Let-7a Targeting TNFAPI3 Promotes Vascular Endothelial Cell Apoptosis of Pediatric Patients with Henoch-Schönlein Purpura via NF-κB Signaling Pathway.

Objective: We aimed at exploring the role of let-7a in the pathogenesis of pediatric Henoch-Schönlein purpura (HSP) and its related mechanism. Methods: Fifty-five pediatric HSP patients and 20 paired healthy controls were included. The expressions of let-7a and TNFAIP3 were detected by RT-qPCR or/and western blot. Vessel fibrinoid necrosis was evaluated in skin tissues by PTAH staining. The serum IgA level was measured by ELISA. Cells were transfected with let-7a inhibitor and/or TNFAIP3 siRNA, accompanied by pretreatment with NF-κB inhibitor PDTC or not. After being cultured in HSP serum, the changes in cell viability, cell apoptosis, apoptosis-related proteins, and NF-κB pathway-related proteins were detected by CCK8, flow cytometry, and western blot. Results: The let-7a expression level was positively correlated with the serum IgA level and severity degree of vascular fibrinoid necrosis in HSP patients. Let-7a expression was significantly increased, whereas cell viability and TNFAIP3 expression were obviously decreased 48 h after HUVECs were incubated with HSP serum. Let-7a knockdown upregulated the cell viability, whereas it reduced the apoptotic ratio, apoptosis protein expressions (Bax/Bcl2 ratio, cleaved-caspase 3), and NF-κB pathway activation (reflected by reduced P65 nuclear translocation and p-IκBα expression) in HUVECs (all p < 0.05). The changes induced by let-7a knockdown were obviously reversed by TNFAIP3 siRNA transfection (p < 0.05). Besides, PDTC treatment remarkably diminished the anti-apoptosis effect of let-7a knockdown and pro-apoptosis effect of TNFAIP3 siRNA on HUVECs induced by HSP serum. Conclusions: Let-7a knockdown significantly suppressed vascular endothelial cell apoptosis induced by HSP serum by targeting TNFAPI3 via NF-κB signaling pathway. Our findings provided a potential therapeutic target for the treatment of HSP.

A comparison of efficacy and safety of complementary and alternative therapies for children with asthma: A protocol for systematic review and meta analysis.

BACKGROUND: Bronchial Asthma is a chronic, hyperreactive inflammation of the airway that involves a variety of inflammatory cells. Due to the persistence of airway hyperresponsiveness, lung function is progressively damaged, making asthma more stubborn and difficult to heal. In recent years, the prevalence of childhood asthma is still on an increasing trend. Repeated asthma attacks not only affect children's life and learning, but also bring greater economic and mental burden to children's families, and even threaten children's lives. Traditional treatment methods such as oral western medicine, atomization therapy has obvious limitations, and the complementary and alternative therapy is an effective method to treat asthma in children. This study will evaluate the efficacy and safety of various complementary and alternative therapies for children with asthma by means of mesh meta-analysis. In order to provide the basis for clinical rational use. METHODS: Use the computer to search the self-built database until January 2021, the China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journals Database, China Biomedical Literature Database, PubMed, Cochrance Library, EMBASE, Web of Science, Clinical Trials and other electronic databases to collect RCT studies on complementary and alternative therapies for for children with asthma. We will screen the relevant literature included in the systematic review/meta analysis. At the same time, Revman 5.3 software will be used for meta-analysis, and grade will be used to grade the quality of evidence in the network meta-analysis. RESULTS: This study will compare the efficacy and safety of different complementary and alternative therapies to treat childhood asthma, and evaluate and rank different interventions. CONCLUSION: The combined use of complementary and alternative therapies for childhood asthma on the basis of conventional basic treatment can improve clinical efficacy, reduce the occurrence of adverse reactions, improve the quality of life of children, and provide strong support for the rational use of clinicians. INPLASY REGISTRATION NUMBER: INPLASY202120005.