Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems can precisely manipulate DNA sequences to change the characteristics of cells and organs, which has potential in the mechanistic research on genes and the treatment of diseases. However, clinical applications are restricted by the lack of safe, targeted and effective delivery vectors. Extracellular vesicles (EVs) are an attractive delivery platform for CRISPR/Cas9. Compared with viral and other vectors, EVs present several advantages, including safety, protection, capacity, penetrating ability, targeting ability and potential for modification. Consequently, EVs are profitably used to deliver the CRISPR/Cas9 in vivo. In this review, the advantages and disadvantages of the delivery form and vectors of the CRISPR/Cas9 are concluded. The favorable traits of EVs as vectors, such as the innate characteristics, physiological and pathological functions, safety and targeting ability of EVs, are summarized. Furthermore, in terms of the delivery of the CRISPR/Cas9 by EVs, EV sources and isolation strategies, the delivery form and loading methods of the CRISPR/Cas9 and applications have been concluded and discussed. Finally, this review provides future directions of EVs as vectors of the CRISPR/Cas9 system in clinical applications, such as the safety, capacity, consistent quality, yield and targeting ability of EVs.

Ferroptosis is a distinct type of programmed cell death (PCD) that depends on iron and is characterized by the accumulation of intracellular iron, exhaustion of glutathione, deactivation of glutathione peroxidase, and promotion of lipid peroxidation. Recently, accumulated investigations have demonstrated that ferroptosis is strongly correlated with the initiation and development of many lung diseases. In this review, we summarized the contribution of ferroptosis to the pathologic process of lung diseases, namely, obstructive lung diseases (chronic obstructive pulmonary disease, asthma, and cystic fibrosis), interstitial lung diseases (pulmonary fibrosis of different causes), pulmonary diseases of vascular origin (ischemia-reperfusion injury and pulmonary hypertension), pulmonary infections (bacteria, viruses, and fungi), acute lung injury, acute respiratory distress syndrome, obstructive sleep apnea, pulmonary alveolar proteinosis, and lung cancer. We also discussed the therapeutic potential of targeting ferroptosis for these lung diseases.

Extrachromosomal circular DNAs (eccDNAs) participate in tumorigenesis and tumor progression. However, the role and mechanism of eccDNAs have yet to be elucidated in non-small cell lung cancer (NSCLC). In our research, three surgically matched NSCLC tissue samples, NSCLC cell lines (H1299, A549, and H460), and a normal lung cell line (MRC-5) were used as study objects. High-throughput eccDNA sequencing and bioinformatics analysis were performed to study the distribution pattern and level of eccDNA expression. The upregulated candidate eccDNA-encoding PLCG2 was validated by routine PCR. Plasmid transfection, RNA interference, qRT‒PCR and western blotting experiments were used to verify the expression level of PLCG2. Our results showed that the chromosome distribution, length distribution, and genomic annotation of the eccDNAs were comparable between the NSCLC and normal groups. Nevertheless, there were no significant differences in eccDNAs between NSCLC tissues and matched normal lung tissues. The eccDNA derived from PLCG2 was upregulated in NSCLC cells. TCGA analysis and immunohistochemistry showed that PLCG2 was highly expressed in lung cancer tissues and tended to be associated with poor outcome. We also demonstrated that PLCG2 can promote metastasis through the regulation of mitochondrial respiration. These results suggested that PLCG2 identified by eccDNA sequencing acts as an oncogene and might be a new biomarker for NSCLC diagnosis and prognosis evaluation.

Ferroptosis is caused by the accumulation of cellular reactive oxygen species that exceed the antioxidant load that glutathione (GSH) and phospholipid hydroperoxidases with GSH-based substrates can carry When the antioxidant capacity of cells is reduced, lipid reactive oxygen species accumulate, which can cause oxidative death. Ferroptosis, an iron-dependent regulatory necrosis pathway, has emerged as a new modality of cell death that is strongly associated with cancer. Surgery, chemotherapy and radiotherapy are the main methods of cancer treatment. However, resistance to these mainstream anticancer drugs and strong toxic side effects have forced the development of alternative treatments with high efficiency and low toxicity. In recent years, an increasing number of studies have shown that traditional Chinese medicines (TCMs), especially herbs or herbal extracts, can inhibit tumor cell growth and metastasis by inducing ferroptosis, suggesting that they could be promising agents for cancer treatment. This article reviews the current research progress on the antitumor effects of TCMs through the induction of ferroptosis. The aim of these studies was to elucidate the potential mechanisms of targeting ferroptosis in cancer, and the findings could lead to new directions and reference values for developing better cancer treatment strategies.