Background. Ferroptosis is a type of iron‐dependent programmed cell death. Ferroptosis has been shown to be a significant factor for the pathogenesis of Parkinson’s disease (PD). However, the mechanism involved in ferroptosis has not been fully elucidated in PD. Methods. Repressor element‐1 silencing transcription factor (REST) and specificity protein 1 (SP1) expressions were monitored by qRT‐PCR. Cell viability, reactive oxygen species (ROS), and mitochondrial injury were validated by CCK‐8, flow cytometry, and transmission electron microscope. The levels of neurons‐related proteins and ferroptosis‐associated proteins were identified by western blot and immunofluorescence assays. The interaction between miR‐494‐3p and REST or SP1 and ACSL4 was analyzed by luciferase, chromatin immunoprecipitation, or EMSA assay. Results. Erastin could dose‐dependently induce neuron injury and ferroptosis of LUHMES cells. miR‐494‐3p overexpression induced ROS production, mitochondrial damage, ferroptosis, and neuron injury in erastin‐induced LUHMES cells. Likewise, miR‐494‐3p inhibition had the opposite effects. We also showed that REST was a target gene of miR‐494‐3p and could repress erastin‐induced ferroptosis, neuron injury, ROS, and mitochondrial injury via SP1 in LUHMES cells. Moreover, we demonstrated that SP1 could interact with ACSL4. We also confirmed that miR‐494‐3p could aggravate the pathological changes of substantia nigra and corpus striatum in the MPTP‐induced PD mouse model. Conclusion. miR‐494‐3p significantly promotes ferroptosis by regulating the REST/SP1/ACSL4 axis in PD. Thus, our results open potential therapeutic targets for PD.
The purpose of this study was to conduct a meta-analysis to assess the association between FSHR Asn680Ser polymorphism and ovarian cancer susceptibility.
Background: The objective of this study is to indirectly compare the efficacy and safety of all currently available neoadjuvant chemoimmunotherapy and perioperative chemoimmunotherapy in randomized controlled trials (RCTs) involving patients with resectable non-small cell lung cancer (NSCLC) to identify optimal treatment regimens. Methods: Eligible studies evaluating neoadjuvant chemoimmunotherapy and perioperative chemoimmunotherapy-based regimens in resectable NSCLC patients were included. Clinical outcomes were extracted for event-free survival (EFS) and overall survival (OS), as well as the incidence of pathological complete response (pCR), major pathological response (MPR), any-grade adverse events (AEs), and treatment-related adverse events (TRAEs) in the Bayesian framework. A subgroup analysis of EFS was conducted according to PD-L1 expression, histological type and reaching pCR or not. Results: We selected eight RCTs involving 3113 patients. Our analysis found no significant differences between perioperative immunotherapy and neoadjuvant immunotherapy in terms of MPR (RR 0.72, 95% CI 0.39 –1.3), pCR (RR 0.73, 95% CI 0.24–2.3), EFS (HR 0.95, 95% CI 0.56–1.7), and OS (HR 95% CI 3.9–4.2). Subgroup analyses revealed that neoadjuvant immunotherapy demonstrated superiority in the programmed death-ligand 1 (PD-L1) high-expression cohort, the non-squamous cell carcinoma cohort, and the non-smoking cohort. Conversely, perioperative immunotherapy ranked first in the PD-L1 low-expression cohort, squamous cell carcinoma cohort, and non-pCR cohort. Conclusions: Our findings indicate that neoadjuvant immunotherapy and perioperative immunotherapy exhibit comparable efficacy in patients with NSCLC. These results provide valuable evidence for guiding the treatment of patients with resectable NSCLC.
The objective of this study is to investigate the correlation of mean platelet volume (MPV), MPV/ platelet count, and monocyte to lymphocyte ratio (MLR) between cervical cancer patients and healthy people and to evaluate the value of those parameters in early diagnosis of cervical cancer. The study population included 137 cervical cancer patients undergoing hysterectomy and 113 healthy controls. The clinical features (age, pathology type, tumor staging, and tumor size) were collected from the hospital information system. The hematology parameters (white blood cell, red blood cell, hemoglobin, platelet count, neutrophil, lymphocyte, monocyte, mean platelet volume, platelet distribution width) are obtained in the laboratory information system. We found that the monocyte count and MLR value are higher in the cervical cancer group. The MPV and MPV/platelet are lower in the cervical cancer group. The receiver operating characteristic (ROC) analysis shows that MPV+MLR can generate a moderate specificity with 71.68%, sensitivity with 65.69%, and AUC with 0.718 to distinguish cervical cancer and healthy people. MPV/platelet and MLR may be helpful for the early diagnosis of cervical cancer. A larger clinical data analysis is necessary to evaluate the diagnostic value of hematologic parameters in cervical cancer.