Airway remodeling is characterized by airway wall thickening, subepithelial fibrosis, increased smooth muscle mass, angiogenesis and increased mucous glands, which can lead to a chronic and obstinate asthma with pulmonary function depression. In the present study, we investigated whether the astragalus extract inhibits airway remodeling in a mouse asthma model and observed the effects of astragalus extract on the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway in ovalbumin-sensitized mice. Mice were sensitized and challenged by ovalbumin to establish a model of asthma. Treatments included the astragalus extract and budesonide. Lung tissues were obtained for hematoxylin and eosin staining and Periodic acid-Schiff staining after the final ovalbumin challenge. Levels of TGF-β1 were assessed by immunohistology and ELISA, levels of TGF-β1 mRNA were measured by RT-PCR, and levels of P-Smad2/3 and T-Smad2/3 were assessed by western blotting. Astragalus extract and budesonide reduced allergen-induced increases in the thickness of bronchial airway and mucous gland hypertrophy, goblet cell hyperplasia and collagen deposition. Levels of lung TGF-β1, TGF-β1 mRNA and P-Smad2/3 were significantly reduced in mice treated with astragalus extract and budesonide. Astragalus extract improved asthma airway remodeling by inhibiting the expression of the TGF-β1/Smad signaling pathway, and may be a potential drug for the treatment of patients with a severe asthma airway.

Background: MED13L-related intellectual disability is a new syndrome that is characterized by intellectual disability (ID), motor developmental delay, speech impairment, hypotonia and facial dysmorphism. Both the MED13L haploinsufficiency mutation and missense mutation were reported to be causative. It has also been reported that patients carrying missense mutations have more frequent epilepsy and show a more severe phenotype. Case presentation: We report a child with ID, speech impairment, severe motor developmental delay, facial deformity, hypotonia, muscular atrophy, scoliosis, odontoprisis, abnormal electroencephalogram (EEG), and congenital ureteropelvic junction obstruction (UPJO) combined with high ureter attachment. We used whole-exome sequencing (WES) to detect the genetic aberration of the child and found a de novo mutation, c.2605C > T (p.Pro869Ser), in the MED13L gene. Neither of her parents carried the mutation. Additionally, we review the literature and summarize the phenotypes and features of reported missense mutations. After reviewing the literature, approximately 17 missense mutations in 20 patients have been reported thus far. For 18 patients (including our case) whose clinical manifestations were provided, 100% of the patients had ID or developmental delay (DD). A total of 88.9, 83.3 and 66.7% of the patients had speech impairment, delayed milestones and hypotonia, respectively. A total of 83.3% of the patients exhibited craniofacial deformity or other dysmorphic features. Behavioral difficulties and autistic features were observed in 55.6% of the patients. Cardiac anomalies were seen in only 27.8% of the patients. Of these patients, 44.4% had epileptic seizures. Of the 17 mutations, 2 were located in the N-terminal domain, 8 were located in the C-terminal domain, and 1 was located in an α-helical sequence stretch. One of them was located in the MID domain of the MedPIWI module. Conclusions: We report a new patient with a reported missense mutation, c.2605C > T (p.Pro869Ser), who exhibited some infrequent manifestations except common phenotypes, which may broaden the known clinical spectrum. Additionally, by reviewing the literature, we also found that patients with missense mutations have a higher incidence of seizures, MRI abnormalities, autistic features and cardiac anomalies. They also have more severe ID and hypotonia. Our case further demonstrates that Pro869Ser is a hotspot mutation of the MED13L gene.