Identification and characterization of ferroptosis-related genes in therapy-resistant gastric cancer.

Therapy resistance in gastric cancer poses ongoing challenges, necessitating the identification of ferroptosis-related genes linked to overall survival for potential therapeutic insights. The purpose of the study was to identify ferroptosis-related genes contributing to therapy resistance in gastric cancer and explore their associations with overall survival. Differentially expressed ferroptosis-related genes were identified in therapy-resistant versus therapy-responsive gastric cancer patients. Hub genes were selected from these genes. Enrichment analysis focused on oxidative stress and ROS metabolism. Validation was conducted in a TCGA stomach adenocarcinoma dataset. A hub gene-based risk model (DUSP1/TNF/NOX4/LONP1) was constructed and assessed for overall survival prediction. Associations with the tumor immune microenvironment were examined using the ESTIMATE algorithm and correlation analysis. Ten hub genes were identified, enriched in oxidative stress and ROS metabolism. Validation confirmed their aberrant expressions in the TCGA dataset. The hub gene-based risk model effectively predicted overall survival. High G6PD/TNF expression and low NOX4/SREBF1/MAPK3/DUSP1/KRAS/SIRT3/LONP1 expression correlated with stromal and immune scores. KRAS/TNF/MAPK3 expression positively correlated with immune-related SREBF1/NOX4 expression. DUSP1/NOX4/SREBF1/TNF/KRAS expression was associated with immune cell infiltration. The hub gene-based risk model (DUSP1/TNF/NOX4/LONP1) shows promise as an overall survival predictor in gastric cancer. Ferroptosis-related hub genes represent potential therapeutic targets for overcoming therapy resistance in gastric cancer treatment.

A Narrative Review of STAT Proteins in Diabetic Retinopathy: From Mechanisms to Therapeutic Prospects.

Diabetic retinopathy (DR), a blinding disease, is one of the high-incidence chronic complications of diabetes. However, the current treatment for DR is mainly based on advanced pathological changes, which cannot reverse pre-existing retinal tissue damage and visual impairment. Signal transducer and activator of transcription (STAT) proteins are essential in DR through early and late stages. They participate in the early stage of DR through multiple mechanisms and have a strong proangiogenic effect in the late stage. Inhibiting STAT proteins activity has also achieved a significant effect in reversing the pathological changes of DR. Thus, STAT proteins are expected to be an effective therapeutic target in the early stage of DR and can make up for inadequate late treatment. This review introduces the structure, signal transduction mode, and biological functions of STAT proteins in detail and focuses on their role in the mechanism of DR. We also summarize the current research on STAT-related biological agents in DR, aiming to provide a theoretical basis for the treatment of DR.

MiR-331-3p Inhibition of the Hepatocellular Carcinoma (HCC) Bel-7402 Cell Line by Down-Regulation of E2F1.

MicroRNAs play an important role in cell proliferation and migration in hepatocellular carcinoma (HCC). In this study, the expression of MiR-331-3p in the liver cancer tissues of 116 patients, and in one normal (HL-7702) and five HCC cell lines (HepG2, SMMC-7721, Bel-7402, QGY-7701 and QGY-7703) was determined by qRT-PCR. Results indicated that MiR-331-3p was significantly repressed in HCC patients and in HCC cell lines, especially in the Bel-7402 cells when compared to normal liver tissue and the normal hepatocyte line, HL-7702. Therefore, artificial MiR-331-3p mimic computationally targeting E2F1 and anti-sense MiR-331-3p inhibitor were designed and used to transfect the Bel-7402 lines. Stable expression and significant inhibition of MiR-331-3p, with clear changes in cell morphology, proliferation and motility, were detected in Bel-7402 cells transfected with MiR-331-3p mimic or inhibitor, respectively. As E2F1 was computationally recognized as the target of MiR-331-3p, the expression of E2F1 in transfected Bel-7402 cells was analyzed by qRT-PCR and Western blotting. Results showed a strong inhibition of E2F1 by MiR-331-3p and further promotion of E2F1 by MiR-331-3p inhibitor in transfected Bel-7402 cells. Flow cytometry analysis showed that the cell ratio was restored to S to G0/1 cell number. Inhibition of E2F1 by MiR-331-3p mimic promoted cell proliferation and migration in Bel-7402. These results demonstrated that MiR-331-3p down-regulated E2F1 to promote cell proliferation and migration in HCC.