Transcriptomics reveals apigenin alleviates airway inflammation and epithelial cell apoptosis in allergic asthma via MAPK pathway.

Persistent chronic inflammation of the lungs and airway remodeling are important pathological features that cannot be ignored in patients with chronic asthma. Apigenin (API) is a natural small molecule compound with good anti-inflammatory and antioxidant activity that has been widely reported in recent years, but its role in chronic asthma is not well defined. Our study began with oral gavage intervention using API (10, 20 mg/kg) or dexamethasone (DEX, 2 mg/kg) in a BALB/c mouse model of ovalbumin (OVA) sensitization. Different doses of API intervention effectively reduced airway resistance in the administered group. Additionally, inflammation was downregulated, mucus secretion was reduced, and airway remodeling was inhibited in the API intervention group compared with the model group. Asthma-related inflammatory cytokines, such as IgE, IL-4, IL-5, IL-13, and IL-17, were downregulated in alveolar lavage fluid. Moreover, the apoptosis level of the administered group was found to be lower than that of the model group in the Tunel staining experiment. By analyzing transcriptome sequencing results, we found that API may exert anti-inflammatory and anti-apoptotic effects by inhibiting the MAPK pathway. Our subsequent results supported this conclusion, showing that the phosphorylation levels of ERKs, JNKs, and p38 MAPKs were inhibited in the administered group relative to the model group. Downstream expression of the apoptosis-related protein B-cell lymphoma-2 (Bcl-2) was upregulated, and the expression of Bcl-2-associated × protein (Bax) and cleaved caspase-3 was downregulated. To further investigate the specific mechanism by which API acted, we established an in vitro model with house dust mite (HDM) stimulation, using API (10, 20 µM) for administration intervention. The results showed that API was able to improve cell viability, inhibit ROS production, and reverse HDM-induced decreases in mitochondrial membrane potential (MMP) and apoptosis in airway epithelial cells via the MAPK pathway.

A novel iridoid glycoside leonuride (ajugol) attenuates airway inflammation and remodeling through inhibiting type-2 high cytokine/chemokine activity in OVA-induced asthmatic mice.

BACKGROUND: Asthma is a chronic airway disorder with a hallmark feature of airflow obstruction that associated with the remodeling and inflammation in the airway wall. Effective therapy for controlling both remodeling and inflammation is still urgently needed. Leonuride is the main pharmacological component identified from Bu-Shen-Yi-Qi-Tang (BSYQT) which has been traditionally used in treatment of lung diseases. However, no pharmacological effects of leonuride in asthma were reported. PURPOSE: Here we aimed to investigated whether leonuride provided a therapeutic efficacy in reversing asthma airway remodeling and inflammation and uncover the underlying mechanisms. STUDY DESIGN AND METHODS: Mouse models of chronic asthma were developed with ovalbumin (OVA) exposure for 8 weeks. Respiratory mechanics, lung histopathology and asthma-related cytokines were examined. Lung tissues were analyzed using RNA sequencing to reveal the transcriptional profiling changes. RESULTS: After oral administration with leonuride (15 mg/kg or 30 mg/kg), mice exhibited a lower airway hyperresponsiveness in comparison to asthmatic mice. Leonuride suppressed airway inflammation evidenced by the significant reductions in accumulation of inflammatory cells around bronchi and vessels, leukocyte population counts and the abundance of type 2 inflammatory mediators (OVA specific IgE, IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF). On the other hand, leonuride slowed down the process of active remodeling as demonstrated by weaker goblet cell metaplasia and subepithelial fibrosis in lung histopathology and lower transforming growth factor (TGF)-ß1 levels in serum and BALF in comparison to mice treated with OVA only. Furthermore, we uncovered transcriptional profiling alternations in lung tissue of mice after OVA exposure and leonuride treatment. Gene sets belonging to type-2 cytokine/chemokine activity stood out in leonuride target transcripts. Those upregulated (Bmp10, Ccl12, Ccl22, Ccl8, Ccl9, Cxcl15, Il13, Il33, Tnfrsf9, Il31ra, Il5ra, Il13ra2 and Ccl24) or downregulated (Acvr1c and Il18) genes in asthmatic mice, were all reversely regulated by leonuride treatment. CONCLUSIONS: Our results revealed the therapeutic efficacy of leonuride in experimental chronic asthma for the first time, and implied that its anti-inflammatory and antifibrotic properties might be mediated by regulation of type-2 high cytokine/chemokines responses.

Prevalence of adenovirus in children with acute respiratory tract infection in Lanzhou, China.

