PIEZO1 Promotes the Migration of Endothelial Cells via Enhancing CXCR4 Expression under Simulated Microgravity.

Exposure to microgravity during spaceflight induces the alterations in endothelial cell function associated with post-flight cardiovascular deconditioning. PIEZO1 is a major mechanosensitive ion channel that regulates endothelial cell function. In this study, we used a two-dimensional clinostat to investigate the expression of PIEZO1 and its regulatory mechanism on human umbilical vein endothelial cells (HUVECs) under simulated microgravity. Utilizing quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, we observed that PIEZO1 expression was significantly increased in response to simulated microgravity. Moreover, we found microgravity promoted endothelial cells migration by increasing expression of PIEZO1. Proteomics analysis highlighted the importance of C-X-C chemokine receptor type 4(CXCR4) as a main target molecule of PIEZO1 in HUVECs. CXCR4 protein level was increased with simulated microgravity and decreased with PIEZO1 knock down. The mechanistic study showed that PIEZO1 enhances CXCR4 expression via Ca2+ influx. In addition, CXCR4 could promote endothelial cell migration under simulated microgravity. Taken together, these results suggest that the upregulation of PIEZO1 in response to simulated microgravity regulates endothelial cell migration due to enhancing CXCR4 expression via Ca2+ influx.

IFITM3 reduces infectious bursal disease virus proliferation by regulating interferon expression.

Interferon-inducible transmembrane protein 3 (IFITM3), a member of the interferon-stimulating factor (ISG) family, has various antiviral functions. Infectious bursal disease virus (IBDV) mainly invades the bursa of Fabricius in chickens, causing a reduction in their immunity and resulting in death from secondary infections. Our previous study found that IBDV infection promotes the expression of chicken IFITM3. However, the role of chicken IFITM3 in IBDV infection remains unknown. To explore this role, the overexpression vector for IFITM3 was constructed and transfected into HD-11 and DF-1 cells. The results showed that the overexpression of IFITM3 significantly reduced IBDV proliferation. While the IBDV proliferation increased when IFITM3 was inhibited by using siRNA. To further explore the mechanism by which IFITM3 reduces IBDV proliferation, the effects of IFITM3 on interferon (IFN) were investigated. Transfecting the constructed IFITM3 vectors into HD-11 and DF-1 cells demonstrated that IFITM3 promoted the expression of IFN-α, IFN-ß, and IFN-γ. To investigate the mechanism by which IFITM3 regulates IFN expression, the effects of IFITM3 on IFN production were explored. The results showed that the IKB gene mainly affected the regulatory effects of IFITM3 on IFN. Taken together, IFITM3 may reduce viral proliferation by regulating changes in IFNs, and this process may involve a positive feedback effect of IFITM3 on IFN. IKB plays an important role in the regulation of IFN effects by IFITM3.

Hypoxic acclimatization training improves the resistance to motion sickness.

Objective: Vestibular provocation is one of the main causes of flight illusions, and its occurrence is closely related to the susceptibility of motion sickness (MS). However, existing training programs have limited effect in improving the resistance to motion sickness. In this study, we investigated the effects of hypoxia acclimatization training (HAT) on the resistance to motion sickness. Methods: Healthy military college students were identified as subjects according to the criteria. MS model was induced by a rotary chair. Experimental groups included control, HAT, 3D roller training (3DRT), and combined training. Results: The Graybiel scores were decreased in the HAT group and the 3DRT group and further decreased in the combined training group in MS induced by the rotary chair. Participants had a significant increase in blood pressure after the rotary chair test and a significant increase in the heart rate during the rotary chair test, but these changes disappeared in all three training groups. Additionally, LFn was increased, HFn was decreased, and LF/HF was increased accordingly during the rotary chair test in the control group, but the changes of these three parameters were completely opposite in the three training groups during the rotary chair test. Compared with the control group, the decreasing changes in pupillary contraction velocity (PCV) and pupillary minimum diameter (PMD) of the three training groups were smaller. In particular, the binocular PCV changes were further attenuated in the combined training group. Conclusion: Our research provides a possible candidate solution for training military pilots in the resistance to motion sickness.