Prevalence of sensitization to specific allergens in allergic patients in Beijing, China: A 7-year retrospective study.

BACKGROUND: Knowledge of the prevalence of common sensitizing allergens may aid in overall management of allergic disease in a specified area. OBJECTIVE: The aim of this study was to identify and analyse the prevalence of common inhaled and food sensitizing allergens in Beijing. METHODS: This was a retrospective study, analysing demographic data and serum sIgE antibody test results from 59057 outpatients who presented to Beijing TongRen Hospital, from January 2013 to December 2019. RESULTS: 28879 patients (48.9%) showed positive sIgE test results; with significantly more males aged under 16 years sensitized to at least one allergen than females, and most patients (53.62%) were sensitized to multiple allergens. The first inhaled sensitizing allergens was Artemisia grass (11910 (41.24%)); and the first food allergens was crab (3547 (12.28%)). For Artemisia sensitized patients, sIgE levels were mostly at level 5. The number of patients with ragweed allergy is increasing year by year. The detection rates for sIgE to Artemisia, common ragweed, and Humulus grass allergens were significantly higher in August and September. R package ggplot2 analysis, demonstrated strong correlations between tree allergens and common ragweed and Humulus grass allergens (phi coefficients = 0.50 and 0.46, respectively; both P < 0.01). CONCLUSIONS: The prevalence of sensitization to different allergens in Beijing showed Artemisia grass was the most commonly inhaled sensitizing allergen, and the number of patients with ragweed grass allergy was increasing by year.

PSK1 coordinates glucose metabolism and utilization and regulates energy-metabolism oscillation in Saccharomyces cerevisiae.

Energy-metabolism oscillations (EMO) are ultradian biological rhythms observed in in aerobic chemostat cultures of Saccharomyces cerevisiae. EMO regulates energy metabolism such as glucose, carbohydrate storage, O2 uptake, and CO2 production. PSK1 is a nutrient responsive protein kinase involved in regulation of glucose metabolism, sensory response to light, oxygen, and redox state. The aim of this investigation was to assess the function of PSK1 in regulation of EMO. The mRNA levels of PSK1 fluctuated in concert with EMO, and deletion of PSK1 resulted in unstable EMO with disappearance of the fluctuations and reduced amplitude, compared with the wild type. Furthermore, the mutant PSK1Δ showed downregulation of the synthesis and breakdown of glycogen with resultant decrease in glucose concentrations. The redox state represented by NADH also decreased in PSK1Δ compared with the wild type. These data suggest that PSK1 plays an important role in the regulation of energy metabolism and stabilizes ultradian biological rhythms. These results enhance our understanding of the mechanisms of biorhythms in the budding yeast.

Artemisia annua-sublingual immunotherapy for seasonal allergic rhinitis: A randomized controlled trial.

BACKGROUND: Artemisia annua is an important autumnal pollen allergen for seasonal allergic rhinitis (SAR) in northern China. To date, no study has investigated allergen immunotherapy with A annua. We aimed to investigate the efficacy and mechanisms underlying A annua-sublingual immunotherapy (SLIT). METHODS: This was a randomized, double-blind, placebo-controlled phase III clinical trial involving 71 SAR patients, randomized to SLIT with A annua extract (n = 47) or placebo (n = 24) for 32 weeks. Total nasal symptom score (TNSS; primary clinical end point) was evaluated at baseline (peak pollen phase (PPP) in the previous year), initiation of A annua-SLIT, 1st PPP during SLIT, end of SLIT and 2nd PPP during follow-up. Blood samples and nasal secretions were collected at beginning and after SLIT for assessment of T cells and inflammatory mediators. Safety was assessed according to adverse events (AEs) reported. RESULTS: Artemisia annua-SLIT significantly reduced TNSS to a greater level from baseline (from 9.45 ± 1.68 to 6.16 ± 2.27) than placebo (from 9.29 ± 2.09 to 9.05 ± 2.40) at the 1st PPP (P < .001) and sustained the improvement in symptoms throughout to the 2nd PPP. Preseasonal A annua-SLIT for 16 weeks significantly decreased Th2 cells, increased nTreg and Tr1 cells in blood; and increased cystatin 1 (CST1) in nasal secretion after 16 and 32 weeks compared with pretreatment. Overall, 17/47 patients experienced mild local AEs and 2 patients mild systemic AEs, after A annua-SLIT. CONCLUSION: Artemisia annua-SLIT is an efficacious and safe treatment in patients with A annua SAR.

