Efficacy and safety of omalizumab combined with allergen immunotherapy in children with moderate to severe allergic asthma.

KEY POINTS: Omalizumab enables children who are intolerant to AIT to initiate AIT successfully. Combination therapy better improves asthma and rhinitis symptoms, FeNO, and lung function compared to single SCIT or omalizumab treatment. Combination therapy reduces the incidence of adverse reactions during the initial phase of SCIT and enhances its safety.

Synthetic routes and clinical application of new drugs approved by EMA during 2023.

In 2023, the European Medicines Agency (EMA) granted approval to 77 new molecular entities (NMEs), consisting of 45 new chemical entities (NCEs) and 32 new biological entities (NBEs). These pharmacological agents encompass a broad spectrum of therapeutic domains, including oncology, cardiology, dermatology, diagnostic medicine, endocrinology, gastroenterology and hepatology, metabolic disorders, and neurology. Among the 77 approved pharmaceuticals, three received accelerated review status, and 17 (22 %) were granted orphan drug designation for the treatment of rare diseases. This review provides an overview of the clinical applications and synthetic routes of 42 newly approved NCEs by the EMA in 2023. The objective is to offer a comprehensive understanding of the synthetic approaches used in the development of these drug molecules, thereby inspiring the creation of novel, efficient, and applicable synthetic methodologies.

Synthetic approaches and clinical application of representative small-molecule inhibitors of phosphodiesterase.

Phosphodiesterases (PDEs) constitute a family of enzymes that play a pivotal role in the regulation of intracellular levels of cyclic nucleotides, including cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Dysregulation of PDE activity has been implicated in diverse pathological conditions encompassing cardiovascular disorders, pulmonary diseases, and neurological disorders. Small-molecule inhibitors targeting PDEs have emerged as promising therapeutic agents for the treatment of these ailments, some of which have been approved for their clinical use. Despite their success, challenges such as resistance mechanisms and off-target effects persist, urging continuous research for the development of next-generation PDE inhibitors. The objective of this review is to provide an overview of the synthesis and clinical application of representative approved small-molecule PDE inhibitors, with the aim of offering guidance for further advancements in the development of novel PDE inhibitors.

FOXK2 facilitates the airway remodeling during chronic asthma by promoting glycolysis in a SIRT2-dependent manner.

Asthma is a chronic pulmonary disease with the worldwide prevalence. The structural alterations of airway walls, termed as "airway remodeling", are documented as the core contributor to the airway dysfunction during chronic asthma. Forkhead box transcription factor FOXK2 is a critical regulator of glycolysis, a metabolic reprogramming pathway linked to pulmonary fibrosis. However, the role of FOXK2 in asthma waits further explored. In this study, the chronic asthmatic mice were induced via ovalbumin (OVA) sensitization and repetitive OVA challenge. FOXK2 was upregulated in the lungs of OVA mice and downregulated after adenovirus-mediated FOXK2 silencing. The lung inflammation, peribronchial collagen deposition, and glycolysis in OVA mice were obviously attenuated after FOXK2 knockdown. Besides, the expressions of FOXK2 and SIRT2 in human bronchial epithelial cells (BEAS-2B) were increasingly upregulated upon TGF-ß1 stimulation and downregulated after FOXK2 knockdown. Moreover, the functional loss of FOXK2 remarkably suppressed TGF-ß1-induced epithelial-mesenchymal transition (EMT) and glycolysis in BEAS-2B cells, as manifested by the altered expressions of EMT markers and glycolysis enzymes. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) inhibited the EMT in TGF-ß1-induced cells, making glycolysis a driver of EMT. The binding of FOXK2 to SIRT2 was validated, and SIRT2 overexpression blocked the FOXK2 knockdown-mediated inhibition of EMT and glycolysis in TGF-ß1-treated cells, which suggests that FOXK2 regulates EMT and glycolysis in TGF-ß1-treated cells in a SIRT2-dependnet manner. Collectively, this study highlights the protective effect of FOXK2 knockdown on airway remodeling during chronic asthma.

Long-term noise exposure and cause-specific mortality in chronic respiratory diseases, considering the modifying effect of air pollution.

