Ammonia induces autophagy via circ-IFNLR1/miR-2188-5p/RNF182 axis in tracheas of chickens.

Ammonia (NH3 ), an air pollutant in the living environment, has many toxic effects on various tissues and organs. However, the underlying mechanisms of NH3 -induced tracheal cell autophagy remains poorly understood. In present study, chickens and LMH cells were used as NH3 exposure models to investigate toxic effects. The change of tracheal tissues ultrastructure showed that NH3 exposure induced autolysosomes. The differential expression of 12 circularRNAs (circRNAs) was induced by NH3 exposure using circRNAs transcriptome analysis in broiler tracheas. We further found that circ-IFNLR1 was down-regulated, and miR-2188-5p was up-regulated in tracheal tissues under NH3 exposure. Bioinformatics analysis and dual luciferase reporter system showed that circ-IFNLR1 bound directly to miR-2188-5p and regulated each other, and miR-2188-5p regulated RNF182. Overexpression of miR-2188-5p caused autophagy and its inhibition partially reversed autophagy in LMH cells which were caused by ammonia stimulation or knockdown of circ-IFNLR1. The expressions of three autophagy-related genes (LC3, Beclin 1, and BNIP3) were observably up-regulated. Our results indicated that NH3 exposure caused autophagy through circ-IFNLR1/miR-2188-5p/RNF182. These results provided new insights for the study of ammonia on environmental toxicology on ceRNA and circRNAs in vivo and vitro.

[Clinical observation of the curative effect of Qiangxin Mixture on congestive heart failure].

OBJECTIVE: To investigate the efficacy of Qiangxin Mixture in patients with congestive heart failure (CHF). METHODS: Sixty cases of CHF were randomly divided into Qiangxin Mixture group (treatment group, n=30) and digoxin group (control group, n=30). The total clinical effective rate, integra of the symptoms of kidney deficiency, classification of functional capacity of the New York Heart Association (NYHA), and echocardiogram [ejection fraction (EF), cardiac output (CO), interventricular septal thickness (IVST), posterior wall thickness (PWT), left ventricular mass index (LVMI)] as well as the measurement of plasma endothelin, angiotensin II and atrial natriuretic peptide were observed in both groups. RESULTS: The total clinical effective rate of Qiangxin Mixture group was 87%, and improvement was significantly observed in the Lee CHF score, classification of functional capacity of the NYHA, EF and CO (P<0.05, vs before treatment), but no significant improvement in digoxin group (P>0.05). The integra of the symptoms of kidney deficiency, the levels of plasma ET, Ang II and ANP decreased significantly (P<0.01, vs before treatment and digoxin group respectively). IVST, PWT and LVMI were also reduced significantly (P<0.01, vs before treatment; P<0.05 vs digoxin group). CONCLUSION: The Qiangxin Mixture is effective in enhancing cardiac contraction, improving hemodynamics in the short-term and rectifying some indexes in the long-term, so it could postpone the processes of CHF. This mechanism may be related to decreasing the stimulating factors (angiotensin, endothelin) which trigger the cardiac remodeling, delaying or reversing the cardiac remodeling.