The miR-9-5p/KLF5/IL-1ß Axis Regulates Airway Smooth Muscle Cell Proliferation and Apoptosis to Aggravate Airway Remodeling and Inflammation in Asthma.

The aim of this study was to investigate the underlying mechanism of miR-9-5p in airway smooth muscle cells (ASMCs) of asthmatic mice. An asthmatic mouse model was established through the intraperitoneal injection of ovalbumin. Histopathological changes in lung tissues of asthmatic mice were observed using HE staining. ASMCs was identified using immunofluorescence staining and cell morphology. The mRNA expressions of miR-9-5p, KLF5, and IL-1ß were measured using RT-qPCR. Additionally, CCK8 assay and flow cytometry were applied for ASMC proliferation and apoptosis, respectively. The protein levels of OPN, KLF5, and IL-1ß were assessed using western blotting. The results showed that miR-9-5p was abnormally downregulated in lung tissues and ASMCs of asthmatic mice. Dual-Luciferase Reporter Assay and Chromatin immunoprecipitation confirmed that miR-9-5p targeted KLF5 that bounds to IL-1ß promoter. Besides, miR-9-5p negatively regulated IL-1ß mRNA and protein level via KLF5. Moreover, miR-9-5p was found to positively regulate ASMC apoptosis, negatively regulate ASMC proliferation and OPN protein expression, albeit with partial reversal by KLF5. Mechanistically, the regulation of ASMC proliferation and apoptosis by miR-9-5p is achieved by targeting KLF5/IL-1ß axis.

Characteristics of dust mite sublingual immunotherapy-associated adverse events in the early phase.

Background: Few studies reported the characteristics of house dust mite (HDM) sublingual immunotherapy (SLIT) adverse events (AEs) during early phase treatment. The aim of this prospective study was mainly to explore the characteristics of AEs in allergic rhinitis (AR) patients during 6 months of HDM SLIT. Methods: A total of 242 patients with AR were enrolled in this study. Telephone follow-up and administration were conducted in the every week of the first month, the third month, and the sixth month of SLIT treatment. Furthermore, the early efficacy, AEs, and compliance were analyzed in our study. Results: Overall, 70.25% (170/242) of the AR patients completed the study, while 29.75% (72/242) of the AR patients failed to complete the whole 6 months of SLIT treatment process. On the whole, symptoms improved in 87.65% (149/170) of patients including 34.12% (58/170) well-controlled and 53.53% (91/170) partially controlled. The correlation analysis results showed that the treatment effect was negatively correlated with the age (r = -0.1614, P = 0.0355). The AEs mainly occurred in the first month, comprised of local rashes, gastrointestinal reactions, and itching of mouth and tongue. Subgroup analysis in the first month showed the itching of mouth and tongue, gastrointestinal reactions, fatigue, and other AEs in ≥14 years old group (14-65 years old, n = 42) were significant differences when compared with that in the <14 years old group (4-13 years old, n = 128, all P < 0.05). In the study, the main reasons for terminated immunotherapy were drug inaccessibility, loss of follow-up and long course of treatment. Conclusion: Patients with AR who received HDM SLIT revealed an early efficacy after 6 months, with AEs mostly occurred in the first month.

Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update.

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

Environmental and sensitization variations among asthma and/or rhinitis patients between 2008 and 2018 in China.