BACKGROUND: Chronic respiratory diseases (CRDs) are among the top three causes of human mortality. The relationship between modifiable environmental risk factor of noise and risk of mortality in CRDs is unclear. We investigated the longitudinal association between environmental noise exposure and cause-specific mortality in individuals with CRDs, considering the modifying effect of air pollution. METHODS: Residential noise exposure was modelled using Common Noise Assessment Methods in Europe. Information on death causes were acquired from death registry data. Cox proportional-hazards models were used to estimate effect sizes. RESULTS: Among 41,222 participants selected from UK Biobank with CRDs in baseline, a total of 3618 death cases occurred during an average follow-up of 12 years with mortality density of 7.16 per 1000 person years. Exposure with highest noise level (> percentile 90) were associated with 22 % (Hazard ratio [HR] = 1.22, 95 % confidence interval [CI]: 1.05, 1.42), 71 % (HR = 1.71, 95 % CI: 1.14, 2.56), and 84 % (HR = 1.84, 95 % CI: 1.10, 3.07) increased risks for all-cause, respiratory disease (RD)-cause, and COPD-cause mortalities, separately. Both multiplicative and additive interactions was found between air pollution and noise with the risk of RD-cause mortality. Participants with high air pollution and noise exposure were associated with a 101 % (HR = 2.01, 95 % CI: 1.10, 3.66) increased risk of RD-cause mortality. CONCLUSION: It is imperative to mitigate noise exposure as a preventive measure against incident mortality in individuals with CRDs.

Synthetic approaches and application of representative clinically approved fluorine-enriched anti-cancer medications.

Fluorine possesses distinctive chemical characteristics, such as its strong electron-withdrawing ability and small atomic size, which render it an invaluable asset in the design and optimization of pharmaceuticals. The utilization of fluorine-enriched medications for combating cancer has emerged as a prominent approach in medicinal chemistry and drug discovery, offering improved clinical outcomes and enhanced pharmacological properties. This comprehensive review explores the synthetic approaches and clinical applications of approved 22 representative fluorinated anti-cancer drugs from 2019 to present, shedding light on their historical development, brand names, drug target activity, mechanism of action, preclinical pharmacodynamics, clinical efficacy, and toxicity. Additionally, the review provides an extensive analysis of the representative synthetic techniques employed. Overall, this review emphasizes the significance of incorporating fluorine chemistry into anti-cancer drug research while highlighting promising future prospects for exploring compounds enriched with fluorine in the battle against cancer.

Synthetic routes and clinical application of Small-Molecule HER2 inhibitors for cancer therapy.

This comprehensive review undertakes a meticulous scrutiny of the synthesis and clinical applications pertaining to small-molecule tyrosine kinase inhibitors (TKIs) directed towards the human epidermal growth factor receptor 2 (HER2), a pivotal protagonist in the pathogenesis of cancer. Focused on compounds like lapatinib, neratinib, and tucatinib, the review delves into the intricate synthesis strategies, emphasizing the challenges associated with their structural complexity. The clinical utilization of HER2 TKIs underscores noteworthy strides in the therapeutic landscape for HER2-positive breast and gastric malignancies. Lapatinib, a dual HER2/ epidermal growth factor receptor (EGFR) inhibitor, has demonstrated efficacy in combination therapies, addressing the need for overcoming resistance mechanisms. Neratinib, an irreversible HER2 inhibitor, presents a promising avenue for patients with refractory tumors. Tucatinib, strategically engineered to traverse the blood-brain barrier, epitomizes a groundbreaking advancement in the management of metastatic HER2-positive breast cancer manifesting cerebral involvement. Despite their success, challenges such as resistance mechanisms and off-target effects persist, urging continuous research for the development of next-generation HER2 TKIs. This comprehensive review serves as a valuable resource for pharmaceutical scientists, offering insights into the synthetic intricacies and clinical impact of small-molecule TKIs targeting HER2.

Safety of subcutaneous immunotherapy with Novo-Helisen-Depot in the children: a retrospective analysis from a single center in Northern China.

