Radiation pneumonitis (RP) is a prevalent and fatal complication of thoracic radiotherapy due to the lack of effective treatment options. RP primarily arises from mitochondrial injury in lung epithelial cells. The mitochondrial-derived peptide MOTS-c has demonstrated protective effects against various diseases by mitigating mitochondrial injury. C57BL/6 mice were exposed to 20 Gy of lung irradiation (IR) and received daily intraperitoneal injections of MOTS-c for 2 weeks. MOTS-c significantly ameliorated lung tissue damage, inflammation, and oxidative stress caused by radiation. Meanwhile, MOTS-c reversed the apoptosis and mitochondrial damage of alveolar epithelial cells in RP mice. Furthermore, MOTS-c significantly inhibited oxidative stress and mitochondrial damage in MLE-12 cells and primary mouse lung epithelial cells. Mechanistically, MOTS-c increased the nuclear factor erythroid 2-related factor (Nrf2) level and promoted its nuclear translocation. Notably, Nrf2 deficiency abolished the protective function of MOTS-c in mice with RP. In conclusion, MOTS-c alleviates RP by protecting mitochondrial function through an Nrf2-dependent mechanism, indicating that MOTS-c may be a novel potential protective agent against RP.

Naringenin is a natural flavanone with potent pharmacological properties. It has demonstrated therapeutic potential in treating various diseases and organ injuries, including radiation-induced lung injury (RILI). Ferroptosis is a newly type of cell death, and naringenin has been shown to attenuates ferroptosis. To evaluate the inhibitory effect and molecular mechanism of naringenin on ferroptosis during RILI process. Firstly, BEAS-2B and HUVECs cells were pre-incubated with naringenin for 1 h prior to 8 Gy of X-ray irradiation to evaluate oxidative stress, inflammation, and the mRNA levels of ferroptosis-related genes. Next, target genes of naringenin, RILI, and ferroptosis were identified using the TCMSP, SwissTargetPrediction, and GeneCards databases. The target network was constructed with Cytoscape and STRING. Finally, the core target genes were identified through in vitro experiments by qRT-PCR, western blot and immunofluorescence staining. Naringenin effectively reduced radiation-induced increasement of oxidative stress, inflammation, and ferroptosis markers in both cell lines. Network pharmacology identified 14 target genes, with prostaglandin endoperoxide synthase (PTGS2) and Valosin-containing protein (VCP) mRNA levels being prominent, which were crucial for ferroptosis regulation. Molecular docking revealed strong binding interactions between naringenin and the two target proteins. Subsequently, experimental validation confirmed that naringenin reduced the elevated levels of PTGS2 and VCP induced by radiation. Naringenin alleviates radiation-induced lung damage by inhibiting ferroptosis, with PTGS2 and VCP emerging as potential therapeutic targets.

Radiation-induced lung injury (RILI), a potentially fatal and dose-limiting complication of radiotherapy for thoracic tumors, is divided into early reversible pneumonitis and irreversible advanced-stage fibrosis. Early detection and intervention contribute to improving clinical outcomes of patients. However, there is still a lack of reliable biomarkers for early prediction and clinical diagnosis of RILI. Given the central role of inflammation in the initiation and progression of RILI, we explored specific inflammation-related biomarkers during the development of RILI in this study. Two expression profiles from the Gene Expression Omnibus (GEO) database were downloaded, in which 75 differentially expressed genes (DEGs) were screened out. Combining Gene Oncology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein–protein interaction (PPI) network analysis, we identified four inflammation-related hub genes in the progression of RILI—MMP9, IL-1β, CCR1 and S100A9. The expression levels of the hub genes were verified in RILI mouse models, with S100A9 showing the highest level of overexpression. The level of S100A9 in bronchoalveolar lavage fluid (BALF) and the expression of S100A9 in lung tissues were positively correlated with the degree of inflammation in RILI. The results above indicate that S100A9 is a potential biomarker for the early prediction and diagnosis of the development of RILI.

Objectives: This study aimed to assess the capacity of longitudinal FDG-PET radiomics for early distinguishing between locally advanced cervical cancer (LACC) patients who responded to treatment and those who did not. Methods: FDG-PET scans were obtained before and midway through concurrent chemoradiation for a study cohort of patients with LACC. Radiomics features related to image textures were extracted from the primary tumor volumes and stratified for relevance to treatment response status with the aid of random forest recursive feature elimination. Predictive models based on the k-nearest neighbors time series classifier were developed using the top-selected features to differentiate between responders and non-responders. The performance of the developed models was evaluated using receiver operating characteristic (ROC) curve analysis and n-fold cross-validation. Results: The top radiomics features extracted from scans taken midway through treatment showed significant differences between the two responder groups (p-values < 0.0005). In contrast, those from pretreatment scans did not exhibit significant differences. The AUC of the mean ROC curve for the predictive model based on the top features from pretreatment scans was 0.8529, while it reached 0.9420 for those derived midway through treatment scans. Conclusions: The study highlights the potential of longitudinal FDG-PET radiomics extracted midway through treatment for predicting response to chemoradiation in LACC patients and emphasizes that interim PET scans could be crucial in personalized medicine, ultimately enhancing therapeutic outcomes for LACC.

While a variety of wound dressing materials are available, the effective combination of multiple active components into a single composite dressing to optimize wound healing outcomes presents a substantial challenge. Herein, we introduce a novel trilayer nanofiber membrane (SNM) for accelerated infected wound healing. The SNM, fabricated via electrospinning, comprises a hydrophilic inner layer enriched with epigallocatechin-3-gallate (EGCG) for antioxidant activity, an antimicrobial middle layer incorporating silver zeolitic imidazolate framework (Ag-ZIF), and a hydrophobic outer layer of waterborne polyurethane (WPU) for structural integrity. The SNM exhibits superior mechanical properties, with a tensile strength of 8.83 ± 0.99 MPa and an elongation at break of 262.57 ± 30.06%, alongside a water vapor transmission rate (WVTR) of 521 g/m²·24h. The SNM composites demonstrate potent bactericidal effects, achieving a 93.50% ± 5.77% and 94.39% ± 4.29% reduction against E. coli and S. aureus, respectively. Furthermore, the SNM exhibits a high DPPH free radical scavenging efficiency of 95% at a concentration of 100 μg/mL. Animal studies indicate significant wound healing enhancement, with the SNM-treated group achieving a 52.78% healing rate on day 3, compared to 11.15% for the control group. This work offers a promising strategy for the development of multifunctional wound dressings with integrated antibacterial nanomaterials and natural bioactive components within a single composite material.