Ferroptosis inducers: A new frontier in cancer therapy.

Ferroptosis represents a non-apoptotic form of programmed cell death characterized by iron-dependent lipid peroxidation. This cell death modality not only facilitates the direct elimination of cancer cells, but also enhances their susceptibility to other pharmacological anti-cancer agents. The burgeoning interest in ferroptosis has been driven by a growing body of evidence that underscores the efficiency and minimal toxicity of ferroptosis inducers. Traditional inducers, such as erastin and RSL3 have shown substantial promise in clinical applications due to their potent therapeutic effects. Their significant potential of these inducers has spurred the development of a variety of small molecule ferroptosis inducers. These novel inducers boast an enhanced structural variety, improved metabolic stability, the capability to initiate ferroptosis without triggering apoptosis, making them well-suited for in vivo use. Despite these advancements, challenges still remain, particularly concerning the drug delivery, tumor specificity, and circulation duration of these small molecules in vivo. Addressing these challenges, contemporary research has pivoted towards innovative delivery systems tailored for ferroptosis inducers to facilitate precise, targeted, and synegestic therapeutic delivery. This review scrutinizes the latest progress in small molecule ferroptosis inducers and nano drug delivery systems geared towards ferroptosis sensitization. Furthermore, it delineated the prospective therapeutic advantages and the existing hurdles in the development of ferroptosis inducers for malignant tumor treatment.

Weekend effect on the incidence and outcomes of cardiac surgery associated - acute kidney injury.

BACKGROUND: The effects of surgical day (workdays or weekends) on occurrence and outcome of cardiac surgery associated -acute kidney injury (CSA-AKI) remains unclear. This study aimed to compare the incidence and short-term outcomes of CSA-AKI in patients undergoing surgery on workdays and weekends. MATERIALS AND METHODS: Patients who underwent cardiac surgery from July 2020 to December 2020 were retrospectively enrolled in this study. These patients were divided into a weekend group and workday group. The primary endpoint was the incidence of CSA-AKI. The secondary endpoints included renal function recovery and in-hospital mortality. The logistic regression model was used to explore the risk factors for CSA-AKI. Stratification analysis was performed to estimate the association between CSA-AKI and weekend surgery stratified by emergency surgery. RESULTS: A total of 1974 patients undergoing cardiac surgery were enrolled. The incidence of CSA-AKI in the weekend group was significantly higher than that in the workday group (42.8% vs. 34.7%, P = 0.038). Further analysis of patients with CSA-AKI showed that there was no difference in renal function recovery between the workday AKI group and weekend AKI group. There was no difference in in-hospital mortality between the weekend group and workday group (3.6% vs. 2.4%, P = 0.327); however, the in-hospital mortality of the weekend AKI group was significantly higher than that of the workday AKI group (8.5% vs. 2.9%, P = 0.014). Weekend surgery and emergency surgery were independent risk factors for CSA-AKI. The multiplicative model showed an interaction between weekend surgery and emergency surgery; weekend surgery was related to an increased risk of AKI among patients undergoing emergency surgery [adjusted OR (95% CI): 1.96 (1.012-8.128)]. CONCLUSIONS: The incidence of CSA-AKI in patients undergoing cardiac surgery on weekends was significantly higher compared to that in patients undergoing cardiac surgery on workdays. Weekend surgery did not affect the in-hospital mortality of all patients but significantly increased the mortality of AKI patients. Weekend surgery and emergency surgery were independent risk factors for CSA-AKI. Weekend emergency surgery significantly increased the risk of CSA-AKI.

MicroRNA-383 acts as a tumor suppressor in colorectal cancer by modulating CREPT/RPRD1B expression.

CREPT (Cell-cycle-related and expression-elevated protein in tumor)/RPRD1B, a novel protein that enhances the transcription of Cyclin D1 to promote cell proliferation during tumorigenesis, was demonstrated highly expressed in most of tumors. However, it remains unclear how CREPT is regulated in colorectal cancers. In this study, we report that miR-383 negatively regulates CREPT expression. We observed that CREPT was up-regulated but the expression of miR-383 was down regulated in both colon cancer cell lines and colon tumor tissues. Intriguingly, we found that enforced expression of miR-383 inhibited the expression of CREPT at both the mRNA and protein level. Using a luciferase reporter, we showed that miR-383 targeted the 3'-UTR of CREPT mRNA directly. Consistently we observed that over expression of miR-383 shortened the half-life of CREPT mRNA in varieties of colorectal cancer cells. Furthermore, restoration of miR-383 inhibited cell growth and colony formation of colon cancer cells accompanied by inhibition of expression of CREPT and related downstream genes. Finally, we demonstrated that stable over expression of miR-383 in colon cancer cells decreased the growth of the tumors. Our results revealed that the abundant expression of CREPT in colorectal cancers is attributed to the decreased level of miR-383. This study shed a new light on the potential therapeutic therapy strategy for colorectal cancers using introduced miRNA.