A randomized controlled trial to assess adherence to allergic rhinitis treatment following a daily short message service (SMS) via the mobile phone.

BACKGROUND: Short message service (SMS) has been suggested as an effective method to improve adherence to medical therapy in some chronic diseases. However, data on the effects of SMS interventions to allergic rhinitis (AR) treatment is limited at present. We aimed to assess whether a daily SMS reminder could improve AR patients' adherence to medication and treatment outcomes. METHODS: Fifty outpatients with AR were randomized to either receive (SMS group) or not (control group) a daily SMS reminder on their cell phone to take intranasal corticosteroid treatment for 30 days. The primary study outcomes were self-reported adherence to medication, clinic attendance rate, and severity of AR symptoms using a visual analogue scale (VAS). Secondary outcomes were changes in nasal patency (minimum cross-sectional area, nasal cavity volume, and nasal airway resistance) and exhaled nasal nitric oxide levels. RESULTS: Self-reported adherence to medication in the SMS group (15/25, 60%), was significantly higher than in the control group (7/25, 28%, p = 0.02). Similarly, the clinic attendance rate in the SMS group (72%) was significantly higher than in the control group (40%, p = 0.02). Although the VAS score improved significantly from baseline in both study groups, the improvement in the SMS group was significantly greater than in the control group (4.38 ± 4.38 vs. 8.74 ± 6.54, p = 0.031). No significant differences were observed between the two groups for the secondary outcomes. CONCLUSIONS: A daily SMS reminder may be an effective intervention to improve adherence to medication and treatment outcomes in AR patients.

Main Airborne Pollen Species and Characteristics of Allergic Rhinitis Patients with Pollen-Related Allergies in 13 Northern Chinese Cities.

Background: Pollen allergies have a high prevalence in northern China, whereas, the types of pollen allergens and population characteristics among different regions remain unclear. Objective: To study the species and temporal distribution of the main allergenic pollen, as well as the characteristics of patients with pollen-related allergic rhinitis (AR) in different cities in northern China. Methods: Pollen data were obtained from pollen-monitoring stations in 13 cities of northern China between 2020 and 2021. Questionnaire surveys and allergen testing were conducted in 494 patients with pollen-related allergies from Beijing in Central, Shenyang in Northeast, and Xi'an in Northwest China. Results: In 13 cities of northern China, the main sources of pollen were cypress, poplar, elm, pine, birch and ash in spring, and mugwort, goosefoot, hop and ragweed in autumn. In Northwest China, the spring and autumn pollen periods started earlier and lasted longer than that in Central and Northeast China, and the pollen counts in autumn in was significantly higher than that in Central and Northeast China. Furthermore, the nasal, ocular and respiratory symptom and quality of life scores of AR patients in Northwest China were significantly higher than that in Central and Northeast China. 69.32-73.28% of patients had annual cost of anti-allergic medication between 500-5000 yuan. However, 40.93-48.86% of patients reported minor control of symptoms. Conclusion: Our results can be used as a basis for developing effective prevention and management measures for patients with pollen-related allergy in these regions, including timely pollen monitoring, patient guidance on protective measures, early intervention, and specific immunotherapy, to improve pollen-related allergy management.

Airborne pollen exposure and risk of hospital admission for allergic rhinitis in Beijing: A time-stratified case-crossover study.

BACKGROUND: Airborne pollen is a crucial risk factor in allergic rhinitis (AR). The severity of AR symptoms can vary based on pollen type and concentration. This study aimed to estimate the association between exposure to different pollen types and AR risk. METHODS: We obtained data from patients admitted to the Beijing Tongren Hospital for AR, and data on pollen concentration, meteorological factors, and fine particulate matter (PM2.5) from 13 districts in Beijing from 2016 to 2019. We used a time-stratified case-crossover study design and calculated odds ratios (ORs) related to the risk of AR associated with a 10 grain/1000 mm2 increase in total pollen concentrations for specific pollen types. A stratified analysis was conducted to assess whether the associations were varied by age and sex. RESULTS: The OR of AR associated with a 10 grain/1000 mm2 increase in the 7-day average pollen concentration was 1.014 (95% CI: 1.014, 1.015), 1.076 (95% CI: 1.070, 1.082), 1.024 (95% CI: 1.023, 1.025), 1.042 (95% CI: 1.039, 1.045), 1.142 (95% CI: 1.137, 1.147), 1.092 (95% CI: 1.088, 1.097), 1.046 (95% CI: 1.035, 1.058), and 1.026 (95% CI: 1.024, 1.028) for total pollen, Ulmus, Cupressaceae, Populus, Fraxinus, Pinus, Betula, and Artemisia, respectively. Both tree pollen (Ulmus, Cupressaceae, Populus, Fraxinus, Betula, and Pinus) and weed pollen (Artemisia, Chenopodium, and Humulus) were correlated with an increased risk of AR. These associations remained consistent across distinct subgroups defined by both age and sex. CONCLUSION: Exposure to pollen from trees and weeds might be associated with an increased risk of AR. This research provides valuable scientific support for both clinical practitioners and patients with AR regarding the hazards of pollen exposure.

