Propofol maintains Th17/Treg cell balance in elderly patients undergoing lung cancer surgery through GABAA receptor.

Propofol is widely used in clinical anesthesia due to its advantages of rapid onset and less adverse reactions. This study focused on the role of propofol in the balance of Th17/Treg in elderly patients with lung cancer during perioperative period. Patients undergoing lung cancer surgery were anesthetized by propofol or sevoflurane. Veinal blood was collected at different time points to evaluate the changes of Th17/Treg cell. Propofol better maintained the balance of Th17/Treg in vivo. The peripheral blood of patients with lung cancer was collected in vitro before surgery. Cluster of differentiation (CD)4+ T cells were obtained and then treated with propofol at different concentrations and γ-aminobutyric acid A (GABAA) receptor antagonists. Propofol affected Th17/Treg cell balance by increasing Th17 cells, decreasing Treg cells, thus elevating Th17/Treg ratio, and inhibited invasion and migration of lung cancer cells through GABAA receptor, which was counteracted by GABAA receptor inhibitors. Subsequently, tumor in situ model of lung cancer in aged mice was established. Propofol anesthetized mice had lower change of Th17/Treg ratio, higher survival rate and less metastasis. In brief, propofol regulated balance of Th17/Treg in elderly patients undergoing lung cancer surgery through GABAA receptor. Additionally, propofol could inhibit metastasis of lung cancer.

Propofol maintains Th17/Treg cell balance and reduces inflammation in rats with traumatic brain injury via the miR­145­3p/NFATc2/NF­κB axis.

Propofol is a commonly used intravenous anesthetic. The aim of the study was to examine the mechanism of propofol in traumatic brain injury (TBI) by regulating interleukin (IL)­17 activity and maintaining the Th17/Treg balance. A rat model with moderate TBI was established using the weight­drop method. Rats with TBI were regularly injected with propofol and their brain injuries were monitored. The peripheral blood of rats was collected to measure the Th17/Treg ratio. MicroRNA (miR)­145­3p expression was detected in the brain tissues of rats and antagomiR­145­3p was injected into the lateral ventricles of their brains to verify the effect of miR­145­3p on brain injury. The downstream target of miR­145­3p was predicted. The targeting relationship between miR­145­3p and nuclear factor of activated T cells c2 (NFATc2) was confirmed. NFATC2 expression and phosphorylation of NF­κB pathway­related proteins were measured. Propofol alleviated brain injury in rats with TBI and maintained the Th17/Treg balance. Propofol upregulated miR­145­3p expression in rat brains, while the inhibition of miR­145­3p reversed the effect of propofol on brain injury. A binding relationship was observed between miR­145­3p and NFATc2. Furthermore, propofol decreased the phosphorylation of p65 and IκBα, and inhibited activation of the NF­κB pathway in the brains of rats with TBI. In conclusion, propofol maintained Th17/Treg balance and reduced inflammation in the rats with TBI via the miR­145­3p/NFATc2/NF­κB axis.

Pulmonary endoderm, second heart field and the morphogenesis of distal outflow tract in mouse embryonic heart.

The second heart field (SHF), foregut endoderm and sonic hedgehog (SHH) signaling pathway are all reported to associate with normal morphogenesis and septation of outflow tract (OFT). However, the morphological relationships of the development of foregut endoderm and expression of SHH signaling pathway members with the development of surrounding SHF and OFT are seldom described. In this study, serial sections of mouse embryos from ED9 to ED13 (midgestation) were stained with a series of marker antibodies for specifically highlighting SHF (Isl-1), endoderm (Foxa2), basement membrane (Laminin), myocardium (MHC) and smooth muscle (α-SMA) respectively, or SHH receptors antibodies including patched1 (Ptc1), patched2 (Ptc2) and smoothened, to observe the spatiotemporal relationship between them and their contributions to OFT morphogenesis. Our results demonstrated that the development of an Isl-1 positive field in the splanchnic mesoderm ventral to foregut, a subset of SHF, is closely coupled with pulmonary endoderm or tracheal groove, the Isl-1 positive cells surrounding pulmonary endoderm are distributed in a special cone-shaped pattern and take part in the formation of the lateral walls of the intrapericardial aorta and pulmonary trunk and the transient aortic-pulmonary septum, and Ptc1 and Ptc2 are exclusively expressed in pulmonary endoderm during this Isl-l positive field development, suggesting special roles played in inducing the Isl-l positive field formation by pulmonary endoderm. It is indicated that pulmonary endoderm plays a role in the development and specification of SHF in midgestation, and that pulmonary endoderm-associated Isl-l positive field is involved in patterning the morphogenesis and septation of the intrapericardial arterial trunks.