Ferroptosis is a novel regulated cell death pattern discovered when studying the mechanism of erastin-killing RAS mutant tumor cells in 2012. It is an iron-dependent programmed cell death pathway mainly caused by an increased redox imbalance but with distinct biological and morphology characteristics when compared to other known cell death patterns. Ferroptosis is associated with various diseases including acute kidney injury, cancer, and cardiovascular, neurodegenerative, and hepatic diseases. Moreover, activation or inhibition of ferroptosis using a variety of ferroptosis initiators and inhibitors can modulate disease progression in animal models. In this review, we provide a comprehensive analysis of the characteristics of ferroptosis, its initiators and inhibitors, and the potential role of its main metabolic pathways in the treatment and prevention of various diseased states. We end the review with the current knowledge gaps in this area to provide direction for future research on ferroptosis.
Small interfering RNA (siRNA) therapeutic is considered to be a promising modality for the treatment of hyperlipidemia. Establishment of a thermostable clinically applicable delivery system remains a most challenging issue for siRNA drug development. Here, a series of ionizable lipid-like materials were rationally designed; 4 panels of lipid formulations were fabricated and evaluated on the basis of four representative structures. The lead lipid (A1-D1-5) was stable at 40°C, and the optimized formulation (iLAND) showed dose and time dual-dependent gene silencing pattern with median effective dose of 0.18 mg/kg. In addition, potent and durable reduction of serum cholesterol and triglyceride were achieved by administering siRNAs targeting
angiopoietin-like 3
or
apolipoprotein C3
(
APOC3
) in high-fat diet–fed mice, db/db mice, and human
APOC3
transgenic mice, respectively, accompanied by displaying ideal safety profiles. Therefore, siRNA@iLAND prepared with thermostable A1-D1-5 demonstrates substantial value for siRNA delivery, hyperlipidemia therapy, and prevention of subsequent metabolic diseases.
Microtubule-associated protein 7 (MAP7) plays an important role in cancer cells. In this study, we identified the prognostic significance of MAP7 expression in cytogenetically normal acute myeloid leukemia (CN-AML) patients (aged <60 years) based on several microarray datasets. In the first group (n = 129), high MAP7 expression (MAP7high) was associated with adverse overall survival (OS; P = 0.0441) and event-free survival (EFS; P = 0.0114) compared with low MAP7 expression (MAP7low). In addition, the prognostic significance of MAP7 was confirmed by European Leukemia Net (ELN) intermediate-I genetic categories and multivariable analysis. In the second independent group of CN-AML patients (aged <60 years), MAP7high was also associated with adverse OS (n = 88, OS; P = 0.00811). To understand the inherent mechanisms of MAP7’s prognosis, we investigated genome-wide gene/microRNA expression signatures associated with MAP7 expression. Several known oncogenic genes/microRNAs and anti-oncogenic genes/microRNAs were disordered in MAP7high CN-AML patients. In conclusion, MAP7high is an adverse prognostic biomarker for CN-AML, which may be attributed to the distinctive genome-wide gene/microRNA expression and related cell signaling pathways.
PurposeWorkplace safety has been a persistent issue for safety-critical organizations. Based on self-verification theory, this study investigates how authentic leadership affects safety behaviors in a collectivistic context.Design/methodology/approachThis research collected 259 matching questionnaires for high-speed railway (HSR) drivers and their supervisors in China. Specifically, HSR drivers were invited to fill in their general perceived authentic leadership, person-organization fit and collectivistic orientation. In addition, their direct supervisors were invited to assess their safety behaviors.FindingsAuthentic leadership exhibits a significant positive impact on safety compliance and safety participation, implying that authentic leadership positively impacts safety behavior. The person-organization fit partially mediated the relationship between authentic leadership and safety behavior (safety compliance and participation). Furthermore, collectivistic orientation moderates the relationship between authentic leadership and person-organization fit.Originality/valueThe findings of this study provide important insights into authentic leadership and person-organization fit for developing effective strategies to improve workplace safety.
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