Regulation of the PD-1/PD-L1 Axis and NK Cell Dysfunction by Exosomal miR-552-5p in Gastric Cancer.

OBJECTIVE: NK cells play a vital role in tumor immune resistance. Various factors affect NK cell activity. While NK cell dysfunction has been observed in numerous malignancies, the underlying mechanisms in gastric cancer remain unclear. METHOD: Flow cytometry was used to identify the phenotypic distribution and expression of activated receptors on NK cells. ELISA was used to determine the expression of cytokines. We examined the expression of NK cell-related genes and explored their association with survival and prognosis. Additionally, we conducted PCR detection of miR-552-5p expression levels in plasma exosomes of patients and investigated its correlation with phenotypic distribution and activated receptors. We used flow cytometry and ELISA to verify the role of miR-552-5p in NK cell dysfunction. Furthermore, we investigated the potential role of PD-1/PD-L1 in regulating NK cell dysfunction in patients' cells. RESULTS: We observed a significant decrease in the percentage of NKG2D and NKp30 and IFN-γ and TNF-α in patients than in healthy volunteers. Patients with low levels of CD56, CD16, NKG2D, and NKP46 exhibited poorer survival prognoses. Moreover, increased expression levels of plasma exosomal miR-552-5p in patients were negatively associated with NK cell phenotypic distribution and activated receptor expression. MiR-552-5p downregulated the secretion of perforin, granzyme, and IFN-γ as well as the expression of NKp30, NKp46, and NKG2D. Additionally, it suppressed the cytotoxicity of NK cells. The inhibitory effect of miR-552-5p, on NK cell function was reversed when anti-PD-L1 antibodies were used. CONCLUSION: Exosomal miR-552-5p targets the PD-1/PD-L1 axis, leading to impaired NK cell function.

Morphological and hemodynamic changes of sciatic nerves and their vasa nervorum during circular compression and relaxation.

The main aim of this study was to evaluate the biomechanical and hemodynamic responses of vasa nervorum under transverse circular compression. In situ compress-and-hold experiments were performed on the sciatic nerves of healthy and diabetic rats, and the blood flow within the vasa nervorum was observed using Doppler-optical coherence tomography. A new technique was developed to obtain the time-course of the cross sectional area and the morphology of the vasa nervorum from the tomographic images. A quasi-linear viscoelastic model was used to investigate the overall biomechanical properties of the nerves, and a two-dimensional three-layered finite element model was constructed to analyze the distribution of stress and the morphological changes during the compression-relaxation process. The results showed that the lumenal area of vasa nervorum was reduced in the compression stage, especially for the diabetic nerves. The reduction was greater than 70% when the reduction of the nerve diameter was only 10%. The quasi-linear viscoelastic model showed that normal nerves were more elastic but less viscous than the diabetic nerves. The finite element analyses demonstrated that perineurium could sustain more stress than other layers, while epineurium served as a cushion to protect vasa nervora. In addition, there were regions within epineurium with less stress, so that vasa nervora in these saddle regions were less deformed. The vasa nervorum in diabetic rats was more prone to compression and reduction of blood flow than that of the normal rats. The histological studies supported the simulation results.