Radiotherapy is a prevalent treatment modality for thoracic tumors; however, it can lead to radiation-induced lung injury (RILI), which currently lacks effective interventions. ACT001, a prodrug of micheliolide, has demonstrated promising clinical application potential, yet its impact on RILI requires further validation. This study aims to investigate the radioprotective effects of ACT001 on RILI and elucidate its underlying mechanism. Sprague-Dawley rats were utilized to induce RILI following 20 Gy X-ray chest irradiation, and lung tissue inflammation and fibrosis were assessed using hematoxylin and eosin (H&E) and Masson staining. Lung injury, inflammation, and oxidative stress markers were evaluated employing commercial kits. Pyroptosis-related differentially expressed genes (DEGs) were analyzed using a microarray dataset from the Gene Expression Omnibus (GEO) database, and their functions and hub genes were identified through protein-protein interaction networks. Pyroptosis-related genes were detected via RT-qPCR, western blotting, immunofluorescence, and immunohistochemistry. The results demonstrated that ACT001 ameliorated RILI, diminished pro-inflammatory cytokine release and fibrosis, and mitigated the activation of the NLRP3 inflammasome while inhibiting pyroptosis in lung tissue. In conclusion, our study reveals that ACT001 can suppress NLRP3 inflammasome-mediated pyroptosis and improve RILI, suggesting its potential as a novel protective agent for RILI.

Radiation-induced brain injury (RIBI) is a significant challenge in radiotherapy for head and neck tumors, impacting patients' quality of life. In exploring potential treatments, this study focuses on memantine hydrochloride and hydrogen-rich water, hypothesized to mitigate RIBI through inhibiting the NLRP3/NLRC4/Caspase-1 pathway. In a controlled study involving 40 Sprague-Dawley rats, divided into five groups including a control and various treatment groups, we assessed the effects of these treatments on RIBI. Post-irradiation, all irradiated groups displayed symptoms like weight loss and salivation, with notable variations among different treatment approaches. Particularly, hydrogen-rich water showed a promising reduction in these symptoms. Histopathological analysis indicated substantial hippocampal damage in the radiation-only group, while the groups receiving memantine and/or hydrogen-rich water exhibited significant mitigation of such damage. Molecular studies, revealed a decrease in oxidative stress markers and an attenuated inflammatory response in the treatment groups. Immunohistochemistry further confirmed these molecular changes, suggesting the effectiveness of these agents. Echoing recent scientific inquiries into the protective roles of specific compounds against radiation-induced damages, our study adds to the growing body of evidence on the potential of memantine and hydrogen-rich water as novel therapeutic strategies for RIBI.

The Official Journal of EuroPCR and the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Objective: This study aimed to analyze the disease burden and risk factors of nasopharyngeal carcinoma (NPC) in China in 2019, assessing trends from 1990 to 2019 to inform prevention and treatment. Methods: Utilizing the Global Burden of Disease Study 2019 (GBD 2019) Data, a descriptive analysis method was employed to analyze the disease burden and risk factors for NPC in China in 2019. Additionally, the disease burden of NPC in China from 1990 to 2019 was examined. The Joinpoint Regression Program was used to estimate the annual percent change (APC) and the average APC (AAPC). Results: From 1990 to 2019, the number of new NPC cases in China increased from 47.49% to 62.57% of the global NPC cases, and the proportion of prevalence in China to the world rose from 45.29% to 70.81%. The total change rates of the age-standardized incidence rate (ASIR) globally and in China were 36.77% and 70.69%, respectively. The total change rates of the age-standardized prevalence rate (ASPR) globally and in China were 115.34% and 232.52%, respectively. The increase in ASIR and ASPR in China was significantly higher than the global average. The decrease in age-standardized death rate, standardized disability-adjusted life years rate, and standardized years of life lost due to premature mortality rate in China was much more pronounced than globally. From 1990 to 2019, the ASIR and ASPR in China showed an upward trend, with AAPCs of 1.80% and 4.19%, respectively. Over the past 30 years, the incidence among young and middle-aged individuals in China has increased, indicating a trend toward younger age at onset. In all periods, the risk of incidence, prevalence, and death in males was significantly higher than in females. Conclusion: In summary, the disease burden of NPC in China remains significant. Therefore, continued attention and strengthening of risk factor control, along with strategies for early diagnosis and treatment, are essential.