BACKGROUND: Little is known about the changes in allergen sensitization in China secondary to the environmental variations over the past decade. We aimed at investigating the variations in sensitization among asthma and/or rhinitis patients in China between 2008 and 2018. METHODS: This study analyzed cross-sectional data from national surveys conducted in China in 2008 and 2018. After finishing the questionnaire, participants underwent serum specific IgE measurements. A total of 2322 and 2798 patients were enrolled in 2008 and 2018, respectively. The significance of differences in sensitization rates among four regions of China were assessed. Correlation analysis was used to identify the associations of sensitization with climate change and planting of Artemisia desertorum between the two surveys. RESULTS: Compared with 2008, the general sensitization rate to mites significantly increased in 2018, which ranked highest among all tested allergens. Sensitization to pollens, especially Artemisia vulgaris, showed the greatest increase in the north. The annual mean temperature, rainfall and relative humidity in all four regions, and the Artemisia desertorum coverage in the northeastern area, increased significantly in 2018 as compared with 2008. From 2008 to 2018, an increase in Dermatophagoides pteronyssinus sensitization was significantly associated with an increase in relative humidity (r = 0.54, p = 0.037). The increase in A. vulgaris sensitization was significantly associated with the increase in the A. desertorum planting area (r = 0.67, p = 0.006) and with a decrease in rainfall (r = -0.59, p = 0.021). CONCLUSIONS: House dust mites remain the most important allergen in Chinese individuals with asthma and/or rhinitis. Pollen sensitization dramatically increased in northern China. Increases in sensitization to dust mites and Artemisia were related to the increases in humidity and planting area of A. desertorum.

Reduced CCR6+IL-17A+Treg Cells in Blood and CCR6-Dependent Accumulation of IL-17A+Treg Cells in Lungs of Patients With Allergic Asthma.

Human regulatory T (Treg) cells play a central role in controlling allergic inflammation in the airways. A reduced number of peripheral Treg cells and decreased suppressive function have been previously reported in the pathogenesis of allergic asthma. However, the characteristic role of specific Treg cell subsets and their mechanisms in the pathogenesis of allergic asthma remain unclear. In this study, we examined the proportion of different Treg cell subsets in both healthy subjects and patients with allergic asthma using flow cytometry and single-cell RNA sequencing. The migration function of the cells was compared using cell sorting and Transwell experiments. Furthermore, two allergen-challenged mouse models and a cell transfer experiment were used to examine the role of these Treg subsets. We found that the proportion of CD25+Foxp3+CD127- Treg cells in the peripheral blood of patients with allergic asthma was lower than in those of healthy subjects. Furthermore, the circulating Treg cells expressed lower levels of CCR6 and IL-17 compared with healthy subjects. The chemokine from the airway mucosa, CCL20, was abundantly expressed, and Transwell experiments further proved that this chemokine promoted CCR6+ Treg cell migration in vitro. A mouse model induced by house dust mite (HDM) revealed that the number of CCR6+ Treg cells in the lung tissue increased remarkably. The incidence of allergic asthma may be related to an increase in Treg cells secreting IL-17 in the lung tissue. Recruited CCR6+ Treg cells are likely to differentiate into Th17-like cells under the Th17 environment present in the lungs. IL-17 derived from Th17-like cells could be associated with the pathology of allergic asthma by promoting Th17 responses, thereby favoring HDM-induced asthma exacerbations.

Quercetin inhibits proliferation of and induces apoptosis in non-small-cell lung carcinoma via the lncRNA SNHG7/miR-34a-5p pathway.

OBJECTIVE: To determine the role of quercetin in non-small cell lung carcinoma (NSCLC) and the biological outcomes using transfection experiments. MATERIALS AND METHODS: Real-time reverse transcription-PCR and data collection were performed to determine lncRNA and miRNA levels. Transwell assay was performed to assess the invasion ability of cells. Apoptosis of cells digested with trypsin was determined using the Annexin V-FITC kit. Luciferase activity was determined using the luciferase reporter gene system. Cell viability was tested using the Cell Counting Kit-8 assay. A xenograft mouse model was established to investigate the effects of quercetin on tumor growth. RESULTS: The expression levels of the long non-coding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) were elevated in NSCLC cells, and the expression levels of the microRNA miR-34a-5p were decreased compared with those in normal cells. Further investigation revealed that quercetin decreased SNHG7 and elevated miR-34a-5p levels in NSCLC cells (p < .05). The luciferase reporter gene assay, RNA-binding protein immunoprecipitation assay, and transfection experiments revealed target-binding sequences between SNHG7 and miR-34a-5p. Overexpression of SNHG7 or miR-34a-5p inhibitor promoted NSCLC cell proliferation and accelerated tumor cell growth and metastasis. The therapeutic effect of quercetin on NSCLC cells was counteracted by co-transfection of SNHG7 mimic or miR-34a-5p inhibitor. Quercetin inhibited the survival, proliferation, migration, and invasion of NSCLC cells and enhanced their apoptosis. Using the mouse model, quercetin was shown to inhibit tumor growth. CONCLUSIONS: Quercetin inhibits the proliferation and induces apoptosis of NSCLC cells by mediating signaling via the lncRNA SNHG7/miR-34a-5p pathway.

