Vitamin D in Acute and Critically Sick Children with a Subgroup of Sepsis and Mortality: A Meta-Analysis.

A meta-analysis study was performed to evaluate the relationship between vitamin D deficiency children and sepsis and acute and critically mortality. Through a systematic literature search up to December 2019, 23 studies with 4451 children, 2500 children with vitamin D deficiency were identified reporting relationships between vitamin D deficiency and sepsis and/or acute and critical care unit mortality (six sepsis only, four acute and critically mortality only and 13 both sepsis and acute and critically mortality). Odd ratio (OR) with 95% confidence intervals (CIs) was calculated comparing vitamin D deficiency children to normal vitamin D children on the bases of sepsis and mortality in acute and critical care units using the dichotomous method with a random effect model. No significant difference was found between males and females in pooled studies all together (OR, 0.72; 95% CI, 0.43-1.22). Vitamin D deficiency children (OR, 2.24; 95% CI, 1.42-3.53) had higher sepsis compared to normal vitamin D children. Also, vitamin D deficiency children (OR, 1.77; 95% CI, 1.26-2.49) had higher acute and critically mortality compared to normal vitamin D children but not as much as that in sepsis. The extent of increased sepsis was higher than that in acute and critically mortality. The impact of vitamin D deficiency in children was observed in all populations. Based on this meta-analysis, vitamin D deficiency in children may have an independent-relationship with up to 2.24 fold risk of sepsis and acute and critical care unit mortality. This relationship forces us to recommend checking vitamin D concentration in all critically ill children.

lncRNA C2dat1 Promotes Cell Proliferation, Migration, and Invasion by Targeting miR-34a-5p in Osteosarcoma Cells.

Osteosarcoma is a highly aggressive malignant bone tumor with poor prognosis. Evidence has suggested that lncRNAs are deregulated in multiple cancers. In this study, we investigated the role of the lncRNA C2dat1 on the biological functions of osteosarcoma cells. The expressions of C2dat1, miR-34a-5p, and Sirt1 in human osteosarcoma cells were altered by transfection with their specific vectors/shRNA or mimic/inhibitor. Cell viability, migration, invasion, and apoptosis were assessed posttransfection. The mRNA and protein levels of C2dat1, miR-34a-5p, and Sirt1 were detected by qRT-PCR and Western blot. The results showed that C2dat1 suppression reduced cell viability, invasion, and migration, whereas it increased cell apoptosis in OS-732 cells. The expression of miR-34a-5p was downregulated when C2dat1 was overexpressed, whereas it negatively regulated Sirt1 expression. miR-34a-5p overexpression inhibited cell viability, migration, and invasion and promoted cell apoptosis in osteosarcoma cells by downregulation of Sirt1. Furthermore, miR-34a-5p overexpression deactivated the p38/ERK/AKT and Wnt/ß-catenin signaling pathways by inhibition of Sirt1.

ß-Aescin shows potent antiproliferative activity in osteosarcoma cells by inducing autophagy, ROS generation and mitochondrial membrane potential loss.

PURPOSE: Osteosarcoma is one of the frequent bone tumor affecting mainly children and is associated with considerable mortality. The limited availability of anticancer drugs and less efficacious treatment options have led to poor survival rates of patients with osteosarcoma. Therefore, there is need to look for more viable treatment options and against this backdrop, natural products may prove handy. Therefore the aim of the present study was to evaluate the anticancer activity of a natural product of plant origin, ß-aescin, against U2OS human osteosarcoma cells. METHODS: U205 human osteosarcoma cell line was used in this study. Antiproliferative activity was determined by MTT assay. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were evaluated by flow cytometry. Autophagy was detected by monodansylcadaverine (MDC) staining and immunofluorescence. Protein expression was examined by western blotting. RESULTS: The results indicated that ß-aescin showed significant anticancer activity against U2OS human osteosarcoma cells and exhibited an IC50 of 40 µM. ß-aescin treatment caused significant increase in ROS and decrease in the MMP. The anticancer effect of ß-aescin was found to be due mainly to autophagic cell death as evidenced from MDC staining and immunofluorescence. Moreover, ß-aescin caused significant increase in the expression levels of LC3- II protein in U2OS osteosarcoma cells in a time and dosedependent manner. CONCLUSION: Taken together we propose that ß-aescin may prove a lead molecule in the management of osteosarcoma and deserves further research efforts.

MicroRNA-223 alleviates lipopolysaccharide-induced PC-12 cells apoptosis and autophagy by targeting RPH1 in spinal cord injury.

Spinal cord injury (SCI) is one of the most devastating diseases. MicroRNAs (miRNAs) are recognized as key regulators in SCI; however, the role of miR-223 in SCI remains unclear. Herein, our study aimed to explore the effect of miR-223 on lipopolysaccharide (LPS)-induced injury to PC-12 cells. PC-12 cells were treated with different concentrations of LPS, and then cell viability, apoptosis, apoptosis-related factors and autophagy-related factors were analyzed by CCK-8, flow cytometry and western blot. Subsequently, miR-223 mimic, miR-223 inhibitor, pEX-RPH1, sh-RPH1 and corresponding controls were transfected into PC-12 cells followed by 5 µg/ml of LPS treatment. Cell viability, apoptosis, apoptosis-related and autophagy-related factors were analyzed again. A target gene of miR-223 was validated by dual-luciferase assay. Besides, the main factors expressions of mTOR and NF-κB signal pathways were measured by western blot. LPS reduced cell viability but increased apoptotic cells rate, up-regulated Bax, cleaved-caspase-3, cleaved-caspase-9, LC-II and Beclin-1, and down-regulated Bcl-2 and p62 expressions in a dose-dependent way. Additionally, miR-223 overexpression promoted cell viability but inhibited apoptosis, and autophagy in LPS-stimulated PC-12 cells. RPH1 was a direct target of miR-223, and RPH1 exhibited contrary impacts to miR-223 on LPS-induced cell apoptosis and autophagy. Besides, the promoting effects of miR-223 suppression on cell apoptosis and autophagy were relieved by RPH1 silence. Furthermore, miR-223 blocked LPS-induced mTOR and NF-κB pathways by down-regulation of RPH1. MiR-223 improved cell viability but declined apoptosis and autophagy by targeting RPH1 and blocked mTOR and NF-κB pathways in LPS challenged PC-12 cells.