Clinical characteristics and expression of thymic stromal lymphopoetin in eosinophilic and non-eosinophilic chronic rhinosinusitis.

OBJECTIVE: To evaluate the differences in clinical features and expression of cytokine thymic stromal lymphopoetin (TSLP) and its receptors in patients with eosinophilic and non-eosinophilic chronic rhinosinusitis (ECRS and NECRS). METHOD: 36 ECRS patients and 50 NECRS patients were evaluated for symptoms, nasal sinus computed tomography scanning, nasal endoscopy, skin prick test (SPT) positivity, and total IgE. Expression of TSLP and receptors in ethmoid sinus mucosa from the ECRS and NECRS groups were investigated by using immunohistochemical staining. RESULTS: ECRS patients demonstrated significantly higher scores of cough and hyposmia. 66.7% of ECRS patients also demonstrated nasal polyps, compared to 50% of NECRS patients, with significantly higher polyp endoscopy scores. 80.6% of ECRS patients demonstrated SPT positivity, compared to 14% of NECRS patients. The overall expression of TSLP, TSLP receptors and IL-7R was significantly greater in eosinophils in the mucosa of ECRS patients than in NECRS patients. The expression of TSLP and receptors in SPT-positive ECRS patients was significantly greater than in SPT-negative patients, with a significant correlation noted between the expression of TSLP and nasal polyp scores. CONCLUSION: The clinical manifestations of ECRS are likely to be influenced by atopic status of an individual and TSLP-mediated eosinophil infiltration of the rhinosinusoidal mucosa.

Impact of airborne pollen concentration and meteorological factors on the number of outpatients with allergic rhinitis.

The prevalence of allergic rhinitis (AR) caused by pollen allergen is high in northern China. This study analyzed the allergen detection results of patients with AR in Beijing Tongren Hospital from 2016 to 2019, and evaluated the association between AR and seasonal airborne pollen concentration and meteorological factors in Beijing, China. We found that AR patients caused by pollen accounted for 61.18% (16 793/27 449) in AR patients. Among them, Artemisia pollen sensitive patients accounted for 48.54% (13 325/27 449) of AR. We also found that the number of outpatients diagnosed with AR is strongly correlated with seasonal airborne pollen concentration and is influenced by meteorological factors, such as temperature and humidity. These results may help clinicians and healthcare workers to be prepared for this influx of outpatients in the relevant seasons.

Pollen grading prediction scale for patients with Artemisia pollen allergy in China: A 3-day moving predictive model.

BACKGROUND: Artemisia pollen is the most prevalent outdoor aeroallergen causing respiratory allergies in Beijing, China. Pollen allergen concentrations have a direct impact on the quality of life of those suffering from allergies. Artemisia pollen deposition grading predictions can provide early warning for the protection and treatment of patients as well as provide a scientific basis for allergen specific clinical immunotherapy. OBJECTIVE: To develop a model of Artemisia pollen grading to predict development in patients with pollen allergy. METHODS: Artemisia pollen data from four pollen monitoring stations in Beijing as well as the number of Artemisia pollen allergen serum specific immunoglobulin E positive cases in Beijing Tongren Hospital from 2014 to 2016 were used to develop a statistical model of pollen deposition and provide optimised threshold values. RESULTS: A logarithmic correlation existed between the number of patients with Artemisia pollen allergy and Artemisia pollen deposition, and the average pollen deposition for three consecutive days was most correlated with the number of allergic patients. Based on the threshold of the number of patients and the characteristics of Artemisia pollen, a five-stage pollen deposition grading model was developed to predict the degree of pollen allergy. CONCLUSIONS: Graded prediction of pollen deposition may help pollen allergic populations benefit from preventive interventions before onset.