EIF3m promotes the malignant phenotype of lung adenocarcinoma by the up-regulation of oncogene CAPRIN1.

EIF3m is the latest identified subunit of the eukaryotic translation initiation factor 3 (eIF3), however, its function in malignant tumor is rarely reported. In the current work, we observed that EIF3m was aberrant over-expressed in lung adenocarcinoma (LADC) tissues and cell lines, and the increased EIF3m level was closely related to the poor clinical outcomes of the LADC patients. The gain- and loss-of-function assays demonstrated the proto-oncogenetic potential of EIF3m in vitro and in vivo. EIF3m induced-malignant phenotype was partly mediated by the up-regulation of CAPRIN1. The biochemical analysis showed that EIF3m could bind to the 5'UTR of CAPRIN1 and positively modulate its expression at the post-transcription level. Furthermore, we identified the interaction between EIF3m and the deubiquitinase UCHL5, which stabilized and promoted the accumulation of EIF3m in LADC cells. In summary, our findings extended the knowledge about the EIF3m function and highlight the roles of the UCHL5/EIF3m/CAPRIN1 axis during the progression of LADC.

A New Therapeutic Strategy Targeting Protein Deacetylation for Spinal Cord Injury.

Lysine acetylation is a post-translational modification that regulates a diversity of biological processes. However, its implication in spinal cord injury (SCI) remains unclear. Here we investigated the acetylation events in injured spinal cords on a proteomic scale for the first time. Additionally, whether promoting acetylation could mitigate SCI was evaluated. A total of 268 differentially acetylated peptides were identified. Among them, 2 peptides were up-acetylated and 141 peptides were down-acetylated in the injured spinal cord tissues (Fold change >2 and P < 0.05). There were also 116 unique acetylated peptides in the sham group and 9 unique acetylated peptides in the SCI group. Functional enrichment analysis revealed that differently acetylated proteins were involved in multiple cellular processes and metabolic processes. Kyoto Encyclopaedia of Genes and Genomes analysis showed that several pathways, including cGMP-PKG signaling pathway and hypoxia-inducible factor-1 (HIF-1) signaling pathway, were predominantly presented. Moreover, promoting acetylation using glycerol triacetate (GTA) showed a therapeutic effect on SCI, with improved Basso-Beattie-Bresnahan scores and histologic morphology, and decreased neuronal apoptosis and inflammation. In conclusion, our data indicated that protein deacetylation might play crucial roles in the development of secondary injury of SCI, and promoting acetylation by GTA effectively mitigated SCI. Our data not only enhance our understanding on acetylproteome dataset in the spinal cord tissues, but also provide novel insights for the treatment of SCI.

Sulfur dioxide exposure reduces the quantity of CD19+ cells and causes nasal epithelial injury in rats.

