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Although many efforts have been made to improve management strategies and diagnostic methods in the past several decades, the prevention of anastomotic complications, such as anastomotic leaks and strictures, remain a major clinical challenge. Therefore, new molecular pathways need to be identified that regulate anastomotic healing, and to design new treatments for patients after anastomosis to reduce the occurrence of complications. Rabbits were treated with a MST1/2 inhibitor XMU-XP-1, a Chinese medicine formula Shenhuang plaster (SHP) or a control vehicle immediately after surgery. The anastomotic burst pressure, collagen deposition, and hydroxyproline concentration were evaluated at 3 and 7 days after the surgery, and qRT-PCR and western-blot analyses were used to characterize mRNA and protein expression levels. Both XMU-XP-1 and SHP significantly increased anastomotic burst pressure, collagen deposition, and the concentration of hydroxyproline in intestinal anastomotic tissue at postoperative day 7 (POD 7). Importantly, SHP could induce TGF-p1 expression, which activated its downstream target Smad-2 to activate the TGF-p1 signaling pathway. Moreover, SHP reduced the phosphorylation level of YAP and increased its active form, and treatment with verteporfin, a YAP-TEAD complex inhibitor, significantly suppressed the effects induced by SHP during anastomotic tissue healing. This study demonstrated that activation of the Hippo-YAP pathway enhances anastomotic healing, and that SHP enhances both the TGF-p1/Smad and YAP signaling pathways to promote rabbit anastomotic healing after surgery. These results suggest that SHP could be used to treat patients who underwent anastomosis to prevent the occurrence of anastomotic complications. [ABSTRACT FROM AUTHOR]

Background. Asthma is a chronic inflammatory disease of respiratory with serious risks for children. This study explored myeloid-derived suppressor cells (MDSCs) on the pathogenesis of asthmatic children and mice. Methods. The clinical study enrolled 30 asthma, 20 pneumonia, and 20 control participants. The MDSCs, Th17 and Th1 cells percentage, and IL-4, IL-12, IL-10, and IFN-γ levels were detected by flow cytometry and ELISA. In experimental asthma, mice were divided into control, ovalbumin (OVA), and OVA + MDSCs groups. The changes in inflammatory cell count and the levels of IL-5, IL-12, and IL-10 in mice BALF and the levels of inflammatory factors, IgE, and IFN-γ in mice were detected by ELISA. The amount of ROS generation and pathological changes and the levels of caspase 1 and caspase 3 were tested by flow cytometry, HE and PAS staining, and immunohistochemistry. The expression of cleaved caspase 1/caspase 1 and cleaved caspase 3/caspase 3 was detected by western blot. Results. In clinical trials, the levels of IL-12, IFN-γ, and Th1 percentage decreased in pneumonia and asthma children's peripheral blood, while the levels of IL-4 and IL-10 and the percentages MDSCs and Th17 increased. In asthma mice, pathological staining showed that asthma caused lung inflammation and damage, while the OVA + MDSC group was severer. Moreover, the percentages of eosinophils, neutrophils, lymphocytes, and the levels of inflammatory factors, IgE, ROS production, caspase 1, caspase 3, cleaved caspase 1/caspase 1, and cleaved caspase 3/caspase 3 increased in OVA + MDSC group, while the percentage of macrophages, IL-12, and IFN-γ levels reduced, illustrating that MDSCs exacerbated asthma. Conclusion. Our study indicated that MDSCs could aggravate asthma by regulating the Th1/Th2/Th17 response. [ABSTRACT FROM AUTHOR]

Background. Asthma is a disease with airway hyperresponsive and airway inflammation. Platycodin D is a triterpenoid saponin extracted from Platycodon grandiflorus root, which has various pharmacological activities. The study mainly explored the effects of platycodin D3 (PD3) in airway remodeling and inflammation of asthma. Methods. The ovalbumin (OVA)-induced asthma mice were given PD3 (20 mg/kg, 40 mg/kg, and 80 mg/kg) in different groups. The asthma mice administrated with dexamethasone (DXM) were enrolled as the positive control group, and the normal control mice and asthma model mice separately received the same volume of saline. Mouse airway lung dynamic compliance (Cdyn) and total airway resistance (RL) were measured by the EMKA animal lung function analysis system. The inflammation factor levels were estimated by ELISA. Histopathological changes were tested by HE and PAS staining. The protein and phosphorylation levels of NF-κBp65, p38, ERK1/2, and JNK1/2 were detected by Western blot. Results. In asthmatic mice, PD3 enhanced the airway Cdyn and decreased RL to improve the airway hyperreactivity and alleviated the pathological injury of lung tissues. In addition, PD3 could reduce the infiltration of inflammatory cells in BALF and suppress the levels of eotaxin, IL-4, IL-5, IL-13, IFN-γ, and IgE. Furthermore, PD3 treatment inhibited the phosphorylation of NF-κBp65, p38, ERK1/2, and JNK1/2 proteins in asthma mice. Conclusion. PD3 treatment alleviated the airway remodeling and inflammation in asthmatic mice, which might be related to downregulating the phosphorylated proteins in the MAPK/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]