Ferroptosis is a newly defined programmed cell death process with the hallmark of the accumulation of iron‐dependent lipid peroxides. The term was first coined in 2012 by the Stockwell Lab, who described a unique type of cell death induced by the small molecules erastin or RSL3. Ferroptosis is distinct from other already established programmed cell death and has unique morphological and bioenergetic features. The physiological role of ferroptosis during development has not been well characterized. However, ferroptosis shows great potentials during the cancer therapy. Great progress has been made in exploring the mechanisms of ferroptosis. In this review, we focus on the molecular mechanisms of ferroptosis, the small molecules functioning in ferroptosis initiation and ferroptosis sensitivity in different cancers. We are also concerned with the new arising questions in this particular research area that remains unanswered.

FOXO3a is a member of the FOXO subfamily of forkhead transcription factors that mediate a variety of cellular processes including apoptosis, proliferation, cell cycle progression, DNA damage and tumorigenesis. It also responds to several cellular stresses such as UV irradiation and oxidative stress. The function of FOXO3a is regulated by a complex network of processes, including post-transcriptional suppression by microRNAs (miRNAs), post-translational modifications (PTMs) and protein–protein interactions. FOXO3a is widely implicated in a variety of diseases, particularly in malignancy of breast, liver, colon, prostate, bladder, and nasopharyngeal cancers. Emerging evidences indicate that FOXO3a acts as a tumor suppressor in cancer. FOXO3a is frequently inactivated in cancer cell lines by mutation of the FOXO3a gene or cytoplasmic sequestration of FOXO3a protein. And its inactivation is associated with the initiation and progression of cancer. In experimental studies, overexpression of FOXO3a inhibits the proliferation, tumorigenic potential, and invasiveness of cancer cells, while silencing of FOXO3a results in marked attenuation in protection against tumorigenesis. The role of FOXO3a in both normal physiology as well as in cancer development have presented a great challenge to formulating an effective therapeutic strategy for cancer. In this review, we summarize the recent findings and overview of the current understanding of the influence of FOXO3a in cancer development and progression.

Acute myocardial infarction is the leading cause of cardiovascular‑related mortality and chronic heart failure worldwide. As regards treatment, the reperfusion of ischemic tissue generates irreversible damage to the myocardium, which is termed ‘cardiac ischemia‑reperfusion (IR) injury’. Due to the large number of mitochondria in cardiomyocytes, an increasing number of studies have focused on the roles of mitochondria in IR injury. The primary causes of IR injury are reduced oxidative phosphorylation during hypoxia and the increased production of reactive oxygen species (ROS), together with the insufficient elimination of these oxidative species following reperfusion. IR injury includes the oxidation of DNA, incorrect modifications of proteins, the disruption of the mitochondrial membrane and respiratory chain, the loss of mitochondrial membrane potential (∆Ψm), Ca2+ overload, mitochondrial permeability transition pore formation, swelling of the mitochondria, and ultimately, cardiomyocyte necrosis. The present review article discusses the molecular mechanisms of IR injury, and summarizes the metabolic and dynamic changes occurring in the mitochondria in response to IR stress. The mitochondria are strongly recommended as a target for the development of therapeutic agents; however, the appropriate use of agents remains a challenge.

Gastric cancer (GC) is one of the most prevalent malignant tumor types and the third leading cause of cancer-related death worldwide. Its morbidity and mortality are very high due to a lack of understanding about its pathogenesis and the slow development of novel therapeutic strategies. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs with a length of more than 200 nt. They play crucial roles in a wide spectrum of physiological and pathological processes by regulating the expression of genes involved in proliferation, differentiation, apoptosis, cell cycle, invasion, metastasis, DNA damage, and carcinogenesis. The aberrant expression of lncRNAs has been found in various cancer types. A growing amount of evidence demonstrates that lncRNAs are involved in many aspects of GC pathogenesis, including its occurrence, metastasis, and recurrence, indicating their potential role as novel biomarkers in the diagnosis, prognosis, and therapeutic targets of GC. This review systematically summarizes the biogenesis, biological properties, and functions of lncRNAs and highlights their critical role and clinical significance in GC. This information may contribute to the development of better diagnostics and treatments for GC.

ROS functions as a second messenger and modulates multiple signaling pathways under the physiological conditions. However, excessive intracellular ROS causes damage to the molecular components of the cell, which promotes the pathogenesis of various human diseases. Cardiovascular diseases are serious threats to human health with extremely high rates of morbidity and mortality. Dysregulation of cell death promotes the pathogenesis of cardiovascular diseases and is the clinical target during the disease treatment. Numerous studies show that ROS production is closely linked to the cell death process and promotes the occurrence and development of the cardiovascular diseases. In this review, we summarize the regulation of intracellular ROS, the roles of ROS played in the development of cardiovascular diseases, and the programmed cell death induced by intracellular ROS. We also focus on anti-ROS system and the potential application of anti-ROS strategy in the treatment of cardiovascular diseases.

Aims: Cardiomyocyte death critically contributes to the pathogenesis of cardiac disorders, such as myocardial infarction, heart failure, and cardiac ischemia/reperfusion (I/R) injury. As one of the main forms of cardiac cell death, necrosis plays a critical role in heart diseases. Multiple signaling pathways of necrosis have been demonstrated, in which death receptors, receptor-interacting serine/threonine-protein 1 and 3 kinases, and cyclophilin-D (CypD) have been deeply implicated. However, the fundamental mechanism underlying myocardial necroptosis, especially the mitochondrial permeability transition pore (mPTP)-CypD-dependent death pathway, is poorly understood. Parkin functions as an E3 ubiquitin protein ligase that mainly mediates mitophagy cascades. As yet, it is not clear whether Parkin participates in regulating necrosis and myocardial I/R injury. Results: Here, our results showed that Parkin mediated mitophagy and inhibited necrosis under oxidative stress. In further exploring the underlying mechanisms, we found that Parkin suppressed mPTP opening by catalyzing the ubiquitination of CypD in necrotic cascades, which were not involved in Parkin-regulated mitophagy. Parkin inhibited necrosis, reduced myocardial I/R injury, and improved cardiac function. Innovation: Our present work reveals a highlighted connection between the mitochondrial matrix-localized Parkin and the mPTP-CypD-dependent necrotic signaling pathway in cardiac injury. Conclusion: Our results revealed a novel myocardial necrotic regulating model composed of Parkin, CypD, and mPTP, which may provide potential therapeutic targets and strategies to modulate the levels of these molecules.