Background: Little is known about the safety of mite extract product Novo-Helisen Depot (NHD) as subcutaneous immunotherapy (SCIT) in the children with mite allergy especially immediate/late local reaction (LRs). Methods: We conducted a retrospective study analyzing the adverse events of the children undergoing subcutaneous immunotherapy with NHD. Adverse events included local and systemic adverse reactions (SRs) at the very early and late stage. The correlation of the basic characteristics, laboratory analysis results, LRs and SRs were analyzed. Results: Two hundred and eighty-seven patients received at least 15 months of subcutaneous immunotherapy with NHD were included in the analysis. Skin-prick testing (SPT) results of D. pteronyssinus was associated with an increased risk of immediate LRs in build-up phase (OR = 1.53, 95% CI: 1.02, 2.37) and delayed LRs in maintenance phase (OR = 1.58, 95% CI: 1.05, 2.46), while SPT results of D. farinae was associated with an increased risk of SRs (OR = 3.22, 95% CI: 1.17, 10.00) and severe SRs (OR = 7.68, 95% CI: 1.13, 109.50). Serum IgE level of D. pteronyssinus was associated with an increased risk of SRs (OR = 1.01, 95% CI: 1.00, 1.03). Patients with both asthma and allergic rhinitis was associated with an increased risk of SR, and severe SRs (P < 0.05). Conclusion: NHD as SCIT is safe. The children with higher SPT level with D. farinae or D. pteronyssinus, higher serum IgE level of D. pteronyssinus, children with both asthma and allergic rhinitis, and the children with treatment interruption had higher risk of adverse events.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

ITPRIPL1 binds CD3ε to impede T cell activation and enable tumor immune evasion.

Cancer immunotherapy has transformed treatment possibilities, but its effectiveness differs significantly among patients, indicating the presence of alternative pathways for immune evasion. Here, we show that ITPRIPL1 functions as an inhibitory ligand of CD3ε, and its expression inhibits T cells in the tumor microenvironment. The binding of ITPRIPL1 extracellular domain to CD3ε on T cells significantly decreased calcium influx and ZAP70 phosphorylation, impeding initial T cell activation. Treatment with a neutralizing antibody against ITPRIPL1 restrained tumor growth and promoted T cell infiltration in mouse models across various solid tumor types. The antibody targeting canine ITPRIPL1 exhibited notable therapeutic efficacy against naturally occurring tumors in pet clinics. These findings highlight the role of ITPRIPL1 (or CD3L1, CD3ε ligand 1) in impeding T cell activation during the critical "signal one" phase. This discovery positions ITPRIPL1 as a promising therapeutic target against multiple tumor types.

Role of SYVN1 in the control of airway remodeling in asthma protection by promoting SIRT2 ubiquitination and degradation.

BACKGROUND: Asthma is a heterogenous disease that characterized by airway remodeling. SYVN1 (Synoviolin 1) acts as an E3 ligase to mediate the suppression of endoplasmic reticulum (ER) stress through ubiquitination and degradation. However, the role of SYVN1 in the pathogenesis of asthma is unclear. RESULTS: In the present study, an ovalbumin (OVA)-induced murine model was used to evaluate the effect of SYVN1 on asthma. An increase in SYVN1 expression was observed in the lungs of mice after OVA induction. Overexpression of SYVN1 attenuated airway inflammation, goblet cell hyperplasia and collagen deposition induced by OVA. The increased ER stress-related proteins and altered epithelial-mesenchymal transition (EMT) markers were also inhibited by SYVN1 in vivo. Next, TGF-ß1-induced bronchial epithelial cells (BEAS-2B) were used to induce EMT process in vitro. Results showed that TGF-ß1 stimulation downregulated the expression of SYVN1, and SYVN1 overexpression prevented ER stress response and EMT process in TGF-ß1-induced cells. In addition, we identified that SYVN1 bound to SIRT2 and promoted its ubiquitination and degradation. SIRT2 overexpression abrogated the protection of SYVN1 on ER stress and EMT in vitro. CONCLUSIONS: These data suggest that SYVN1 suppresses ER stress through the ubiquitination and degradation of SIRT2 to block EMT process, thereby protecting against airway remodeling in asthma.

Internet accessibility and incident depressive symptoms in middle aged and older adults in China: A national longitudinal cohort study.