BACKGROUND: Human adenovirus (HAdV) is an important agent causing respiratory tract infection in children. Information on the epidemiological and clinical features of HAdV is limited in children with acute respiratory tract infections (ARTIs) in China, especially those of a novel genotype, Ad55. METHODS: In total, 1169 nasopharyngeal aspirates were collected from children younger than 14 years with ARTIs between November 2006 and November 2009. The polymerase chain reaction (PCR) was used to screen HAdVs. All PCR-positive products were sequenced. RESULTS: 74 of 1169 (6.33%) specimens were positive for HAdVs. Among positive cases, AdV3 (58/74) was detected most frequently, followed by AdV11 (10/74), AdV2 (2/74), AdV7 (2/69), AdV6 (1/74), and AdV1 (1/74). AdV55 was found in one case. The incidence of HAdV infection peaked in children aged 3-7 years. The most common clinical diagnosis was upper respiratory infection, and the most common syndrome was fever and cough.The comparison of HAdV and RSV group revealed that Children infected with group AdV were significant older than children infected with group RSV, had more fever but less frequently wheezing, and cough, crackles, and cyanosis, The duration of hospitalization between the AdV group and RSV group was not significant, but a greater frequency of LRTIs was observed in RSV group. CONCLUSIONS: HAdV is an important viral agent in children with ARTIs in Lanzhou City, China. Multiple HAdV serotypes co-circulated with Ad3, which was predominant in this 3-year study. The novel AdV55 genotype was found in one case. No fixed seasonal rhythm could be identified.

Human respiratory syncytial virus in children with acute respiratory tract infections in China.

There are limited data on the prevalence and clinical and molecular characterization of human respiratory syncytial virus (HRSV) in children with acute respiratory tract infections (ARTIs) in China. From December 2006 to March 2009, 894 nasopharyngeal aspirates (NPAs) were collected from children under 14 years of age with ARTIs. Samples were screened for HRSV and genotyped by reverse transcription-PCR (RT-PCR) and sequencing. Demographic and clinical information was recorded. A total of 38.14% (341/894) of samples were positive for HRSV. Phylogenetic analysis revealed that 60.4% of the selected 227 RSV strains were GA2, 34.4% were BA, 4.8% were GB2, and 0.4% were GB3. A total of 40.47% of all of the RSV-positive samples were coinfected with other respiratory viruses, and adenovirus was the most common additional respiratory virus. No statistical differences were found in the frequency of diagnosis and symptoms between the coinfection group and monoinfection group. Additionally, no statistical differences were found in epidemiological characterizations or disease severity between genotype BA- and GA2-positive patients, except for a greater frequency of lower respiratory tract infections (LRTIs) (mostly bronchitis)with BA. HRSV is the most important viral pathogen in Chinese children with ARTIs. Four genotypes (i.e., GA2, BA, GB2, and GB3) circulate locally, and the predominant genotype may shift between seasons. Coinfection with other viruses does not affect disease severity. HRSV genotypes were not associated with different epidemiological characterizations or disease severity.

Prevalence and clinical characterization of a newly identified human rhinovirus C species in children with acute respiratory tract infections.

Human rhinovirus C (HRV-C) is a newly identified genotype of HRV found in patients with respiratory tract infections (RTIs); however, its epidemiological profile and clinical characteristics are not well understood. In this study, Chinese children with RTIs were screened for HRV-C and their epidemiological and clinical characteristics were analyzed. From December 2006 to November 2007, 406 nasopharyngeal aspirates from children younger than 14 years of age with RTIs were screened for HRV and other common respiratory viruses by PCR or reverse transcription-PCR. Two-hundred twenty-four (55.2%) of the specimens were infected with at least one virus, including 53 patients with HRV (13%). HRV-A, HRV-B, and HRV-C were detected in 22, 12, and 19 specimens, respectively. HRV-C was detected mainly from December 2006 to April 2007 and from October to November 2007, with peaks in December and April (10/19). Acute upper respiratory infection and bronchopneumonia were observed in 53 and 37% of the cases, respectively. The most common symptoms were cough (82%), runny nose (53%), and fever (37%). Wheezing and bronchiolitis were less common in patients infected with HRV-C than in those infected with respiratory syncytial virus (RSV). Partial sequencing of the genes coding for VP4 and VP2 revealed that the HRV-C strains were 56 to 62% identical at the amino acid level to HRV-B and HRV-A reference strains and 80 to 99% identical to HRV-C reference strains. In conclusion, HRV-C is an important cause of RTIs in children, and highly diversified strains of HRV-C are prevalent in China. HRV-C may produce different epidemiological features, and patients infected with HRV-C may exhibit different clinical features from patients infected with RSV or HRV-A/B.

Prevalence of human KI and WU polyomaviruses in children with acute respiratory tract infection in China.

The KI and WU polyomaviruses were found in 11 (2.7%) and 17 (4.2%) of 406 nasopharyngeal aspirates, respectively, from children with acute respiratory tract infection (ARTI). The phylogenetic analysis indicates that they are all in the same cluster as the prototype strains. Our findings suggest that they are common in children with ARTI in China.

[WU polyomavirus and KI polyomavirus detected in specimens from children with acute respiratory tract infection in China].

OBJECTIVE: To investigate newly identified polyomavirus WUV and WUV and KIPyV are associated with acute respiratory infections in China, tests were developed to detect WUV and KIPyV gene fragments from nasopharyngeal aspirates collected from children with ARI fron Nov. 2006 to Oct. 2007. METHODS: A total of 318 clinical samples were tested for WUV and KIPyV using PCR method. The positive products were sequenced and compared with those in GenBank. RESULTS: 14 of the 318 Samples were positive (WUV was 2.2%, KIPyV was 2.2%). All of children who were positive for WUV or KIPyV had respiratory illness. CONCLUSION: Polyomavirus WU and KIPyV infection may be associated with upper and lower respiratory diseases.