BACKGROUND: Reactive airway dysfunction syndrome (RADS), also called irritant-induced asthma, is a type of occupational asthma that can occur within a very short period of latency. The study sought to investigate the influence of sulfur dioxide (SO2) exposure on CD19+ cells and nasal epithelial injury. METHODS: We investigated the effects of SO2 on CD19 expression and morphological changes of nasal epithelia in rats. In the study, 20 rats were randomly divided into the SO2 exposure group that were exposed to 600 ppm SO2, 2 h/day for consecutive 7 days, and the control group that were exposed to filtered air). RESULTS: Inhalation of high concentration of SO2significantly reduced CD19 expression at both the mRNA transcript and protein levels, and reduced the percentages of CD19+ cells and CD19+/CD23+ cells in the nasal septum. However, inhalation of high concentration of SO2 did not affect immunoglobulin (Ig) G, IgA and IgE levels in the serum and nasal septum. More importantly, SO2 exposure also caused mild structural changes of the nasal septum. CONCLUSION: Our results reveal that inhalation of a high concentration of SO2 reduces CD19 expression and causes structural change of the nasal septum in rats.

Natural helper cells mediate respiratory syncytial virus-induced airway inflammation by producing type 2 cytokines in an IL-33-dependent manner.

AIM: Type 2 cytokine production during respiratory virus infection is considered to be linked with asthma exacerbation. As potent Th2 cytokine producers, natural helper (NH) cells play a key role in influenza virus-induced airway hyper-responsiveness. However, it is unclear whether NH cells contribute to respiratory syncytial virus (RSV)-induced airway inflammation, and how the cytokine profile in NH cells is changed during RSV infection. METHODS: BALB/c mice were infected intranasally with RSV. The number of NH cells in lungs was detected by flow cytometry. The expression of cytokine mRNAs was performed by real-time RT-PCR. Cytokines levels were determined by ELISA. RESULTS: Following intranasal infection with RSV, BALB/c mice showed an increase in the expression of mRNAs for Th2-like cytokines in NH cells. Furthermore, adoptive transfer of pulmonary NH cells resulted in a massive infiltration of mononuclear cells, in particular eosinophils and neutrophils in lungs, in parallel with an augmented production of Th2-associated cytokines, such as IL-4, IL-5 and IL-10 in bronchoalveolar lavage fluids, providing convincing evidence that NH cells contribute to RSV-induced lung pathogenesis by producing type 2 cytokines. It should be noted that blocking IL-33 with antibody can diminish the absolute number of pulmonary NH cells and the relative expression of mRNAs for type 2 cytokines in pulmonary NH cells, suggesting that IL-33 is necessary for activating Th2-type NH cells. CONCLUSION: These results reveal that pulmonary NH cells might participate in RSV-induced airway inflammation by producing large quality of type 2 cytokines in an IL-33-dependent manner.

Role of γδ T cells in exacerbated airway inflammation during reinfection of neonatally primed mice in adulthood.

Age at primary infection with respiratory syncytial virus (RSV) is a crucial factor in determining the outcome of reinfection. However, how neonatal RSV infection affects the immune system and renders the host more susceptible to reinfection in later life is poorly understood. In the present study, by using BALB/c mice that were first infected with RSV as neonates, the role of γδ T cells in the development of airway inflammation during reinfection in adulthood was investigated. We found that neonatal RSV infection resulted in an aggravated infiltration of mononuclear cells in bronchoalveolar lavage (BAL) fluids, in parallel with a significant increase in the levels of type 2 cytokines in lungs on day 4 after reinfection. Since the numbers of total γδ T cells as well as activated γδ T cells, particularly IL-4-, IL-5-, and IL-13-producing γδ T cells, were enhanced markedly in the lungs of neonatally primed mice, we speculate that γδ T cells might participate in the augmented airway inflammation seen during reinfection. Indeed, depletion of γδ T cells attenuated the severity of lung histopathology during reinfection. Meanwhile, treatment of neonatal mice with anti-TCRδ mAb diminished not only the numbers of neutrophils, eosinophils, and lymphocytes, but also the levels of IL-4, IL-5, and IL-13 in the lungs after reinfection in adulthood, suggesting that γδ T cells, particularly Th2-type γδ T cells might play a critical role in exacerbating the pulmonary tissue pathology during reinfection of adult mice that were first infected as neonates.

Up-regulated expression of substance P in CD8+ T cells and NK1R on monocytes of atopic dermatitis.