BACKGROUND: With the rapid development of the Internet over the past ten years, its widespread applications and accessibility may cause dynamic changes in the association between internet use and depressive symptoms. OBJECTIVE: We aim to explore the association between internet accessibility (including broadband connection, internet use, frequency, and devices for internet use), as well as its changes, and the risk of incident depressive symptoms for middle aged and older adults based on a cohort study. METHODS: 8772 participants with three repeat waves of follow-up (average 6.04 years) were included. Cox proportional hazards regressions were used to explore risk effects. Hazard ratios (HRs) and 95 % Confidence Intervals [CI] were presented. RESULTS: Incidence density for depressive symptoms was 53.89 for every 1000 person-years. The rate of internet usage by middle aged and older adults in China increased evidently from 2012 to 2018 (16.39 % vs 77.41 %). Broadband internet connection (BIC) (HR = 0.80, 95%CI: 0.71, 0.90) and moderate frequency of internet use (IU) (HR = 0.30, 95%CI: 0.10, 0.92) were associated with decreased risk of depressive symptoms. Participants who changed from no internet accessibility to internet accessibility were associated with a lower risk of depressive symptoms (BIC: HR = 0.46, 95%CI: 0.41, 0.51; IU: HR = 0.42, 95%CI: 0.34, 0.51). Using large screen devices (HR = 0.64, 95%CI: 0.45, 0.91) for internet access, instead of phones, was associated with lower risk of depressive symptoms. CONCLUSIONS: Older adults should be encouraged to use the Internet; online time, frequency, and devices for internet use should be considered simultaneously.

Dietary patterns, uric acid levels, and hyperuricemia: a systematic review and meta-analysis.

Background: Studies investigating the effects of dietary intake on serum uric acid (SUA) and hyperuricemia have yielded inconsistent results. Therefore, we conducted a meta-analysis to assess the associations between various dietary patterns and SUA levels as well as hyperuricemia. Methods: We searched PubMed, Web of Science, and EMBASE databases for relevant articles examining the association between dietary intake and SUA levels and/or hyperuricemia published until March 2023. Dietary intake patterns were classified into plant-based, animal-based, and mixed dietary patterns based on predominant foods. The pooled effect sizes of eligible studies and their corresponding 95% confidence intervals (CIs) were estimated using random-effects models. Publication bias was assessed using Egger's test. Results: We included 41 studies, comprising 359 317 participants, that investigated the effects of dietary patterns on SUA levels (n = 25) and hyperuricemia (n = 19). Our findings suggested that a plant-based dietary pattern was associated with decreased SUA levels in both interventional (standard mean difference: -0.24 mg dL-1, 95% CI: -0.42, -0.06; I2 = 61.4%) and observational studies (odds ratio (OR): 0.92, 95% CI: 0.89, 0.95, I2 = 91.1%); this association was stronger in men (OR: 0.45, 95% CI: 0.35, 0.58; I2 = 0). We observed that plant- and animal-based dietary patterns were associated with a reduced risk (OR: 0.75; 95% CI: 0.67, 0.83, I2 = 93.3%) and an increased risk (OR: 1.38; 95% CI: 1.20, 1.59, I2 = 88.4%) of hyperuricemia, respectively. Conclusions: Collectively, a plant-based dietary pattern is negatively associated with SUA levels and hyperuricemia. Therefore, a plant-based dietary pattern should be recommended for the management of SUA levels and the prevention of hyperuricemia.

Dietary intake patterns during pregnancy and excessive gestational weight gain: a systematic review and meta-analysis.

Excessive gestational weight gain (EGWG) is associated with gestational complications and adverse birth outcomes. Dietary intake is closely related to EGWG; however, evidence of the association between different dietary patterns and EGWG is inconsistent. We conducted a meta-analysis to systematically evaluate this association using articles from PubMed, Embase, and Web of Science databases published up to March 1st 2023 and included observational studies revealing an association between EGWG and dietary patterns during pregnancy. Dietary patterns were categorized into three groups: healthy, unhealthy, and mixed. Summary odds ratio (OR) and 95% confidence interval (CI) were calculated using the fixed-effects (I2 < 50%) or random-effects model (I2 ≥ 50%). Fourteen studies from eleven countries, including a total of 77,550 participants, met the inclusion criteria. The overall effect of healthy dietary patterns on EGWG was non-significant. After excluding one result in overweight participants, a significant negative association between healthy dietary patterns and EGWG was found in studies with a priori defined healthy dietary patterns (OR = 0.97, 95% CI: 0.94-1.00, P = 0.047), with sample size <1000 (OR = 0.68, 95% CI: 0.48-0.97, P = 0.031), and cohort studies (OR = 0.97, 95% CI: 0.95-1.00, P = 0.043). Overall analysis revealed a significant association between unhealthy dietary patterns and EGWG (OR = 1.22, 95% CI: 1.02-1.45, P = 0.031), and the results were similar in sub-groups of cohort studies (OR = 1.23, 95% CI: 1.02-1.49, P = 0.009) and those with a sample size < 1000 (OR = 1.31, 95% CI: 1.07-1.61, P = 0.03). A healthy dietary pattern instead of an unhealthy dietary pattern is recommended for pregnant women to prevent EGWG. This meta-analysis was registered in PROSPERO as CRD42023404179.

