Aim To explore whether edaravone (EDA), a novel free radical scavenger, protects H9c2 cardiac cells against doxorubicin ( DOX )-induced car-diotoxicity. Methods H9c2 cells were treated with 5μmol·L-1 DOX to establish a model of DOX cardio-toxicity. Cell viability was examined by cell counter kit ( CCK-8 ) . Changes in morphology and amount of ap-optotic cells were detected by Hoechst 33258 staining;intracellular level of reactive oxygen species ( ROS ) was measured by DCFH-DA staining and photofluorog-raphy;mitochondrial membrane potential ( MMP) was observed by rhodamine 123 ( RH123 ) staining and photoflurograph; the expression level of caspase-3 was determined by Western blot assay. Results Pretreat-ment of H9 c2 cells with 20 , 40 and 80 μmol · L-1 EDA for 60 min markedly inhibited cytotoxicity in-duced by 5 μmol · L-1 DOX, respectively, as evi-denced by an increase in cell viability. The protective effect induced by 40 μmol · L-1 EDA was maximal. Pretreatment of H9 c2 cells with 40 μmol · L-1 EDA for 30 , 60 , 90 and 120 min significantly attenuated DOX-induced cytotoxicity, respectively, having a max-imal protection at 60 min. Furthermore, pretreatment of H9 c2 cells with 40 μmol · L-1 EDA for 60 min be-fore exposure to 5 μmol · L-1 DOX for 24 h obviously reduced cardiac injuries, as evidenced by decreases in the DOX-induced intracellular ROS generation, num-ber of apoptotic cells, and expression of cleaved caspase-3, as well as loss of MMP. Conclusions EDA can protect H9 c2 cardiac cells against DOX-in-duced cardiotoxicity, this protection may be associated with inhibition of ROS production and preservation of MMP.

OBJECTIVETo explore whether strontium ranelate (Sr) promotes osteoblast lineage differentiation of rat bone mesenchymal stem cells (BMSCs) through the bone morphogenetic protein-2 (BMP-2)/Smad signaling pathway.

METHODSCultured rat BMSCs were exposed to different concentrations of Sr, noggin (an inhibitor of BMP-2) or Smad1 siRNA. The activity of alkaline phosphatase (ALP) in the exposed cells was detected by colorimetry, and the formation of mineralized nodules was observed with alizarin red staining. The expressions of phosphorylated (p) Smad1/5/8 and Runt-related transcription factor 2 (Runx2) in the cells were detected by Western blotting.

RESULTSExposure to Sr at 0.1 to 10 mmol/L for 1 h markedly increased the expression of p-Smad1/5/8 in the BMSCs, and the increment was the most obvious following 1 mmol/L Sr exposure. Preconditioning with 100 ng/ml noggin for 2 h inhibited Sr-induced up-regulation of p-Smad1/5/8 expressions. Exposure of the cells to 0.1 to 5 mmol/L Sr for 6 h significantly enhanced Runx2 expression, and the peak enhancement occurred following 1 mmol/L Sr exposure. Transfection of the BMSCs with Smad1 siRNA decreased the basal level of Smad1/5/8 protein expression, and also inhibited Sr-induced up-regulation of p-Smad1/5/8 and Runx2 expressions as well as Sr-induced enhancement of ALP activity and formation of mineralized nodules.

CONCLUSIONThe BMP-2/Smad pathway is involved in Sr-induced osteoblast differentiation of rat BMSCs.

Alkaline Phosphatase ; metabolism ; Animals ; Bone Marrow Cells ; cytology ; Bone Morphogenetic Protein 2 ; metabolism ; Cell Differentiation ; drug effects ; Cells, Cultured ; Mesenchymal Stromal Cells ; cytology ; Osteogenesis ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Smad1 Protein ; metabolism ; Strontium ; pharmacology ; Thiophenes ; pharmacology

Objective : To investigate the neurobehavioral development of young children aged 24 to 60 months in Shunde and explore the factors influencing the development of young children and provide reference for the interven- tion of neurobehavioral development delays in young children． Methods : A retrospective cohort study was used to enroll the young children who were initially screened by the Pediatric Neuropsychological Developmental Scale (Pe- diatric Heart Scale) with a score of ≤85 was included in the study．With a score of ≤85，the young children might be at risk of developmental delays，and needed to be further diagnosed by the GESELL Developmental Diagnostic Scale，the basic information of the young children and their mothers at the time of birth were investigated，as well as basic information about the young children at the time of completing the GESELL Developmental Diagnostic Scale was collected. Results : A total of 271 young children were included，196 males and 75 females．Young children had the lowest developmental quotient (DQ) in the language domain among the five domains (P＜0. 001) ．Multiple lin- ear regression models showed : compared with girls，the language domain DQ of boys decreased by 5. 321 points (P = 0. 049，95% CI : －10. 620 －－0. 021) ，and the personal-social domain DQ decreased by 4. 474 points (P = 0. 023，95% CI : －8. 316 －－0. 631) ．Compared with young children via natural vaginal delivery (NVD) ，the gross motor domain DQ of young children via caesarean section ( CS) decreased by 4. 890 points (P = 0. 008，95% CI : - 8. 499 －－1. 281 ) ，the fine motor domain DQ decreased by 3. 373 points ( P = 0. 037，95% CI : －6. 532 - - 0. 213) ，the language domain DQ decreased by 7. 621 points (P = 0. 004，95% CI : －12. 826 －－2. 416) ，per- sonal-social domain DQ decreased by 6. 232 points (P = 0. 001，95% CI : －10. 006 －－2. 457) ．The results of bi- nary logistic regression models showed，compared with young children via NVD，the risk of gross motor domain retar- dation in young children increased ( OR = 1. 763，95% CI : 1. 003－3. 100) ，the risk of fine motor domain retardation increased ( OR = 2. 217，95% CI : 1. 235－3. 980) ，the risk of language domain retardation increased ( OR = 3. 306， 95% CI : 1. 080 －10. 124) . Conclusion Young children with suspected neurobehavioral delays were more likely to have delayed development in language domain than in other domains，boys had lower DQ in language domain and personal-social domain than girls，and the development of young children via CS was slower than that via NVD．Fo- cus should be on the language development of young children especially on the language and personal-social devel- opment of boys．Carefully chose delivery way．Focus should be placed on assessment of young children's comprehen- sive neurobehavioral development in early time.