Ferroptosis is an iron‐dependent form of cell death caused by the inactivation of glutathione peroxidase 4 (GPX4) and accumulation of lipid peroxides. Ferroptosis has been found to participate in the ischemia‐reperfusion (I/R) injury, leading to heart dysfunction and myocardial cell death. Xanthohumol (XN), a prenylated flavonoid isolated from Humulus lupulus, has multiple pharmacological activities, such as anti‐inflammatory and antioxidant. This study is aimed at investigating whether XN could attenuate the I/R‐induced ferroptosis in cardiomyocytes and the underlying mechanisms. Cardiomyocytes were treated with Fe‐SP and RSL3, and the rat hearts were treated with I/R. The results from the present study show that XN was able to protect cardiomyocytes against Fe‐SP‐ and RSL3‐induced ferroptotic cell death by decreasing the production of lipid peroxidation and ROS, chelating iron, reducing the NRF2 protein level, and modulating the protein levels of GPX4. Moreover, XN significantly decreased the mRNA levels of ferroptosis markers, Ptgs2 and Acsl4, and the protein levels of ACSL4 and NRF2 and modulated the protein levels of GPX4 in I/R‐treated hearts. The findings from the present study suggest that XN might have the therapeutic potential for the I/R‐induced ferroptosis injury.

Myocardial ischemia/reperfusion (I/R) injury has been associated with ferroptosis, which is characterized by an iron-dependent accumulation of lipid peroxide to lethal levels. Gossypol acetic acid (GAA), a natural product taken from the seeds of cotton plants, prevents oxidative stress. However, the effects of GAA on myocardial I/R-induced ferroptosis remain unclear. This study investigated the ability of GAA to attenuate I/R-induced ferroptosis in cardiomyocytes along with the underlying mechanisms in a well-established rat model of myocardial I/R and isolated neonatal rat cardiomyocytes. H9c2 cells and cardiomyocytes were treated with the ferroptosis inducers erastin, RSL3, and Fe-SP. GAA could protect H9c2 cells against ferroptotic cell death caused by these ferroptosis inducers by decreasing the production of malondialdehyde and reactive oxygen species, chelating iron content, and downregulating mRNA levels of Ptgs2. GAA could prevent oxygen-glucose deprivation/reperfusion-induced cell death and lipid peroxidation in the cardiomyocytes. Moreover, GAA significantly attenuated myocardial infarct size, reduced lipid peroxidation, decreased the mRNA levels of the ferroptosis markers Ptgs2 and Acsl4, decreased the protein levels of ACSL4 and NRF2, and increased the protein levels of GPX4 in I/R-induced ex vivo rat hearts. Thus, GAA may play a cytoprotectant role in ferroptosis-induced cardiomyocyte death and myocardial I/R-induced ferroptotic cell death.

Objectives: Cardiovascular diseases are one of the primary causes of death. Cardiomyocyte loss is a significant feature of cardiac injury. Ferroptosis is iron-dependent cell death, which occurs due to excess iron and reactive oxygen species (ROS) accumulation causing lipid peroxidation, and subsequent cell death. Ferroptosis has been confirmed to mediate ischemia/reperfusion-induced cardiomyopathy and chemotherapy-induced cardiotoxicity. Berberine (BBR) has been proven to protect the heart from cardiomyopathies, including cardiac hypertrophy, heart failure, myocardial infarction, and arrhythmias. It protects cardiomyocytes from apoptosis and autophagy. However, the relation between BBR and ferroptosis is still unknown. This study aimed to confirm if BBR reduces cardiac cell loss via inhibiting ferroptosis. Materials and Methods: We used erastin and Ras-selective lethal small molecule 3 (RSL3) to establish a ferroptosis model in an H9c2 cardiomyoblast cell line and rat neonatal cardiomyocytes to prove that BBR has a protective effect on cardiac cells via inhibiting ferroptosis. Results: In H9c2 cardiomyoblasts, the results showed that BBR reduced erastin and RSL3-induced cell viability loss. Moreover, BBR decreased ROS accumulation and lipid peroxidation in cells induced with ferroptosis. Furthermore, quantitative polymerase chain reaction results showed that Ptgs2 mRNA was reduced in BBR-treated cells. In rat neonatal cardiomyocytes, BBR reduced RSL3-induced loss of cell viability. Conclusion: These results indicated that BBR inhibited ferroptosis via reducing ROS generation and reducing lipid peroxidation in erastin and RSL3-treated cardiac cells.

Using bacteriophages (phages) as environmental sanitizers has been recognized as a potential alternative method to remove bacterial contamination in vitro; however, very few studies are available on the application of phages for infection control in hospitals. Here, we performed a 3-year prospective intervention study using aerosolized phage cocktails as biocontrol agents against carbapenem-resistant Acinetobacter baumannii (CRAB) infection in the hospital. When a CRAB-infected patient was identified in an intensive care unit (ICU), their surrounding environment was chosen for phage aerosol decontamination. Before decontamination, 501 clinical specimens from the patients were subjected to antibiotic resistance analysis and phage typing. The optimal phage cocktails were a combination of different phage families or were constructed by next-evolutionary phage typing with the highest score for the host lysis zone to prevent the development of environmental CRAB phage resistance. The phage infection percentage of the antibiotic-resistant A. baumannii strains was 97.1%, whereas the infection percentage in the antibiotic-susceptible strains was 79.3%. During the phage decontamination periods from 2017 to 2019, the percentage of carbapenem-resistant A. baumannii in test ICUs decreased significantly from 65.3% to 55%. The rate of new acquisitions of CRAB infection over the three years was 4.4 per 1000 patient-days, which was significantly lower than that in the control wards (8.9 per 1000 patient-days) where phage decontamination had never been performed. In conclusion, our results support the potential of phage cocktails to decrease CRAB infection rates, and the aerosol generation process may make this approach more comprehensive and time-saving.

Phage-based decontamination has rarely been explored in real-world settings, particularly in the environments of patients undergoing extracorporeal membrane oxygenation (ECMO). This four-year prospective study aimed to evaluate the effectiveness of aerosolized phage cocktails tailored to combat target antibiotic-resistant species of Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. The decontamination procedure with phage aerosols was proactively implemented before the admission of ECMO patients based on a thorough analysis of phage typing results from bacterial species isolated from prospective patient areas during the preceding two months. The phage cocktail formulation design also accounted for phage resistance development, phage families, and plaque characteristics. Throughout the study, 85 ECMO patients were monitored, with the environments of 22 patients undergoing phage decontamination. Fifty phage cocktails were prepared to target the identified species. Respiratory infections were most common among ECMO patients, accounting for 71.4 %. The ECMO duration for patients infected with the targeted species was significantly longer than that for noninfected patients (P = 0.019), with peak infection incidence occurring between 3 and 7 days of ECMO treatment (67.1 per 1000 ECMO days). Notably, none of the patients in phage-treated environments contracted infections from the targeted species. However, the overall incidence of bacterial infections did not significantly correlate with phage decontamination efforts, as phages are effective only against their specific hosts. This study demonstrates the potential of prophylactic phage decontamination to prevent specific infections, aligning with One Health principles by offering a sustainable alternative to antibiotics, potentially significantly reducing antibiotic use.