Human bone marrow-mesenchymal stem cell-derived exosomal microRNA-188 reduces bronchial smooth muscle cell proliferation in asthma through suppressing the JARID2/Wnt/ß-catenin axis.

The functions of exosomes in allergic diseases including asthma have aroused increasing concerns. This paper focuses on the effects of exosomes derived from human bone marrow-mesenchymal stem cells (hBM-MSCs) on the proliferation of bronchial smooth muscle cells in asthma and the mechanism involved. Exosomes were extracted from hBM-MSCs and identified. Human BSMCs were induced with transforming growth factor (TGF)-ß1 to mimic an asthma-like condition in vitro and then treated with exosomes. A mouse model with asthma was induced by ovalbumin (OVA) and treated with exosomes for in vivo study. The hBM-MSC-derived exosomes significantly reduced the abnormal proliferation and migration of TGF-ß1-treated BSMCs. microRNA (miR)-188 was the most enriched miRNA in exosomes according the microarray analysis, and JARID2 was identified as a mRNA target of miR-188. Either downregulation of miR-188 or upregulation of JARID2 blocked the protective effects of exosomes on BSMCs. JARID2 activated the Wnt/ß-catenin signaling pathway. In the asthmatic mice, hBM-MSC-derived exosomes reduced inflammatory cell infiltration, mucus production, and collagen deposition in mouse lung tissues. In conclusion, this study suggestes that hBM-MSC-derived exosomes suppress proliferation of BSMCs and lung injury in asthmatic mice through the miR-188/JARID2/Wnt/ß-catenin axis. This study may provide novel insights into asthma management.

Bidirectional Association Between Asthma and Obesity During Childhood and Adolescence: A Systematic Review and Meta-Analysis.

Objective: Co-occurrence of pediatric asthma and obesity has been widely reported, yet the causal directions between these two disorders are still not well-understood. The objective of this meta-analysis is to explore whether there is a possibility of a bidirectional association for these two disorders in children and adolescents. Methods: PubMed, Embase, Web of Science, and CENTRAL databases were searched up to August 2020. Cohort studies reporting the associations of obesity with risk of physician-diagnosed asthma or physician-diagnosed asthma with risk of obesity in children and adolescents were eligible for the review. Results: A total of 3,091 records were identified from the four databases, with final inclusion of nine. Six studies reported the association between obesity and risk of asthma; three studies reported the association between asthma and risk of childhood obesity. As evaluated by the Newcastle-Ottawa quality assessment scale, all studies were assessed as high-quality studies. There was a statistically significant association between obesity and increased risk of physician-diagnosed asthma in children and adolescents. The pooled RR was 1.39 (95% CI: 1.28, 1.50; p < 0.001), with significant heterogeneity across studies (I 2 = 81.7%; p heterogeneity < 0.001). The pooled RR in boys was 1.53 (95% CI: 1.17, 1.99; p = 0.002), but such a significant association was not observed in girls (RR = 1.17, 95% CI: 0.79, 1.72; p = 0.434). For the association of asthma with risk of childhood obesity, the pooled RR was 1.47 (95%CI: 1.25, 1.72; p < 0.001) without statistical heterogeneity (I 2 = 0%, p heterogeneity = 0.652). Conclusion: There is a bidirectional association between obesity and asthma during childhood and adolescence, suggesting that childhood obesity drives an increase in the onset of asthma; meanwhile, childhood asthma may also increase risk of obesity for children and adolescents.

Effects of Single-Nucleotide Polymorphisms in the TLR7 and TLR9 Genes of Asthmatic Children.