Transforming growth factor-ß1 promotes nasal mucosal mast cell chemotaxis in murine experimental allergic rhinitis.

BACKGROUND: Recent studies have shown that transforming growth factor-ß(1) (TGF-ß(1)) plays an important role in the progression of allergic diseases. METHODS: Mouse models of allergic rhinitis were established by ovalbumin sensitization and challenge. Immunostaining was used to analyze the expression of TGF-ß(1) in the mouse nasal mucosa. A chemotaxis assay was conducted to analyze the impact of TGF-ß(1) stimulation on migration of mast cells differentiated from mouse bone marrow cells. Chemotaxis and Western blot analysis were further applied to investigate the pathways involved in mast cell migration induced by TGF-ß(1) stimulation. RESULTS: TGF-ß(1) expression was induced in allergic rhinitis and phosphorylated Smad2 was expressed in mast cells present in the nasal mucosa. TGF-ß(1) could induce migration of mast cells, but HTS466284, a TGF-ß receptor 1 kinase inhibitor, inhibited this chemotactic activity. After TGF-ß(1) stimulation, mast cell RhoA expression was significantly increased. TGF-ß(1)-induced mast cell chemotaxis could be inhibited by the RhoA inhibitor Tat-C3 and myosin light chain kinase inhibitor ML-7. CONCLUSION: TGF-ß(1) plays a major role in inducing the accumulation of mast cells in allergic rhinitis.

RIPK1 is a key factor in black carbon-induced cell death.

Air pollution is associated with increased morbidity and mortality and with cell death at a cellular level. However, the exact mechanism of particulate matter-induced cell death remains to be elucidated. The aim of the present in vitro study using human alveolar epithelial cells (A549) was to determine the cell death pathway(s) induced by black carbon (BC) and ozone oxidized-black carbon (O-BC). BC and O-BC induced A549 cell death and the cytotoxic effect was dose-dependent. Cell death was significantly abrogated by inhibitor of receptor protein interacting kinase 1 (RIPK1) but only mildly inhibited by apoptosis inhibitor and RIPK3. BC- and O-BC-treated cells showed RIPK1 and RIPK3 protein overexpression and high phosphorylated levels of these proteins, as well as detectable levels of caspase-8 active form. BC- and O-BC-triggered cell death was also fully rescued in A549 cells that under-expressed RIPK1 with RIPK1 siRNA. Our results indicated that BC and O-BC could induce cell death through a multitude of pathways including apoptotic and necroptotic pathways and that RIPK1 is the upstream signal protein of these cell death pathways, with an important role in the regulation of BC-induced cell death.

Quantification of Ceramsite Granules in Lightweight Concrete Panels through an Image Analysis Technique.

Ceramsite particles are an important component of lightweight ceramsite concrete wall panels, and the density of the aggregate is much lower than the density of the slurry. It is generally accepted that there are inhomogeneities in the distribution of ceramsite particles in wall panels. Ceramsite concrete wallboard material is a research hotspot in the field of fabricated building materials at home and abroad; however, there is no effective way to quantify their inhomogeneity. Based on the application of image recognition technology in concrete homogeneity, a method to quantitatively evaluate the distribution of light aggregates in wall panels was developed. Three commercial lightweight vitrified concrete wall panels were cut into 324 cubes. The four cut surfaces of each specimen were photographed to analyze the proportion of ceramsite particle area, while the density, ultrasonic pulse velocity, and compressive strength of the specimens were tested. The results demonstrated that the image analysis method could effectively describe the homogeneity of the panels. The proportion of particle area of aggregate in the section of the cube had a strong correlation with the compressive strength, ultrasonic pulse velocity, and density, and there was an obvious linear relationship with the height of the plate where the cube was located. Based on this, the correlation equations of the proportion of particle area of aggregate, density, ultrasonic pulse velocity, compressive strength, and the height where the specimen was located were proposed. The quantitative parameters of the relevant properties of the wall panels were also obtained: the maximum difference between the proportion of particle area of the aggregate was 24%, the maximum difference between the density at the top and bottom of the wall panels was 115 kg/m3, and the maximum difference in the strength reached 5 MPa.

The Durability of Recycled Fine Aggregate Concrete: A Review.

