lnc-MRGPRF-6:1 Promotes ox-LDL-Induced Macrophage Ferroptosis via Suppressing GPX4.

Background: Ferroptosis, a newly discovered mode of cell death, emerges as a new target for atherosclerosis (AS). Long noncoding RNAs (lncRNAs) are involved in the regulation of ferroptosis. In our previous study, lnc-MRGPRF-6:1 was highly expressed in patients with coronary atherosclerotic disease (CAD) and closely associated with macrophage-mediated inflammation in AS. In the present study, we aim to investigate the role of lnc-MRGPRF-6:1 in oxidized-low-density lipoprotein (ox-LDL)-induced macrophage ferroptosis in AS. Methods: Firstly, ox-LDL-treated macrophages were used to simulate macrophage injury in AS. Then, ferroptosis-related biomarkers and mitochondrial morphology were detected and observed in ox-LDL-treated macrophages. Subsequently, we constructed lnc-MRGPRF-6:1 knockdown and overexpression of THP-1-derived macrophages and investigated the role of lnc-MRGPRF-6:1 in ox-LDL-induced ferroptosis. Then human monocytes were isolated successfully and were used to explore the role of lnc-MRGPRF-6:1 in macrophage ferroptosis. Likely, we constructed lnc-MRGPRF-6:1 knockdown and overexpression of human monocyte-derived macrophages and detected the expression levels of ferroptosis-related biomarkers. Then, transcriptome sequencing, literature searching, and following quantitative real-time polymerase chain reaction and western blot were implemented to explore specific signaling pathway in the process. It was demonstrated that lnc-MRGPRF-6:1 may regulate ox-LDL-induced macrophage ferroptosis through glutathione peroxidase 4 (GPX4). Eventually, the correlation between lnc-MRGPRF-6:1 and GPX4 was measured in monocyte-derived macrophages of CAD patients and controls. Results: The ox-LDL-induced injury in macrophages was involved in ferroptosis. The knockdown of lnc-MRGPRF-6:1 could alleviate ox-LDL-induced ferroptosis in macrophages. Meanwhile, the overexpression of lnc-MRGPRF-6:1 could intensify ox-LDL-induced ferroptosis. Furthermore, the knockdown of lnc-MRGPRF-6:1 could alleviate the decrease of GPX4 induced by RAS-selective lethal compounds 3 (RSL-3). These indicated that lnc-MRGPRF-6:1 may suppress GPX4 to induce macrophage ferroptosis. Eventually, lnc-MRGPRF-6:1 was highly expressed in the monocyte-derived macrophages of CAD patients and was negatively correlated with the expression of GPX4. Conclusion: lnc-MRGPRF-6:1 can promote ox-LDL-induced macrophage ferroptosis through inhibiting GPX4.

Novel Immune Microlens Imaging for Detection of Antigen and Antibody.

Detection and analysis of antigen-antibody reaction is one of the most critical detection techniques in the fields of medicine, biology, environmental science, and food safety. Traditional and classical methods for detecting antigen and antibody encounter many problems, such as time-consuming, high cost, and low accuracy. A novel immune microsphere imaging technique by the microlens is used to test the changes of refractive index before and after antigen-antibody reaction. It can quickly perform qualitative and quantitative determination for antigen-antibody reaction without any labeling, premodification, postwashing, and expensive enzymes. Here, we feature and discuss its principle and advantages, structure of a microlens immunoassay instrument, and potential in measuring clinical samples. It is promising to be developed for application to diagnosis of clinical diseases.

Overexpression of NUAK1 is associated with disease-free survival and overall survival in patients with gastric cancer.

Novel (nua) kinase family 1 (NUAK1) is a member of the human adenosine monophosphate-activated protein kinases family, which is overexpressed in multiple human malignancies and thought to be involved in tumor invasion and metastasis ability. Our study is to investigate the association of NUAK1 expression with clinicopathological parameters and prognostic significance of patients with gastric cancer. The expression patterns of the NUAK1 protein in 117 primary archival gastric cancer specimens and 46 adjacent normal epithelial tissues from patients were detected by immunohistochemistry assay. Staining evaluation results were analyzed statistically in relation to various clinicopathological characters, recurrence-free survival and overall survival. High level of NUAK1 expression was detected in gastric cancer, significantly more than in adjacent normal epithelial cells. In gastric cancer, NUAK1 was positively correlated with depth of invasion, lymph node metastasis, pathological stage, surgical resection and histological differentiation. However, no correlations between NUAK1 expression and patients' age, sex, tumor size, location, CA19-9 or CEA were detected. The recurrence-free survival and overall survival were significantly shorter for patients with NUAK1 higher scores than those with NUAK1 lower scores. Multivariate analysis identified NUAK1 was an independent prognostic factor for both recurrence-free survival and overall survival. Our findings provided convincing evidence for NUAK1 overexpression, which was tightly associated with more aggressive tumor behavior and a poor prognosis, indicating that NUAK1 is a valuable molecular biomarker for gastric cancer progression. It might also act as a promising target for both prognostic prediction and therapeutics.