BACKGROUND: Large numbers of CD8+ T cells were observed in atopic dermatitis (AD) skin, and monocytes from AD patients showed increased prostaglandin E2 production. However, little is known about the expression of substance P (SP) and its receptor NK1R in blood leukocytes of patients with AD. OBJECTIVE: To explore the expression of SP and NK1R in leukocytes of AD and the influence of allergens on SP and NK1R expression. METHODS: The expression levels of SP and NK1R in patients with AD were examined by flow cytometry, ELISA and a mouse AD model. RESULTS: The plasma SP level was 4.9-fold higher in patients with AD than in HC subjects. Both the percentage of SP expression in the population and mean fluorescence intensity (MFI) of SP expression were elevated in CD8+ T cells in the blood of AD patients. However, both the CD14+NK1R+ population and MFI of NK1R expression on CD14+ cells were enhanced in the blood of AD patients. Allergens ASWE, HDME and PPE failed to up-regulate SP expression in CD8+ T cells. However, allergens ASWE and HDME both enhanced NK1R expression on CD14+ blood leukocytes regardless of AD or HC subjects. OVA-sensitized AD mice showed an elevated proportion and MFI of SP-expressing CD8+ T cells in the blood, which agrees with the SP expression situation in human AD blood. Injection of SP into mouse skin did not up-regulate NK1R expression on monocytes. CONCLUSIONS: An elevated plasma SP level, up-regulated expression of SP and NK1R indicate that the SP/NK1R complex is important in the development of AD. Therefore, SP and NK1R antagonist or blocker agents may help to treat patients with AD. Trial registration Registration number: ChiCTR-BOC-16010279; Registration date: Dec., 28, 2016; retrospectively registered.

Macrophages produce IL-33 by activating MAPK signaling pathway during RSV infection.

It has been reported that RSV infection can enhance IL-33 production in lung macrophages. However, little is known about specific signaling pathways for activation of macrophages during RSV infection. In the present study, by using real-time RT-PCR as well as western blot assay, it became clear that RSV infection can enhance not only the expression of mRNAs for MAPK molecules (including p38, JNK1/2, and ERK1/2), but also the levels of MAPK proteins in lung macrophages as well as RAW264.7 cells. Furthermore, infection with RSV resulted in an increased level of phosphorylated MAPK proteins in RAW264.7 cells, suggesting that MAPK signaling pathway may participate in the process of RSV-induced IL-33 secretion by macrophages. In fact, the elevated production of IL-33 in RAW264.7 was attenuated significantly by pretreatment of the cells with special MAPK inhibitor before RSV infection, further confirming the function of MAPKs pathway in RSV-induced IL-33 production in macrophages. In contrast, the expression of NF-κB mRNA as well as the production of NF-κB protein in lung macrophages and RAW264.7 cells was not enhanced markedly after RSV infection. Moreover, RSV infection failed to induce the phosphorylation of NF-κB in RAW264.7 cells, suggesting that NF-κB signaling pathway may be not involved in RSV-induced IL-33 production in macrophages. Conclusion, these results indicate that RSV-induced production of IL-33 in macrophages is dependent on the activation of MAPK signaling pathway.

The significance of the levels of IL-4, IL-31 and TLSP in patients with asthma and/or rhinitis.

AIM: To investigate the clinical significance of the levels of IL-4, IL-33 and thymic stromal lymphopoietin (TLSP) in patients with asthma and/or rhinitis, then do the simple verification in animals. METHODS: Levels of IL-4 IL-31, IL-33 and TLSP were detected by ELISA and real-time PCR in 64 asthma patients (sIgE[+]: 32 cases, sIgE[-]: 32 cases), 64 rhinitis patients (sIgE[+]: 32 cases, sIgE[-]: 32 cases), 64 asthma complicated with allergic rhinitis patients (sIgE[+]: 32 cases, sIgE[-]: 32 cases) and 32 healthy controls. Then we detected the IL-4, IL-31, IL-33 and TLSP in the sensitized mice. RESULTS: Results showed that levels of IL-4, IL-31, IL-33 and TSLP in asthma and rhinitis patients, and those complicated with allergic rhinitis, had significant differences compared with the control group (p < 0.05). It was found that the indicators of mugwort and dust mite allergic patients were significantly higher than that of other allergic patients (p < 0.05). We got the same tendency in in vivo experiments. CONCLUSION: IL-4, IL-31, IL-33 and TSLP may be involved in the pathogenesis of asthma and rhinitis; dust mite and mugwort allergy could increase them significantly.

