Ferroptosis is a new form of programmed cell death due to iron-dependent excess accumulation of lipid peroxides and differs from other programmed cell deaths in morphological and biochemical characteristics. The process of ferroptosis is precisely regulated by iron metabolism, lipid metabolism, amino acid metabolism, and numerous signaling pathways, and plays a complex role in many pathophysiological processes. Recent studies have found that ferroptosis is closely associated with the development and progression of many lung diseases, including acute lung injury, pulmonary ischemia-reperfusion injury, lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Here, we present a review of the main regulatory mechanisms of ferroptosis and its research progress in the pathogenesis and treatment of lung diseases, with the aim of providing new ideas for basic and clinical research of lung-related diseases.

Purpose: To evaluate whether ferroptosis is involved in hyperoxic acute lung injury (HALI) and its mechanisms through the HALI model. Methods: HE staining was used to assess lung injury pathology after the establishment of neonatal rat HALI model. ELISA was used to detect ROS, GPX4, and GSH expression. Prussian blue staining and Western Blot were used to detect iron deposition and the expression of ferroptosis-related proteins, respectively. Results: The HALI group showed pathological changes with larger and fewer alveoli and thicker alveolar septa after HE staining. Prussian blue staining detected significant iron deposition in the lung tissue of the HALI group. GPX4, GSH, GSS, and SLC7A11 expressions were significantly decreased in the HALI group than in the normal control group. In contrast, ROS, TFRC, FHC, and FLC expressions showed opposite results (p< 0.05). Conclusion: Ferroptosis may be involved in the pathological process of hyperoxic lung injury in neonatal rats.

Purpose: Episodes of acute emotional or physical stress can have significant adverse effects on the hippocampus. Ginsenoside Rb1, the most predominant ginsenoside present in Panax species, has been reported to show a neuroprotective effect. The purpose of this study was to investigate the influence of ginsenoside Rb1 on plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels and hippocampal brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) levels in rats subjected to acute immobilization stress. Methods: Wistar rats were divided into controls treated with saline only (N), rats exposed to stress only (M), and rats pretreated with Rb1 (40 mg.kg (−1)) thirty minutes prior to stress exposure (R). In the model, animals were restrained in a plastic immobilizer for 2 h of acute immobilization stress at room temperature. ELISA was used to determine plasma levels of CORT and ACTH. The effect of Rb1 pretreatment on the expression of BDNF and TrkB was determined by immunofluorescence, real-time PCR, and Western blotting analysis. Results: The R group showed significantly increased plasma CORT and ACTH levels compared to the N and M groups. Acute stress stimulation suppressed BDNF and TrkB protein and mRNA expression in the hippocampus; otherwise, Rb1 pretreatment reversed the decreases. Conclusion: The results from this study demonstrate that Rb1 pretreatment reverses the decreases in hippocampal BDNF/TrkB and increases the plasma levels of CORT and ACTH, indicating a potential neuroprotective effect of Rb1 against acute stress.

Introduction: Electro-acupuncture (EA) can significantly improve inflammatory response, but the specific mechanism is not clear. Limb ischemia-reperfusion (I/R) first produces inflammatory reactions in the lungs. In this study, EA on Zusanli (ST36) and Sanyinjiao (SP6) were used to explore the mechanism of improving tissue inflammation by sciatic nerve disconnection. Material and Methods: A total of 56 male Sprague-Dawley rats were randomly divided into sham group, model group, EA group, SEA group, SNC+EA group, TNC+EA group and PNC+EA group. The sham groups were not given any treatment. Rats in the model group were treated with limb I/R without acupuncture intervention. In the EA group, ST36 and SP6 were given EA treatment for 30min before modeling. No electric current was given in the SEA group, and other operations were the same as those in the EA group. The SNC+EA group, TNC+EA group and PNC+EA group were respectively given sciatic nerve, tibial nerve or peroneal nerve amputation 72h before modeling, and the others were the same as the model group. Results: Compared with the sham group, PaO2 and a/A ratios decreased significantly in the model group (P < 0.05), while PA-aO2, RI, the ratio of wet to dry, lung injury value and inflammatory factor TNF-α, IL-1, IL-6, and MPO increased significantly (P < 0.05). Compared with the model group, PaO2, a/A ratios increased significantly in the EA group (P < 0.05), while PA-aO2, RI, the ratio of wet to dry lung, lung injury value, and TNF-α, IL-1, IL-6, and MPO decreased significantly (P < 0.05). After transection of the sciatic nerve, the protective effect of EA disappeared. However, when the peroneal or tibial nerve was severed, EA continued to maintain the protective effect. Conclusion: EA on ST36 and SP6 can alleviate lung injury caused by limb I/R through the sciatic nerve.

Infected wounds are common clinical injuries that often complicated by inflammation and oxidative stress due to bacterial invasion. These wounds typically suffer from impaired vascularization, which delays healing and increases the risk of complications such as sepsis and chronic wounds. Therefore, developing an effective treatment for infected wounds is highly necessary. Egg white can promote cell regeneration and repair, while chitosan is effective in resisting bacterial invasion. Sildenafil is believed to have the potential to promote angiogenesis. Based on these properties, we have prepared a new type of hydrogel using egg white and chitosan as the framework, loaded with sildenafil (CEHS). The hydrogel combines the benefits of its components, exhibiting good biocompatibility and promoting the proliferation and migration of NIH 3T3 (3T3) cells and human umbilical vein endothelial cells (HUVEC), as well as the angiogenesis in HUVEC. It also exhibits significant antioxidant, anti-inflammatory, and antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Additionally, in a mouse model of infected wounds, the CEHS effectively promoted wound healing through its excellent antioxidant and anti-inflammatory properties, antibacterial activity, and pro-angiogenic effects. In summary, this simple-to-prepare, multifunctional natural hydrogel shows great promise for the treatment of infected wounds.