorylation of p38 MAPK was significantly decreased in lean as well as obese asthmatic mice. Conclusions: Pravastatin treatment in obese asthmatic mice suppressed allergic airway infiltration and AHR by inhibition of Th2 and Th17-associated signaling pathways, decreasing the leptin expression and downstream p38 MAPK signaling pathways. The effect on lean asthmatic mice was different, independent of airway cell counts and cytokines.

Comparison of Pentax Airway Scope and Macintosh laryngoscope for orotracheal intubation in children: A randomised non-inferiority trial.

BACKGROUND: Pentax Airway Scope (AWS) is a recently developed videolaryngoscope for use in both normal and difficult airways, yet its use in paediatric patients has not been established. The purpose of this study was to evaluate the efficacy of the Pentax AWS regarding intubation time, laryngeal view and ease of intubation in paediatric patients with normal airway, compared to Macintosh laryngoscope. METHOD: A total of 136 paediatric patients aged 1-10 with American Society of Anaesthesiologists physical status I or II undergoing general anaesthesia were randomly allocated into two groups: Macintosh laryngoscope (n = 68) and Pentax Airway Scope (n = 68). Primary outcome was intubation time. Cormack-Lehane laryngeal view grade, application of optimal laryngeal external manipulation, intubation difficulty scale, intubation failure rate and adverse events were also measured. RESULT: No significant difference was observed between the two groups regarding intubation time (P = 0.713). As for the laryngeal view grade, the Pentax group resulted in lower graded cases compared to the Macintosh group (P = 0.000). No optimal laryngeal external manipulation application was required in the Pentax group. Intubation difficulty scale resulted in lower values for Pentax group (P = 0.001). Failure rate was not different between the two groups (P = 0.619). There were significantly more teeth injury cases in the Pentax group than Macintosh group (P = 0.042). CONCLUSION: Pentax Airway Scope provided similar intubation time and success rate, while improving laryngeal view, compared to Macintosh laryngoscopy in children with normal airway. When using Pentax AWS in children, however, the risk of teeth injury may increase.

Comparative analysis of glucosinolate production in hairy roots of green and red kale (Brassica oleracea var. acephala).

Glucosinolates (GSLs) are sulfur- and nitrogen-containing secondary metabolites that function in plant defense and provide benefits to human health. In this study, using Agrobacterium rhizogenes R1000, green and red kale hairy roots were established. The expression levels of GSLs biosynthesis genes and their accumulation in both kale hairy roots were analyzed by quantitative real-time PCR and HPLC. The results showed that the expression of most indolic GSLs biosynthesis genes was higher in the hairy roots of green kale than in that of red kale. In contrast, the expression of BoCYP83A1 and BoSUR1 encoding key enzymes aromatic GSL biosynthesis was significantly higher in red kale hairy root. The HPLC analysis identified six GSLs. The levels of 4-methoxyglucobrassicin, glucobrassicin, and 4-hydroxyglucobrassicin were 6.21, 5.98, and 2 times higher, respectively, in green kale than in red kale, whereas the levels of neoglucobrassicin and gluconasturtiin were 16.2 and 3.48 times higher, respectively, in red kale than in green kale. Our study provides insights into the underlying mechanisms of GSLs biosynthesis in kale hairy roots and can be potentially used as "biological factories" for producing bioactive substances such as GSLs.

The leukotriene receptor antagonist pranlukast attenuates airway remodeling by suppressing TGF-ß signaling.

BACKGROUND/OBJECTIVE: Asthma is a chronic airway disease characterized by airway eosinophilic inflammation and remodeling, which are associated with a loss in lung function. Although both contribute significantly to asthma pathogenesis, mechanistic studies and drug discovery have focused on inflammatory targets. In this study, we investigated the effect of the leukotriene receptor antagonist pranlukast on allergic airway inflammation and remodeling in vivo and in vitro. METHOD: Four groups of female BALB/c mice (control; ovalbumin [OVA]-sensitized and -challenged; dimethyl sulfoxide [DMSO]-treated OVA; and pranlukast-treated OVA) were examined. Lung pathology, cytokine production, and airway hyperresponsiveness (AHR) measurements were compared among these groups. A human fetal lung fibroblast HFL-1 cell line was used in the peribranchial fibrosis analysis. RESULTS: OVA-sensitized and -challenged mice exhibited allergic airway inflammation and significant increases in Th2 cytokines. Pranlukast-treated mice showed significant attenuation of allergic airway inflammation. The pranlukast treatment decreased AHR and attenuated airway remodeling to goblet cell hyperplasia, collagen deposition, α-smooth muscle actin expression, and pro-fibrotic gene expression. We further demonstrated that pranlukast not only inhibited transforming growth factor-beta 1 (TGF-ß1)-induced Smad signaling in human fetal lung fibroblast cells but also simultaneously reduced collagen synthesis and pro-fibrotic gene expression. CONCLUSIONS: The leukotriene receptor antagonist pranlukast can reduce airway inflammation and remodeling by inhibiting TGF-ß/Smad signaling in an OVA-sensitized and -challenged asthma mouse model, thus suppressing AHR.

Genetic diversity and phylogenetic analysis of newly discovered bat astroviruses in Korea.

Bats have been identified as a natural reservoir for several potentially zoonotic viruses. Recently, astroviruses have been reported in bats in many countries, but not Korea. We collected 363 bat samples from thirteen species at twenty-nine sites in Korea across 2016 and tested them for astrovirus. The detection of the RNA-dependent RNA polymerase (RdRp) gene in bat astroviruses was confirmed in thirty-four bats across four bat species in Korea: twenty-five from Miniopterus fuliginosusi, one from Myotis macrodactylus, four from M. petax, and four from Rhinolophus ferrumequinum. The highest detection rates for astrovirus were found in Sunchang (61.5%, 8/13 bats), and in the samples collected in April (63.2%, 12/19 bats). The amino acid identity of astroviral sequences identified from bat samples was ≥ 46.6%. More specifically, the amino acid identity within multiple clones from individual bats was ≥ 50.8%. Additionally, the phylogenetic topology between astroviruses from different bat families showed a close relationship. Furthermore, phylogenetic analysis of the partial ORF2 sequence of bat astroviruses was found to have a maximum similarity of 73.3-74.8% with available bat astrovirus sequences. These results indicate potential multiple-infection by several bat astrovirus species in individual bats, or hyperpolymorphism in the astrovirus strains, as well as the transmission of astroviruses across bat families; furthermore, our phylogenetic analysis of the partial ORF2 implied that a novel astrovirus may exist. However, the wide diversity of astroviral sequences appeared to have no significant correlation with bat species or the spatiotemporal distribution of Korean bat astroviruses.