MiR-339-3p aggravates rat vascular inflammation induced by AT1R autoantibodies by down-regulating BKα protein expression

The abnormality of large-conductance calcium-activated potassium channels (BK channels) is an important factor in inducing vascular inflammation. BK channel agonists can readily recover BK channel function and improve vascular inflammation. However, it is not clear how to improve BK dysfunction caused by downregulation of BK channel protein expression. This study found that angiotensin II-1 receptor autoantibodies (AT1-AA), which are widely present in the body of various types of cardiovascular diseases, can down-regulate the expression of BK channel protein and induce vascular inflammation. Further research found that the elevated neural precursor cells expressed developmentally downregulated 4-like (NEDD4L) protein level is involved in the down-regulation of BK channel α subunit (BKα) protein level by AT1-AA. Bioinformatics analysis and experiments have confirmed that miR-339-3p plays an irreplaceable role in the high expression of NEDD4L and the low expression of BKα, and aggravates the vascular inflammation induced by AT1-AA. Overall, AT1-AA increased miR-339-3p expression (targeting BKα via the miR-339-3p/NEDD4L axis or miR-339-3p alone), reduced BKα protein expression in VSMCs, and induced vascular inflammation. The results of the study indicate that miR-339-3p may become a new target for reversing vascular inflammation in AT1-AA-positive patients.

Greater Number of Microglia in Telencephalic Proliferative Zones of Human and Non-Human Primate Compared to Other Vertebrate Species

Microglial cells, the innate immune cells of the brain, are derived from yolk sac precursor cells, begin to colonize the telencephalon at the onset of cortical neurogenesis, and occupy specific layers including the telencephalic proliferative zones. Microglia are an intrinsic component of cortical germinal zones, establish extensive contacts with neural precursor cells (NPCs) and developing cortical vessels, and regulate the size of the NPC pool through mechanisms that include phagocytosis. Microglia exhibit notable differences in number and distribution in the prenatal neocortex between rat and Old World nonhuman primate telencephalon, suggesting that microglia exhibit distinct properties across vertebrate species. To begin addressing this subject we quantified the number of microglia and NPCs in proliferative zones of the fetal human, rhesus monkey, ferret, and rat, and the pre-hatch chick and turtle telencephalon. We show that the ratio of NPCs to microglia varies significantly across species. Few microglia populate the pre-hatch chick telencephalon, but the number of microglia approaches that of NPCs in fetal human and non-human primate telencephalon. These data demonstrate that microglia are in a position to perform similar functions in a number of vertebrate species, but more heavily colonize proliferative zones of fetal human and rhesus monkey telencephalon.

Differences in the Cytotoxic Effects of Multi-Walled Carbon Nanotubes on Two- and Three-Dimensionally Cultured Human Neural Precursor Cells and Rat Brain Slices

Carbon nanotubes (CNTs) are used in batteries, nano-electronic devices, fuel cells, and biosensors as they can be used to make these devices more biocompatible; moreover, various compounds can be attached to these CNTs. Although multi-walled carbon nanotubes (MWCNTs) have been used in biosensors for the detection of specific proteins and neurotransmitters, they are not well understood. The present study addressed the difference between the cytotoxic effects of different types of MWCNTs by testing them on two dimensional (2D) and 3D-cultivated human neural precursor cells (hNPCs). We also evaluated the apoptotic damage caused by these MWCNTs using rat brain slices. Our results confirmed that there was significant cytotoxic effect of MWCNT, as shown by the damage caused to the 2D cultured cells. However, the cell death seen in the 3D cultured cells treated with MWCNT was significantly lower than that of the 2D cultivated cells. Furthermore, the 3D cell cytotoxicity assay showed similar results after MWCNT 1/2 treatment and decreased slightly after MWCNT 3/4 treatment, except when treated with 10 ng/ml of MWCNT 3 and 1 g/ml of MWCNT 4. Western blot results using brain slices treated with MWCNTs showed that the expressions of SAPK/JNK, Caspase 3, and Caspase 8 were not significantly different compared to those in the control. In conclusion, MWCNTs had a stable effect on the 3D cultured cells or brain slices, consistent with the results seen in the in vivo system, but caused remarkable damage to the 2D cultured cells that were observed as a flat structure