Natural helper cells are associated with the exacerbated airway inflammation seen during RSV reinfection of neonatally primed mice.

Infection with respiratory syncytial virus (RSV) in neonatal mice causes more aggressive airway disease when the mice are reinfected with the same virus as adults. However, the underlying mechanisms responsible for this phenomenon are not entirely defined. Natural helper (NH) cells are considered a key factor for virus-induced or exacerbated airway inflammation and airway hyper-responsiveness by producing type 2 cytokines. To confirm whether NH cells are involved in the aggravated lung pathology seen during reinfection, BALB/c mice were initially infected as neonates and reinfected in adulthood. We observed that neonatal RSV infection resulted in an enhanced infiltration of eosinophils and neutrophils in the lungs, in parallel with a significant increase in the levels of IL-5 and IL-13 in bronchoalveolar lavage fluids on day 2 after reinfection. It seems likely that pulmonary NH cells may play a role in the occurrence, since mice first infected at 1wk of age developed an additional increase in the number of NH cells as well as IL-5- and IL-13-producing NH cells in the lungs than those first infected as young adults. In fact, an elevated expression of mRNAs for IL-5 and IL-13 in pulmonary NH cells was detected in mice first infected as neonates. Furthermore, adoptive transfer of NH cells into neonatal mice was able to boost eosinophilic infiltration as well as the production of type 2 cytokines in the lungs after reinfection at adulthood. In contrast, the expression of mRNA for the type 1 cytokine IFN-γ was down-regulated markedly by adoptive transfer of NH cells. Thus, these results suggest that Th2-type NH cells may play a role in the exacerbated airway inflammation seen during RSV reinfection of neonatally primed mice.

[Evaluation of long-term effect for house dust mite subcutaneous immunotherapy for patients with allergic rhinitis].

OBJECTIVE: To evaluate the long-term effect of house dust mite subcutaneous immunotherapy (SCIT) in patients with allergic rhinitis (AR). METHODS: A total of 102 patients with allergic rhinitis (not associated asthma) were recruited into the study. These patients were randomly divided into two groups: SCIT group and ST (symptomatic therapy) group. The patients were investigated for SCIT with standardized allergen vaccine for 3 years or no SIT only symptomatic therapy respectively. After the termination of SCIT, these patients were followed-up continuously for another 2 years. The therapeutic evaluation index included: rhinitis symptoms score, drug score, skin prick test, serum specific IgE (sIgE), as well as the number of development of asthma and the new sensitization. SPSS 11.0 software was used to analyze the data. RESULTS: Clinical symptom scores, drug scores, and skin test result all improved significantly after the treatment with SCIT compared to SCIT before and ST group (P < 0.01). Two years after the termination of SCIT, the same parameters showed no significant difference compared to 3 years before (P > 0.05). No rhinitis patients in SCIT group developed to asthma, only 4.7% of patients had been found to have new allergen. In the meantime, 22.0% of the patients with rhinitis in ST group developed asthma, and 41.5% patients were found to have new allergen. No severe adverse events occurred. CONCLUSIONS: The symptoms of the patients with allergic rhinitis were obviously improved by SCIT and a long-term curative effect could be maintained. It should be early applicated, which could prevent allergic rhinitis developed to asthma.

Ectopic expressed miR-203 contributes to chronic obstructive pulmonary disease via targeting TAK1 and PIK3CA.