BACKGROUND: To reveal the status of TLR7 and TLR9 SNPs among children and identify correlations between TLR7/TLR9 and asthma susceptibility and phenotypes. METHOD: Genomes were isolated from the blood samples of 100 asthmatic and 104 healthy children. To determine the status of TLR7 (rsl79009 and rs5935436) and TLR9 (rsl87084 and rs5743836) SNPs, DNA was amplified by PCR and subjected to Sanger sequencing. T and C polymorphisms at nucleotide position -1486 (TLR9 rsl87084) was discovered in both groups. RESULTS: The frequencies of TT, TC, and CC genotypes at position -1486 were significantly different when the research group was compared to the control group. There were also statistically significant differences in the genotypes at position -1486 based on age and gender following stratification analysis (p<0.05). The rsl79009 (T→C) polymorphism of TLR7 was observed in both groups. There was a statistically significant difference in the genotype frequencies at locus rsl79009 between the two groups (p<0.05). In addition, there were statistically significant differences in the genotype frequencies at locus rsl79009 based on age and gender following stratification analysis (p<0.05). CONCLUSION: Significant correlations between TLR9/TLR7 SNPs and pediatric asthma were identified. The genotypes at TLR7 rsl79009 and TLR9 rsl87084 were significantly different between the two groups.

Epigallocatechin gallate improves airway inflammation through TGF­ß1 signaling pathway in asthmatic mice.

The present study aimed to investigate the effect of epigallocatechin gallate (EGCG) on airway inflammation in mice with bronchial asthma, and the regulatory mechanism of transforming growth factor (TGF)­ß1 signaling pathway, so as to provide theoretical basis for research and development of a novel drug for clinical treatment. Mouse models of bronchial asthma were established and injected with dexamethasone and EGCG via the caudal vein. 7 days later, bronchoalveolar tissue was collected for hematoxylin and eosin staining. Determination of airway resistance (AWR) and lung function in mice was detected. Serum was separated for cytometric bead array to detect the changes in inflammatory factors. Bronchoalveolar lavage fluid was collected for eosinophil and neutrophil counts. Fresh blood was obtained for flow cytometry to determine the percentages of Th17 and Treg cells. Bronchovesicular tissue was utilized for western blot assay and reverse transcription­quantitative polymerase chain reaction to determine the proteins and transcription factors in the TGF­ß1 pathway. EGCG 20 mg/kg significantly reduced asthmatic symptoms, lung inflammatory cell infiltration, and the inflammatory factor levels of interleukin (IL)­2, IL­6 and tumor necrosis factor (TNF)­α. In addition, it increased the levels of inflammatory factors, including IL­10, diminished the percentage of Th17 cells, increased the percentage of Treg cells, and decreased the expression of TGF­ß1 and phosphorylated (p)­Smad2/3 expression. Following the inhibition of the TGF­ß1 receptor, the anti­inflammatory effect of EGCG disappeared, and the expression of TGF­ß1 and p­Smad2/3 increased. EGCG attenuated airway inflammation in asthmatic mice, decreased the percentage of Th17 cells and increased the percentage of Treg cells. The anti­inflammatory effect of EGCG is achieved via the TGF­ß1 signaling pathway.

Expression of vitamin D receptor in bronchial asthma and its bioinformatics prediction.

Vitamin D receptors (VDRs) are associated with the occurrence and development of asthma. The aim of the present study was to analyze the secondary structure and B­cell and T­cell epitopes of VDR using online prediction software and aid in the future development of a highly efficient epitope­based vaccine against asthma. Blood samples were collected from peripheral blood of asthmatic children. Reverse transcription quantitative­polymerase chain reaction (RT­qPCR) was performed to detect the expression of VDR in the peripheral blood. Mouse models of asthma were established. Hematoxylin and eosin staining was performed to observe the pathological alterations of the lungs of mice. Immunohistochemistry, western blot analysis and RT­qPCR were performed to detect the expression of VDR in the lungs of asthmatic mice. Online prediction software immune epitope database and analysis resource, SYFPEITHI and linear epitope prediction based on propensity scale and support vector machines were used to predict the B­cell and T­cell epitopes and the RasMol and 3DLigandSite were used to analyze the tertiary structure of VDR. RT­qPCR demonstrated that VDR expression in the peripheral blood of asthmatic children was decreased. Immunohistochemistry, western blotting and RT­qPCR demonstrated that VDR expression also decreased in the lungs of mouse models of asthma. VDR B­cell epitopes were identified at 37­45, 88­94, 123­131, 231­239, 286­294 and 342­350 positions of the amino acid sequence and VDR T­cell epitopes were identified at 125­130, 231­239 and 265­272 positions. A total of six B­cell epitopes and three T­cell epitopes for VDR were predicted by bioinformatics, which when validated, may in the future aid in immunological diagnosis and development of a targeted drug therapy for clinical asthma.