With the rapid development of urbanization, many new buildings are erected, and old ones are demolished and/or recycled. Thus, the reuse of building materials and improvements in reuse efficiency have become hot research topics. In recent years, scholars around the world have worked on improving recycle aggregates in concrete and broadening the scope of applications of recycled concrete. This paper reviews the findings of research on the effects of recycled fine aggregates (RFAs) on the permeability, drying shrinkage, carbonation, chloride ion penetration, acid resistance, and freeze-thaw resistance of concrete. The results show that the content of old mortar and the quality of recycled concrete are closely related to the durability of prepared RFA concrete. For example, the drying shrinkage value with a 100% RFA replacement rate is twice that of normal concrete, and the depth of carbonation increases by approximately 110%. Moreover, the durability of RFA concrete decreases as the RFA replacement rate and the water-cement ratio improve. Fortunately, the use of zeolite materials such as fly ash, silica fume, and meta kaolin as surface coatings for RFAs or as external admixtures for RFA concrete had a positive effect on durability. Furthermore, the proper mixing methods and/or recycled aggregates with optimized moisture content can further improve the durability of RFA concrete.

PSK2 coordinates glucose metabolism and utilization to maintain ultradian clock-coupled respiratory oscillation in Saccharomyces cerevisiae yeast.

Ultradian clock-coupled respiratory oscillation (UCRO) in an aerobic continuous culture of Saccharomyces cerevisiae S288C is principally regulated by control of certain redox reactions of energy metabolism. It is also modulated by the metabolism of storage carbohydrates during adaptation to environmental change. However, the mechanism of cell sensing and response to environmental nutrients in UCRO is unknown. The purpose of the present study was to determine the role of PSK2 kinase in UCRO in yeast. S. cerevisiae in culture showed oscillation in PSK2 mRNA levels with a definite phase relationship to the respiratory oscillation. Furthermore, inactivation of Psk2 by gene disruption severely affected UCRO and its decline to undetectable levels within 2days. In addition, the extracellular and intracellular glucose concentrations of PSK2 deletion mutants in culture were higher and lower, respectively, than those of the wild type. PSK2 mutant cells showed no alteration in redox state. Furthermore, the levels of storage carbohydrates such as glycogen and trehalose fluctuated in PSK2 mutants with attenuated amplitudes comparable to those in the wild type. The results indicated that PSK2 kinase is important for the uptake of glucose and regulation of storage-carbohydrate synthesis and hence the maintenance of an unperturbed continuously oscillating state.

Decreased expression of EBI3 and Foxp3 in CD4+CD25+ regulatory T cells in murine experimental allergic rhinitis.

BACKGROUND: Epstein-Barr virus-induced gene 3 (EBI3) is a widely expressed interleukin-12-related protein that plays a critical role in the regulation of effector T cells and inflammatory responses. METHODS: Allergic rhinitis (AR) was induced in mice by both intraperitoneal injection and intranasal administration of ovalbumin. By using immunohistochemical techniques, we investigated EBI3 expression in mouse spleens. The expressions of EBI3 and forkhead transcription factor 3 (Foxp3) in CD4+CD25+ regulatory T (T(reg)) cells isolated from spleens were assessed by flow cytometry. RNA extraction and RT-PCR were used to measure EBI3 and Foxp3 mRNA expression. RESULTS: EBI3 and Foxp3 were expressed mainly in the white pulp of the spleens. Flow cytometry analysis showed that EBI3 and Foxp3 coexpressed in mouse CD4+CD25+ T(reg) cells. Furthermore, RT-PCR and flow cytometry analysis showed that expression of both Foxp3 and EBI3 was reduced in CD4+CD25+ T(reg) cells in an AR mouse model compared with controls, but there was no difference in the frequency of CD4+CD25+ T(reg) cells. CONCLUSIONS: The deficiency in CD4+CD25+ T(reg) cell suppressive activity in AR is associated with the molecular mediators EBI3 and Foxp3.

Exposure to environmental black carbon exacerbates nasal epithelial inflammation via the reactive oxygen species (ROS)-nucleotide-binding, oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3)-caspase-1-interleukin 1ß (IL-1ß) pathway.