MiRNA is a group of powerful short non-coding RNAs that suppress the expression of protein coding genes by targeting to the 3'UTRs of mRNAs. Some researchers have detected the miRNAs expression profile in tissue and blood samples of chronic obstructive pulmonary disease (COPD) patients recently. Several disturbed miRNAs were found to be related to COPD; however, the mechanisms were still well understood. In this study, we first detected the expression of 11 candidate miRNAs in the lung samples of COPD patients, non-COPD smokers and non-smock controls. We found that the expression of miR-181a, miR-203, miR-338, miR-1 and miR-199a was altered compared with control. Subsequently, we detected these five miRNAs expression in the blood samples of the participants. A significant higher expression of miR-203 was found in the blood samples of smokers and COPD patients. Predicted by bioinformatics tools and confirmed by luciferase assay and western blot, we demonstrated that TAK1 and PIK3CA are two direct targets of miR-203. Furthermore, we detected a lower p-IκBα and p-p65 level in the bronchial/tracheal epithelial cells from COPD patients compared with the cells from healthy controls, when stimulated by LPS. The concentration of TNF-α and IL-6 in the medium from bronchial/tracheal epithelial cells from COPD patients is also lower. Meanwhile, the miR-203 level was down-regulated significantly in the control cells, but non-significant change in the cells from COPD patients. miR-203 represses NF-κB signaling via targeting TAK1 and PI3KCA and miR-203 overexpression may contribute to the COPD initiation.

[Effect evaluation of allergen specific immunotherapy in patients with allergic rhinitis and asthma].

OBJECTIVE: To evaluate the effect of allergen specific immunotherapy (SIT) in patients with allergic rhinitis and asthma. METHOD A total of 68 patients with allergic rhinitis and asthma sensitized to dust mite were recruited into the study. They were randomly divided into two groups: SIT group n = 34 and symptomatic therapy (ST) group: n = 34. Patients in ST group received medication to treat, the symptoms, patients in SIT group received medication and 3 years of standardized allergen vaccine therapy. Evaluation index of therapy includes: rhinitis symptoms score, asthma symptoms score, drug score, skin prick test, serum specificity IgE (sIgE) , peripheral eosinophil (Eos) counting, lung function. The new sensitinogen rate was also assessed. RESULT: Clinical symptom scores, drug scores, lung function, blood eosinophil numbers and skin test result were all improved significantly after 3-year treatment in SIT group compared to those in ST group (P < 0.01). Although the level of serum slgE was decreased,there exited no statistic diferences between two groups. Only 8.8% patients have the new sensitization in SIT group, and 52.9% in ST group. There were no serious adverse reactions in treatment process. CONCLUSION: SIT for patients with AR and asthma can obtain excellent clinical efficacy.

[Efficacy evaluation of standardized dust mite allergen specific immunotherapy to patients of allergic rhinitis].

OBJECTIVE: To evaluate the efficacy of mite allergen specific immunotherapy (SIT) to patients of allergic rhinitis. METHOD: A total of 102 patients with mite allergy were recruited into the study. They were randomly divided into two groups: SIT group (n = 51) and ST (symptomatic therapy) group (n = 51). They were given SIT with standardized allergen vaccine for 3 years or only symptomatic therapy respectively. Observation items include: rhinitis symptom scores, drug score, skin prick test result, serum specificity IgE (sIgE), peripheral eosinophil counting. The development of asthma and new allergens sensitization was also assessed. RESULT: The blood eosinophil numbers, skin test index, rhinitis symptom scores and drug scores were all decreased significantly after the treatment with SIT for 3 years compared to that of ST group (P < 0.01). Although the level of serum slgE was decreased, no statistic diferences were found. No patients developed asthma in SIT group, and only 2.1% of patients had new allergen sensitization; 17.4% of those in ST group developed asthma, 32.6% had new sensitization. No severe adverse events occurred. CONCLUSION: Keeping long-term SIT is effective and safe for patients with allergic rhinitis induced by mite, which can also prevent new allergen sensitization and development for asthma.