Plasma-derived exosomal hsa-miR-184 and hsa-mir-6766-3p as promising diagnostic biomarkers for early detection of children's cardiac surgery-associated acute kidney injury.

There is little known about the contribution of exosomal microRNAs (exomiRs) in the children's cardiac surgery-associated acute kidney injury (CSA-AKI). This study aimed to find diagnostic biomarkers for predicting CSA-AKI in children. A prospective observational study was conducted from April 2020 to March 2021.According to the changes of serum creatinine (SCr) value and urine volume within 48 h, the children were divided into acute kidney injury (AKI) group and non-AKI group. Serum samples were collected 4 h after cardiac surgery. Isolation of extracellular vesicles (EVs) and extraction of exomiRs from serum samples. Illumina high-throughput sequencing was used to quantify exomiRs and screen candidate microRNAs (miRNAs). Expression levels of candidate miRNAs were validated using droplet digital polymerase chain reaction (ddPCR). Normal and injuried rats' kidney tissue were collected for tissue validation. In the pre-experimental stage (4 AKI vs. 4 non-AKI), hsa-miR-184, hsa-miR-4800-3p, hsa-miR-203a-3p and hsa-miR-6766-3p were selected as candidate genes. In the verification stage (8 AKI vs. 12 non-AKI), the expression of hsa-miR-184 in AKI group was significantly lower than that in non-AKI group (P = 0.031), and the expression of hsa-miR-4800-3p and hsa-miR-6766-3p in AKI group was significantly higher than that in non-AKI group (P = 0.01 and P = 0.047). There was no significant difference in the expression of hsa-miR-203a-3p between the two groups (P > 0.05). The expression of rats' kidney tissue rno-miR-184 in AKI group was significantly lower than that in the normal group (P = 0.044). The area under the curve (AUC) of AKI predicted by hsa-miR-184 is 0.7865 and the AUC of hsa-miR-6766-3p is 0.7708. Combined with two kinds of miRNAs, the area under the curve of AKI is predicted to be 0.8646. The change of exomiRs level in circulatory system occurred in the early stage after cardiac operation, and the changes of hsa-miR-184 and hsa-miR-6766-3p content in circulatory system could predict CSA-AKI well.

The effect of lead exposure during early stage of life on expression of metabotropic glutamate receptor subtype 5 / 临床儿科杂志

Objective The effect of lead exposure on children is consistently associated with intellectual and other neurologic deficits.However the exact mechanism by which Pb~(2+) exerts toxic effects on developmental central nervous system remains unknown.Our group has found by gene-chip test that the expression of metabotropic glutamate receptor subtype 5 (mGluR5) mRNA was changed by lead exposure.The present study aimed to examine the effects of different level of lead exposure on the expression of mCluR5 in gestation and lactation.Methods Sprague-Dawley rats were exposed to lead acetate during gestation and lactation.Three concentrations of 0.05%,0.2%,and 0.5% lead acetate were applied and considered as low,middle and high exposure group respectively.The Pb levels of blood and hippocampus of pups were analyzed at weaning to evaluate the actual lead content at the end of the exposure.The impact of lead exposure on the expression of mGluR5 mRNA and protein in hippocampal tissue of pups was investigated by quantitative real-time polymerase chain reaction (PCR) and Western blot.The potential role of the expression of mGluR5 mRNA and protein in lead neurotoxicity were discussed.Results The levels of lead in blood and hippocampus from lead-exposed rats were significantly higher than those in the controls and positively related to the degree of lead exposure.The results of real-time PCR and Western blot showed that exposure to lead acetate decreased the expression of mCluR5 mRNA and protein with a dose-dependent manner.Conclusions Hippocampal mGluR5 might be involved in lead-induced neurotoxicity.