BACKGROUND: Allergic rhinitis(AR) is an increasing challenge to public health worldwide. Exposure to environmental black carbon (BC) is associated with increased risk of allergic rhinitis, but the molecular mechanisms underlying its toxicity have not been fully elucidated. The aims of the present study were therefore to determine the effect of BC on the expression of interleukin 1ß (IL-1ß) and to investigate the mechanism underlying BC-induced IL-1ß production in pollen-sensitized human nasal epithelial cells (hNECs). METHODS: Nasal mucosal samples collected from 10 patients undergoing nasal surgery were used to isolate and culture epithelial cells as air-liquid interface (ALI) cultures. Cultures exposed to BC ± pollen allergen for 24 hours were assessed for the presence of IL-1ß, the production of reactive oxygen species (ROS), and activation of the nucleotide-binding, oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Furthermore, the mechanisms underlying BC ± pollen allergen-induced IL-1ß in hNECs were evaluated. RESULTS: Exposure to BC significantly increased the production of IL-1ß and ROS and the expression of NLRP3 in hNECs, compared with control, all of which were significantly increased further by exposure to a combination of BC and pollen. Incubation of hNECs with N-acetyl-L-cysteine (NAC) significantly attenuated BC ± pollen-induced expression of ROS, NLRP3, and IL-1ß. NLRP3 and Caspase-1 inhibitors (MCC950 and YVAD) significantly inhibited IL-1ß expression and NLRP3 activation, but not NLRP3 expression following exposure to BC ± pollen. CONCLUSION: These findings suggest that exposure to BC and pollen can exaggerate oxidative stress and significantly increase the expression of IL-1ß in hNECs, and that this may involve a pathway integrating ROS-NLRP3-Caspase-1-IL-1ß signaling.

Assessment of changes in genetic transcriptome in nasal epithelial cells exposed to ozone-aged black carbon and pollen allergen by high-throughput transcriptomics.

BACKGROUND: Air pollution may be associated with increased airway responsiveness to allergens in allergic rhinitis (AR). Ozone-aged environmental black carbon (O3BC) is an important constituent of atmospheric particulate matter (PM), for which the mechanisms underlying its effects have not been fully elucidated in AR. The objective of the present study was to determine the O3BC and pollen-induced alterations in the transcriptome in human nasal epithelial cells (hNECs) in vitro. METHODS: hNECs from nasal epithelial mucosal samples of healthy individuals undergoing nasal surgery (turbinoplasty or septoplasty) were established as air-liquid interface (ALI) cultures and exposed to O3BC, pollen, or a combination of O3BC+ pollen. Changes in cell viability were analyzed by fluorescence and changes in the transcriptome by high-throughput RNA sequencing (RNA-seq). Several differentially expressed genes were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Enrichment analysis, based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database, was performed to determine major biological functions and pathways involved. RESULTS: Exposure to ≥ 50 µg/ml O3BC or 25 µg/ml O3BC+ 200 µg /ml pollen significantly decreased cell viability of the hNECs compared to control (p < 0.05) or 25 µg/ml O3BC alone (p < 0.05); whereas exposure to pollen alone did not alter cell viability at any concentration investigated. High-throughput RNA sequencing analysis indicated that there was significant difference in gene expression between pollen or O3BC alone and O3BC+ pollen exposed cells. Exposure to 200 µg/ml O3BC was associated with hypoxia stress response GO terms, whereas exposure to 25 µg/ml O3BC+ 200 µg/ml pollen was associated with inflammatory response GO terms; including regulation of neutrophil migration and chemotaxis, macrophage differentiation and chemotaxis, mast cell activation, and phagocytosis. KEGG pathway analysis indicated the top 10 upstream regulators to be IL1B, CSF1, CCL2, TLR2, LPL, IGF8, SPP1, CXCL8, FCER1G and IL1RN; of which expressions of inflammation-related genes IL1B, CSF1 and FCER1G were significantly increased. CONCLUSION: O3BC and pollen allergen combined exposure may induce innate immune and allergic inflammation in hNECs, and therefore potentially exacerbate the symptoms of AR in affected individuals.

TGF-beta signaling may play a role in the development of goblet cell hyperplasia in a mouse model of allergic rhinitis.