Excessive manganese (Mn) exposure is associated with neuroinflammation and cognitive impairment, yet the contribution of endogenous pro-resolving pathways to Mn neurotoxicity remains incompletely understood. Here, we examined the involvement of the lipocalin-type prostaglandin D synthase (L-PGDS)/15-deoxy-Δ^12,14-prostaglandin J2 (15d-PGJ2) pathway using Mn-treated male C57BL/6J mice, BV2 microglia, and SH-SY5Y neurons, together with data from occupationally Mn-exposed workers (cross-sectional, hypothesis-generating). In the occupational cohort, circulating 15d-PGJ2 levels and L-PGDS expression were reduced following Mn exposure, consistent with the experimental findings. PPI network analysis and promoter prediction highlighted C/EBPβ and MMP9 as potential mediators of Mn-induced neuroinflammatory responses. Consistent with these observations, Mn exposure increased C/EBPβ and MMP9 expression, promoted M1 microglial polarization, elevated ROS production, and aggravated neuronal injury in a microglia–neuron co-culture system. Knocking down either C/EBPβ or MMP9 attenuated inflammatory activation and oxidative stress and reduced neuronal damage. Administration of exogenous 15d-PGJ2 suppressed Mn-induced increases in C/EBPβ and MMP9, alleviated inflammatory and oxidative responses, and partially ameliorated cognitive impairment in Mn-exposed mice. Transcriptomic analyses further showed that 15d-PGJ2 counteracted a substantial proportion of Mn-induced transcriptional alterations, particularly those related to inflammatory and neurodevelopmental processes. In addition, Ptgds knockdown reduced endogenous 15d-PGJ2 production and increased MMP9 expression, whereas exogenous 15d-PGJ2 largely reversed these changes. Together, these findings support the involvement of L-PGDS/15d-PGJ2 pathway dysregulation in Mn-induced neuroinflammation and suggest that restoration of 15d-PGJ2 signaling may represent a potential therapeutic approach for Mn-associated neurotoxicity.

Hydrogen-rich water (HRW) has shown neuroprotective effects in acute brain injury, but its role in chronic radiation-induced brain injury (RIBI) remains unclear. This study investigated the long-term efficacy of HRW in mitigating cognitive impairment and neuronal damage caused by chronic RIBI. Fifty male Sprague Dawley rats were randomly divided into five groups: control, irradiation (IR), IR with memantine, IR with HRW, and IR with combined treatment. All but the control group received 20 Gy whole-brain X-ray irradiation, followed by daily interventions for 60 days. Behavioral assessments, histopathological analyses, oxidative stress measurements, ¹⁸F-FDG PET/CT imaging, transcriptomic sequencing, RT-qPCR, Western blot, and serum ELISA were performed. HRW significantly improved anxiety-like behavior, memory, and learning performance compared to the IR group. Histological results revealed that HRW reduced neuronal swelling, degeneration, and loss and enhanced dendritic spine density and neurogenesis. PET/CT imaging showed increased hippocampal glucose uptake in the IR group, which was alleviated by HRW treatment. Transcriptomic and molecular analyses indicated that HRW modulated key genes and proteins, including CD44, CD74, SPP1, and Wnt1, potentially through the MIF, Wnt, and SPP1 signaling pathways. Serum CD44 levels were also lower in treated rats, suggesting its potential as a biomarker for chronic RIBI. These findings demonstrate that HRW can alleviate chronic RIBI by preserving neuronal structure, reducing inflammation, and enhancing neuroplasticity, supporting its potential as a therapeutic strategy for radiation-induced cognitive impairment.