Ming Mao

Acute respiratory distress syndrome (ARDS) gives rise to uncontrolled inflammatory response and oxidative stress, causing very high mortality globally. Pomiferin is a kind of prenylated isoflavonoid extracted from Maclura pomifera, owning anti‐inflammatory and antioxidant properties. However, the functions and possible mechanisms of pomiferin in lipopolysaccharide‐ (LPS‐) induced ARDS remain unknown. C57BL/6 mice were injected with LPS (5 mg/kg) intratracheally to induce an in vivo ARDS model while RAW264.7 macrophages were stimulated with LPS (100 ng/ml) to induce an in vitro model. Our data demonstrated that pomiferin (20 mg/kg) significantly improved pulmonary function and lung pathological injury in mice with ARDS, apart from increasing survival rate. Meanwhile, pomiferin treatment also inhibited LPS‐induced inflammation as well as oxidative stress in lung tissues. LPS stimulation significantly activated AKT/Foxo1 signal pathway in lung tissues, which could be reversed after pomiferin treatment. In vitro experiments further showed that 10, 20, and 50 μM of pomiferin could enhance cell viability of RAW264.7 macrophages stimulated with LPS. What is more, 3‐deoxysappanchalcone (3‐DE), one AKT agonist, was used to active AKT in RAW264.7 macrophages. The results further showed that 3‐DE could abolish pomiferin‐elicited protection in LPS‐treated RAW264.7 macrophages, evidenced by activated inflammation and oxidative stress. Taken together, our study showed that pomiferin could exert an ARDS‐protective effect by blocking the AKT/Foxo1 signal pathway to inhibit LPS‐induced inflammatory response and oxidative injury, which may serve as a potential candidate for the treatment of ARDS in the future.

Background: Ferroptosis is essential to regulate tumor growth and serves as a promising therapeutic target to lung cancer. Ubiquitin‐specific protease 35 (USP35) belongs to the deubiquitinases family that is associated with cell proliferation and mitosis. In this research, we aim to elucidate the potential role and molecular basis of USP35 in lung cancer.Methods: Lung cancer cells were infected with lentiviral vectors to silence or overexpress USP35. Cell viability, colony formation, lipid reactive oxygen species production, intracellular iron metabolism, and other ferroptotic markers were detected. The role of USP35 on ferroptosis and tumor progression were also tested in mouse tumor xenograft models in vivo.Results: USP35 was abundant in human lung cancer tissues and cell lines. USP35 knockdown promoted ferroptosis, and inhibited cell growth, colony formation, and tumor progression in lung cancer cells. USP35 overexpression did not affect tumorigenesis and ferroptosis under basal conditions, but reduced erastin/RSL3‐triggered iron disturbance and ferroptosis, thereby facilitating lung cancer cell growth and tumor progression. Further studies determined that USP35 directly interacted with ferroportin (FPN) and functioned as a deubiquitinase to maintain its protein stability. More importantly, we observed that USP35 knockdown sensitized lung cancer cells to cisplatin and paclitaxel chemotherapy.Conclusion: USP35 modulates ferroptosis in lung cancer via targeting FPN, and it is a promising therapeutic target to lung cancer.