BACKGROUND: Transforming growth factor-beta (TGF-beta) levels are elevated in the nasal mucosa in allergic rhinitis. However, because TGF-beta is secreted extracellulary in latent complexes, it remains unclear whether the local TGF-beta expression actually drives active signaling and affects the pathophysiology of allergic rhinitis. The objective of this study is to investigate whether TGF-beta signaling is activated in allergic rhinitis and plays a role in the pathophysiology of allergic rhinitis. METHODS: An ovabumin (OVA)-sensitized and -nasally challenged mouse model of allergic rhinitis was established and phosphorylation of Smad2 in the nasal mucosa was examined by immunohistochemistry. In addition, the effects of the pharmacological inhibition of endogenous TGF-beta signaling on the allergic rhinitis model were histologically examined. Furthermore, phosphorylation of Smad2 in the nasal mucosa samples obtained from patients with allergic rhinitis was also evaluated. RESULTS: In the mouse model of allergic rhinitis, OVA challenge induced phosphorylation of Smad2 predominantly in epithelial cells in the nasal mucosa. In addition, the administration of an inhibitor of TGF-beta type I receptor kinase activity during OVA challenge suppressed goblet cell hyperplasia in the nasal mucosa. Furthermore, phosphorylated Smad2 expression increased in nasal epithelial cells in patients with allergic rhinitis. CONCLUSIONS: These results suggest that TGF-beta signaling is activated in epithelial cells in the nasal mucosa in allergic rhinitis and may contribute to the development of goblet cell hyperplasia.

Human trehalase is a stress responsive protein in Saccharomyces cerevisiae.

Three trehalases ATH1, NTH1, and NTH2 have been identified in Saccharomyces cerevisiae. ATH1, and NTH1 hydrolyze trehalose to glucose to provide energy and assist in recovery from stress. Human trehalase (TREH) is expressed in the intestine and kidney and probably hydrolyzes ingested trehalose in the intestine and acts as marker of renal tubular damage in kidney. Since trehalose is not present in circulation or kidney tubules, its renal effect suggests it has other yet unidentified actions. Here we examined the function of human trehalase in budding yeast. We constructed three yeast trehalase mutants (NTH1Delta, NTH2Delta, and ATH1Delta) and then transformed TREH into these mutants. NTH1Delta did not grow on media containing trehalose as the carbon source, and TREH did not rectify NTH1Delta dysfunction and also did not grow on trehalose medium, suggesting that TREH is not responsible for utilization of exogenous trehalose in yeast. In experiments involving exposure to heat, osmotic and oxidative stresses, NTH1Delta showed no recovery. Interestingly, ATH1Delta-TREH showed high sensitivity to all three stressors. ATH1Delta and NTH2Delta showed very low neutral trehalase activity and NTH1Delta did not show any neutral trehalase activity, and trehalose concentrations were higher. Increased neutral trehalase activity (equivalent to the wild type), reduction of trehalose content and brisk sensitivity to stressors were noted in TREH-ATH1Delta strain, but not in TREH-NTH1Delta or -NTH2Delta. Our results suggest that TREH acts as a stress-response protein in the kidney rather than involved in utilization of exogenous trehalose.

Transforming growth factor-beta activity in commercially available pasteurized cow milk provides protection against inflammation in mice.

Cow milk contains a large amount of an immunoregulatory cytokine, transforming growth factor-beta (TGFbeta). The present study investigated whether commercially available pasteurized cow milk retains TGFbeta activity both in vitro and in vivo. Some commercial cow milk increased TGFbeta/Smad-responsive reporter activity and induced Smad2 phosphorylation and the transcription of the TGFbeta/Smad target genes TGFbeta itself and Smad7 in vitro. Mice treated orally with 500 microL of cow milk containing TGFbeta (3 microg/L) daily for 2 wk had increased phosphorylation of Smad2 and TGFbeta and Smad7 mRNA expression in the intestine. These mice also had significantly greater serum TGFbeta concentrations than the mice treated orally with PBS. Furthermore, oral administration of 500 microL of cow milk containing TGFbeta (3 microg/L) daily for 2 wk before the induction of dextran sodium sulfate colitis and lipopolysaccharide-induced endotoxemia ameliorated tissue damage and mortality, respectively, in mice. These in vivo effects of cow milk were abrogated by the simultaneous administration of TGFbeta type I receptor kinase inhibitor with the cow milk, and they were not observed after the oral administration of cow's milk containing little TGFbeta. In humans, 1 oral challenge of 10 mL/kg cow milk containing TGFbeta (3 microg/L) increased the plasma TGFbeta concentrations at 4 h after the challenge. Thus, some commercially available pasteurized cow milk retains TGFbeta activity, which may be able to provide protection against experimental colitis and endotoxemia associated with increased intestinal and circulating TGFbeta levels.