Extracellular Vesicles Derived from Bone Mesenchymal Stem Cells Carrying circ_0000075 Relieves Cerebral Ischemic Injury by Competitively Inhibiting miR-218-5p and Up-regulating E3 Ubiquitin Ligase SMURF2.

Extracellular vesicle (EV)-encapsulated circRNAs have the potential role in affecting brain disorders. However, the role of circ_0000075 in cerebral ischemic injury remains unclear. Here, we tried to investigate the mechanism of bone marrow mesenchymal stem cell (BMSC)-derived EVs carrying circ_0000075 in the control of cerebral ischemic injury. Initially, a mouse model with cerebral ischemic injury was induced by middle cerebral artery occlusion (MCAO), followed by the determination of circ_0000075 expression. Then, neurons were isolated and subjected to oxygen-glucose deprivation/reperfusion. BMSCs were isolated for extraction of EVs. The correlation among circ_0000075, microRNA (miR)-218-5p, and Smad ubiquitination regulatory factor 2 (SMURF2) was detected with their roles in cerebral ischemic injury analyzed in vivo and in vitro. circ_0000075 was down-regulated in MCAO mice and engineered RVG-EVs were internalized by neurons to up-regulate circ_0000075 expression. Treatment of RVG-circ_0000075-EVs reduced brain tissue damage, increased neuronal count, and significantly curtailed apoptosis rate, suppressing cerebral ischemic injury in vitro and in vivo. miR-218-5p was targeted by circ_0000075 in neurons, which promoted SMURF2 expression. A negative correlation between SMURF2 and transcriptional regulator Yin Yang 1 (YY1) was identified. In vitro experiments further proved that circ_ 00,000 75 could down-regulate the expression of YY1 through SMURF2, and finally relieving cerebral ischemic injury. Collectively, engineered EVs delivered circ_0000075 into brain tissues and increased circ_0000075 expression, which down-regulated miR-218-5p and up-regulated SMURF2, thus alleviating cerebral ischemic injury.

The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis.

OBJECTIVE: Folate and vitamin B12 are two vital regulators in the metabolic process of homocysteine, which is a risk factor of atherothrombotic events. Low folate intake or low plasma folate concentration is associated with increased stroke risk. Previous randomized controlled trials presented discordant findings in the effect of folic acid supplementation-based homocysteine lowering on stroke risk. The aim of the present review was to perform a meta-analysis of relevant randomized controlled trials to check the how different folate fortification status might affect the effects of folic acid supplementation in lowering homocysteine and reducing stroke risk. DESIGN: Relevant randomized controlled trials were identified through formal literature search. Homocysteine reduction was compared in subgroups stratified by folate fortification status. Relative risks with 95 % confidence intervals were used as a measure to assess the association between folic acid supplementation and stroke risk. SETTING: The meta-analysis included fourteen randomized controlled trials, SUBJECTS: A total of 39 420 patients. RESULTS: Homocysteine reductions were 26·99 (sd 1·91) %, 18·38 (sd 3·82) % and 21·30 (sd 1·98) %, respectively, in the subgroups without folate fortification, with folate fortification and with partial folate fortification. Significant difference was observed between the subgroups with folate fortification and without folate fortification (P=0·05). The relative risk of stroke was 0·88 (95 % CI 0·77, 1·00, P=0·05) in the subgroup without folate fortification, 0·94 (95 % CI 0·58, 1·54, P=0·82) in the subgroup with folate fortification and 0·91 (95 % CI 0·82, 1·01, P=0·09) in the subgroup with partial folate fortification. CONCLUSIONS: Folic acid supplementation might have a modest benefit on stroke prevention in regions without folate fortification.

[Municipal wastewater treatment using a composite flocculant made of polyaluminum chloride and polydimethyldiallyammonium chloride].

A composite flocculant (denoted JYF-1), made of polyaluminum chloride (PAC) and polydimethyldiallyammonium chloride (PDMDAAC), was used in jar-tests to simulate the chemically enhanced primary treatment (CEPT) for municipal wastewater. Removal of particles, organic compounds, nitrogen and phosphorus in wastewater was investigated, and the effects of pH and surface overflow rate (SOR) on flocculation were also examined. Electrical charge and distribution of particles in wastewater were analyzed before and after flocculation. Furthermore, the flocculation mechanism and application of JYF-1 in CEPT were discussed. The results demonstrate that JYF-1 performs better than PAC under a wide pH and SOR range. When 8 mg x L(-1) JYF-1 is added, 76.72% COD and 64.31% soluble COD (SCOD) can be removed. About 90% soluble TP (STP), 80% TP and 20% TN can be removed by addition of 12 mg x L(-1) JYF-1. After flocculation, the BOD/COD ratio increases from 0.23 to 0.53, which indicates the biodegradation ability of wastewater is improved. It can be concluded that JYF-1 is a high-efficiency low-cost flocculant, which can improve outlet water quality and produce less sludge without changing the existing equipments and treating process in sewage plants.