Lung adenocarcinoma (LUAD) is the most ordinary histological subtype of lung cancer, and regulatory cell death is an attractive target for cancer therapy. Recent reports suggested that cuproptosis is a novel copper-dependent modulated form of cell death dependent on mitochondrial respiration. However, the role of cuproptosis-related genes (CRGs) in the LUAD process is unclear. In the current study, we found that DLD, LIAS, PDHB, DLAT and LIPA1 in 10 differentially expressed CRGs were central genes. GO and KEGG enrichment results showed that these 10 CRGs were mainly enriched in acetyl-CoA biosynthetic process, mitochondrial matrix, citrate cycle (TCA cycle) and pyruvate metabolism. Furthermore, we constructed a prognostic gene signature model based on the six prognostic CRGs, which demonstrated good predictive potential. Excitedly, we found that these six prognostic CRGs were significantly associated with most immune cell types, with DLD being the most significant (19 types). Significant correlations were noted between some prognostic CRGs and tumor mutation burden and microsatellite instability. Clinical correlation analysis showed that DLD was related to the pathological stage, T stage, and M stage of patients with LUAD. Lastly, we constructed the lncRNA UCA1/miR-1-3p/DLD axis that may play a key role in the progression of LUAD and screened nine active components of traditional Chinese medicine (TCM) that may regulate DLD. Further, in vitro cell experiments and molecular docking were used to verify this. In conclusion, we analyzed the potential value of CRGs in the progression of LUAD, constructed the potential regulatory axis of ceRNA, and obtained the targeted regulatory TCM active ingredients through comprehensive bioinformatics combined with experimental validation strategies. This work not only provides new insights into the treatment of LUAD but also includes a basis for the development of new immunotherapy drugs that target cuproptosis.

Isobavachalcone (IBC), also known as isobapsoralcone, is a natural flavonoid widely derived from many medicinal plants, including Fabaceae, Moraceae, and so forth. IBC has been paid more and more attention by researchers in recent years due to its pharmacological activity in many diseases. This review aims to describe in detail the plant sources, pharmacokinetics, toxicity, pharmacological activities, and molecular mechanisms of IBC on various diseases. We found that IBC can be obtained not only by extraction but also by chemical synthesis. Pharmacokinetic studies have shown that IBC has low bioavailability, but can penetrate the blood–brain barrier and is widely distributed in the brain. Its pharmacological activities mainly include anticancer, antibacterial, anti‐inflammatory, antiviral, neuroprotective, bone protection, and other activities. In particular, IBC shows strong anti‐tumor and anti‐inflammatory therapeutic potential due to its anti‐cancer and anti‐inflammatory activities. However, due to its hepatotoxicity, there may be more drug interactions. Therefore, more and more in‐depth studies are needed for its clinical application. Mechanically, IBC can induce the production of reactive oxygen species (ROS), inhibit AKT, ERK, and Wnt pathways, and promote apoptosis of cancer cells through mitochondrial or endoplasmic reticulum pathways. IBC can inhibit the NF‐κB pathway and the production of multiple inflammatory mediators by activating NRF2/HO‐1 pathway, thus producing anti‐inflammatory effects. Moreover, we discussed the limitations of current research on IBC and put forward some new perspectives and challenges, which provide a strong basis for clinical application and new drug development of IBC in the future.

Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, and radiotherapy. However, due to the strong metastatic characteristics of lung cancer and the emergence of related drug resistance and radiation resistance, the overall survival rate of lung cancer patients is not ideal. There is an urgent need to develop new treatment strategies or new effective drugs to treat lung cancer. Ferroptosis, a novel type of programmed cell death, is different from the traditional cell death pathways such as apoptosis, necrosis, pyroptosis and so on. It is caused by the increase of iron-dependent reactive oxygen species due to intracellular iron overload, which leads to the accumulation of lipid peroxides, thus inducing cell membrane oxidative damage, affecting the normal life process of cells, and finally promoting the process of ferroptosis. The regulation of ferroptosis is closely related to the normal physiological process of cells, and it involves iron metabolism, lipid metabolism, and the balance between oxygen-free radical reaction and lipid peroxidation. A large number of studies have confirmed that ferroptosis is a result of the combined action of the cellular oxidation/antioxidant system and cell membrane damage/repair, which has great potential application in tumor therapy. Therefore, this review aims to explore potential therapeutic targets for ferroptosis in lung cancer by clarifying the regulatory pathway of ferroptosis. Based on the study of ferroptosis, the regulation mechanism of ferroptosis in lung cancer was understood and the existing chemical drugs and natural compounds targeting ferroptosis in lung cancer were summarized, with the aim of providing new ideas for the treatment of lung cancer. In addition, it also provides the basis for the discovery and clinical application of chemical drugs and natural compounds targeting ferroptosis to effectively treat lung cancer.

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